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1. Dosimetric comparison between VMAT and tomotherapy with para-aortic radiation for cervix carcinoma

Author: Oldrini, S., Guinement, L., Salleron, J., Brunaud, C., Huger, S., Grandgirard, N., Villani, N., Marchesi, V., Oldrini, G., Peiffert, D., Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Cancer du col utérin, Irradiation lomboaortique, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Tomothérapie, RCMI
Abstract: International audience; Objectif de l’étudeLa radiothérapie conformationnelle avec modulation d’intensité (RCMI) pour les cancers du col utérin a prouvé sa supériorité dosimétrique en termes de toxicité digestive, comparativement à la radiothérapie conformationnelle non modulée. L’arcthérapie volumétrique modulée a montré son intérêt dosimétrique comparativement à la RCMI à faisceaux statiques. L’objectif de notre étude était de comparer arcthérapie volumétrique modulée et tomothérapie pour des cancers du col utérin avec irradiation lomboartique.Patientes et méthodesLes dosimétries à 45 Gy de dix patientes ont été comparées entre les deux techniques (arcthérapie volumétrique modulée et tomothérapie) ainsi qu’avec la radiothérapie conformationnelle non modulée, avec recueil de la dose reçue par les volumes cibles prévisionnels, les reins, l’intestin, le rectum, la vessie, la moelle osseuse et la moelle épinière, ainsi que la dose intégrale.RésultatsUne différence significative a été observée en faveur de l’arcthérapie volumétrique modulée et de la tomothérapie sur la radiothérapie conformationnelle non modulée pour l’épargne intestinale (volumes recevant respectivement 20, 30 et 45 Gy : V20 Gy, V30 Gy et V45 Gy), rectale (V30 Gy et V45 Gy), vésicale (V30 Gy et V45 Gy) et rénale (volume recevant 12 Gy [V12 Gy], dose moyenne, V20 Gy). Les volumes recevant 20, 30 et 45 Gy étaient significativement plus grands avec la radiothérapie conformationnelle non modulée qu’avec l’arcthérapie volumétrique modulée et la tomothérapie. La différence était en faveur de la tomothérapie comparativement à l’arcthérapie volumétrique modulée pour le V12 Gy des reins et le V45 Gy de la vessie.ConclusionCette étude confirme l’intérêt des techniques d’arcthérapie volumétrique modulée et de tomothérapie pour l’irradiation pelvienne et lomboaortique des cancers du col comparativement à la radiothérapie conformationnelle non modulée. Il y avait peu de différence entre l’arcthérapie volumétrique modulée et la tomothérapie, en dehors d’une meilleure épargne rénale avec la tomothérapie, ce qui peut être intéressant pour des patientes recevant des chimiothérapies néphrotoxiques.
Published: 2015

2. Etat des lieux des tests RAS chez les patients atteints de cancer colorectal métastatique en 2014

Author: Sabourin , Jean-Christophe, Merlin , Jean-Louis, Lièvre , Astrid, Ducreux , Michel, Artru , Pascal, Seronde , Audrey, Gicquel , Corinne, Laurent-Puig , Pierre, CHU Rouen, Normandie Université (NU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Hôpital privé Jean Mermoz, Merck Serono, Merck & Co. Inc, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Hôpital Européen Georges Pompidou [APHP] ( HEGP )
Subjects: [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Abstract: Présentation Poster; National audience; Introduction : De 2008 à 2013, la prescription des anticorps monoclonaux anti-EGFR (cetuximab et panitumumab) dans le cancer colorectal métastatique (CCRm) était soumise à la mise en évidence préalable de l’absence de mutation somatique de l’exon 2 du gène KRAS, dont l’impact sur l’efficacité thérapeutique avait été démontré. En 2013, l’identification d’autres mutations sur les exons 3, 4 du gène KRAS et 2, 3, 4 du gène NRAS exerçant un effet similaire, et la restriction de la prescription du cetuximab aux patients atteints de CCRm non porteurs d’une de ces mutations dites « mutations RAS » a permis d’affiner davantage la population susceptible de bénéficier de ce traitement.Objectifs et méthode : L’étude FLASH-RAS fait suite à l’étude FLASH-KRAS qui a permis de décrire les pratiques de prescription et de réalisation du test KRAS exon 2 en 2011. FLASH-RAS est une étude observationnelle rétrospective nationale multicentrique dont l’objectif principal était l’évaluation en 2014 des pratiques de prescription et de réalisation des tests RAS dans la prise en charge (PEC) du CCRm. Les objectifs secondaires étaient de décrire l’évolution des taux de prescription des tests RAS entre 2011 et 2014, de décrire le circuit et le délai d’obtention des résultats, d’analyser leur impact sur la stratégie thérapeutique.Résultats : 375 patients atteints d’un CCRm diagnostiqué après le 1er mars 2014 et pour lesquels un traitement de 1ère ligne métastatique a été instauré entre le 1er mars et le 30 juin 2014 ont été analysés. 90.1% (IC95%= [87.1% ; 93.2%]) d’entre eux ont bénéficié d’une demande de test RAS lors de leur PEC en 1ère ligne métastatique, un taux en augmentation significative par rapport à 2011 (81.1% dans FLASH-KRAS, p
Published: 2015

3. Suivi après radiothérapie d’un cancer du canal anal

Author: N, Meillan, F, Huguet, D, Peiffert, Service d’Oncologie-Radiothérapie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), Service d'oncologie-radiothérapie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: Decision Trees, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Anus Neoplasms, Anal carcinoma: Aftercare: Positron emission tomography, Carcinome épidermoïde du canal anal, Endosonography, Tomographie par émission de positons, Magnetic resonance imaging, Imagerie par résonance magnétique, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Suivi post-thérapeutique, Échoendocopie endorectale, Follow-Up Studies
Abstract: International audience; Anal canal carcinoma is a rare and curable disease for which the standard of care is radiation therapy with concurrent 5-fluoro-uracil and mitomycine-based chemotherapy. Post-treatment follow-up however is rather poorly defined. This article offers a review of the various post-treatment surveillance options both for early diagnosis of relapse and care for late treatment effects. While follow-up remains mostly clinical, we will discuss morphologic (endorectal echoendoscopy, pelvic magnetic resonance imaging, tomodensitometry and positron emission tomography) and biologic (squamous cell carcinoma antigen and pathology) follow-up so as to determine their diagnostic and prognostic value.; Le carcinome épidermoïde du canal anal est une maladie rare et souvent curable dont le traitement standard repose sur la radiothérapie en association avec une chimiothérapie à base de 5-fluoro-uracile et de mitomycine-C. La surveillance après ce traitement reste cependant mal codifiée. L’objectif de cet article est de proposer une mise au point sur les différentes modalités de surveillance après traitement à la recherche de rechute ou d’effets secondaires. Si cette surveillance est essentiellement clinique, nous évoquerons les différentes perspectives de surveillance morphologique (échoendoscopie endorectale, imagerie par résonance magnétique pelvienne, tomodensitométrie et tomographie par émission de positons) ainsi que biologique (squamous cell carcinoma antigen et histologie) et leur apport diagnostique et pronostique.
Published: 2015

4. Évaluation nationale de l’enseignement théorique du troisième cycle des études médicales en France

Author: Faivre , J.-C., Agopiantz , M., Loeb , E., Cassinari , K., Wack , M., Catoire , P., Braun , M., Thilly , N., Coudane , H., Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, InterSyndicale Nationale des Internes (ISNI), Université de Lorraine (UL), Service d'Endocrinologie et Gynécologie Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de psychiatrie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rouen Normandie (UNIROUEN), CHU Rouen, Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Université de Lille, Droit et Santé, Association nationale des étudiants en médecine de France (ANEMF), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Service de Médecine Légale [CHRU Nancy], Conférence internationale des doyens des facultés de médecine d'expression française, Laboratoire de psychologie de l'interaction et des relations intersubjectives (INTERPSY), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), InterSyndicale Nationale des Internes ( ISNI ), Université de Lorraine ( UL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Service de psychiatrie [Caen], Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Université de Rouen Normandie ( UNIROUEN ), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R ), Association nationale des étudiants en médecine de France ( ANEMF ), Imagerie Adaptative Diagnostique et Interventionnelle ( IADI ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Laboratoire de psychologie de l'interaction et des relations intersubjectives ( INTERPSY ), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Medical education, Faculty, Medical, Students, Medical, Education, Medical, Teaching, Internship and residency, Internat, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Personal Satisfaction, Études médicales, Quality assurance, Troisième cycle, Surveys and Questionnaires, Évaluation, Humans, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Curriculum, France, Enseignement
Abstract: International audience; ObjectivesIn France, medical students regularly complain about the shortcomings of their theoretical training and the necessity of its adaptation to better fit the needs of students. The goal was to evaluate the theoretical teaching practices in postgraduate medical studies by: 1) collecting data from medical students in different medical faculties in France; 2) comparing this data with expected practices when it is possible; 3) and proposing several lines of improvement.MethodsA survey of theoretical practices in the 3rd cycle of medical studies was conducted by self-administered questionnaires which were free of charge, anonymous, and administered electronically from July 3 to October 31, 2013 to all medical students in France.ResultsNational, inter-regional, regional and field internship educational content was absent in respectively 50.5%, 42.8%, 26.0% and 30.2% of cases. Medical students follow complementary training due to insufficient DES and/or DESC 2 training in 43.7% of cases or as part of a professional project in 54.9% of cases. The knowledge sought by medical students concerns the following crosscutting topics: career development (58.9%), practice management (50.7%), medical English (50.4%) and their specialty organization (49.9%). Fifty-four point one percent would like to be evaluated on their theoretical training on an annual basis.ConclusionThe results of this first national survey give insights into the theoretical teaching conditions in postgraduate medical education in France and the aspirations of medical students.; ProposLe troisième cycle des études médicales (TCEM) constitue la base de la formation spécialisée des médecins en France. L’objectif a été d’évaluer les pratiques d’enseignement théorique au cours du troisième cycle des études médicales en : 1) recueillant des données auprès des internes en médecine dans les différentes facultés de France ; 2) comparant ces données aux pratiques opposables quand cela était possible ; 3) et en proposant des mesures d’amélioration.MéthodesUne enquête sur les pratiques d’enseignement théorique en TCEM a été réalisée par auto-questionnaire, libre et anonyme, administré par voie électronique du 3 juillet au 31 octobre 2013 à l’ensemble des étudiants en TCEM de France.RésultatsLes enseignements nationaux, inter-régionaux, régionaux et sur le terrain de stage n’existent pas dans respectivement 50,5 %, 42,8 %, 26,0 % et 30,2 % des cas. Les internes ont recours à des formations complémentaires en raison d’une formation de DES et/ou DESC 2 jugée insuffisante (43,7 %) ou dans le cadre d’un projet professionnel (54,9 %). Les thématiques transversales à développer étaient le développement de carrière (58,9 %), la gestion d’un cabinet ou d’un service (50,7 %), l’anglais médical (50,4 %) et l’organisation de leur spécialité (49,9 %). Ils souhaiteraient pour 54,1 % d’entre eux être évalués annuellement sur le plan théorique.ConclusionIl s’agit de la première évaluation nationale du TCEM en France sur le versant de l’enseignement théorique. Complétée par le versant pratique, elle pourrait permettre de proposer une réforme du TCEM capable d’accroître l’efficience de la formation, sans allongement de sa durée.
Published: 2015

5. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

Author: Julie, Vincent, Christophe, Mariette, Denis, Pezet, Emmanuel, Huet, Franck, Bonnetain, Olivier, Bouché, Thierry, Conroy, Bernard, Roullet, Jean-François, Seitz, Jean-Philippe, Herr, Frédéric, Di Fiore, Jean-Louis, Jouve, Laurent, Bedenne, M, Ducreux, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie digestive [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital privé Sainte-Marie - Ramsay Générale de Santé, Hôpital Charles Nicolle [Rouen], Butel J, Desselle P, Brice JC, Tissot B, Votte-Lambert A, Joly J, Burtin P, Arnaud JP, Cellier P, Estermann F, Chauvet B, Maringe E, Ozanne F, Varlet F, Becouarn Y, Avril A, Rougier P, Nordlinger B, Vincendet M, Charneau J, Pillon D, Stremsdoerfer N, Pelletier M, Clavero-Fabri MC, Leduc B, Segol P, Argouach LP, Roussel A, Maurel J, Salame R, Lacourt J, Janoray P, Ruget O, Baudet-Klepping D, Dupont G, Bommelaer G, Ruszniewski P, Hammel P, Chaussade S, Dousset B, Denis B, Wagner JD, Tamby E, Petit T, Weiss AM, Barbare JC, Jouve JL, Phelip JM, Senesse P, Michiels C, Maingon P, Coudert B, Fraisse J, Queuniet A, Gasnault L, Gstach JH, Guichard B, Howaizi M, Geoffroy P, Picot C, Fournet J, Mousseau M, Stampfli C, Michel P, Doll J, Durand S, Buffet C, Triboulet JP, Denimal F, Hebbar M, Quandalle P, Mirabel X, Lledo G, Giovannini M, Souillac P, Untereiner M, Leroy-Terquem E, Lacroix H, Francois E, Lagasse JP, Breteau N, Legoux JL, Etienne JC, Delattre JF, Lubrano D, Levy-Chazal N, Palot JP, Nasca S, Demange L, Nguyen TD, Seng S, Michel P, Teniere P, Thevenet P, Le Brise H, Fleury J, Kammerer J, Cosme H, Novello P, Avignon JP, Berton C, Legueul, Parisot P, Aunis G, Vetter D, Platini C, Cals L, Rouhier D, Robin B, Champetier T, Cartalat A, Marchal C, Guillemin F, Flamenbaum M, Cassan D, Ducreux M., Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU - HÔTEL-DIEU Clermont-Ferrand, Service de chirurgie digestive [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU de Poitiers, and Hôpital de la Timone [CHU - APHM] ( TIMONE )
Subjects: Male, Cancer Research, Time Factors, Esophageal Neoplasms, Kaplan-Meier Estimate, MESH: Esophagectomy, law.invention, MESH: Proportional Hazards Models, MESH : Adenocarcinoma, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, MESH : Esophagectomy, MESH: Risk Factors, MESH : Neoplasm Staging, MESH : Female, MESH : Carcinoma, Squamous Cell, MESH: Treatment Outcome, MESH: Chemoradiotherapy, Randomised controlled trial, education.field_of_study, Hazard ratio, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carcinoma, Squamous Cell, Chemoradiotherapy, MESH : Chemoradiotherapy, MESH: Neoplasm Staging, MESH : Risk Factors, Neoadjuvant Therapy, 3. Good health, Oesophageal neoplasms, Treatment Outcome, Oncology, Chemoradiation, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, Carcinoma, Squamous Cell, 030211 gastroenterology & hepatology, Female, Esophageal Squamous Cell Carcinoma, France, MESH : Time Factors, medicine.medical_specialty, MESH: Radiotherapy, Adjuvant, MESH : Male, Population, MESH: Neoadjuvant Therapy, Locally advanced, MESH : Treatment Outcome, Adenocarcinoma, MESH : Radiotherapy, Adjuvant, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Early surgery, medicine, Humans, Basal cell, Salvage surgery, education, MESH : France, Contraindication, MESH: Kaplan-Meier Estimate, Neoplasm Staging, Proportional Hazards Models, MESH: Humans, business.industry, MESH : Humans, MESH: Adenocarcinoma, MESH: Time Factors, Cancer, medicine.disease, MESH : Proportional Hazards Models, MESH: Male, Surgery, Esophagectomy, MESH: France, Radiotherapy, Adjuvant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Esophageal Neoplasms, business, MESH : Neoadjuvant Therapy, MESH: Female
Abstract: International audience; BACKGROUND:Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.METHODS:Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FINDINGS:Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p
Published: 2015

6. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Author: J.-L. Van Laethem, Dirk Arnold, Thomas Seufferlein, Caroline Caramella, A. Sa. Cuhna, Antoine Hollebecque, Michel Ducreux, Thierry Conroy, Diane Goéré, Karin Haustermans, Pascal Burtin, Université Paris-Sud 11 - Faculté de médecine ( UP11 UFR Médecine ), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Imagerie diagnostique (radiologie / échographie), Département d'imagerie médicale [Gustave Roussy], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] ( DITEP ), Institut Gustave Roussy ( IGR ), Département de chirurgie générale [Gustave Roussy], Universitätsklinikum Ulm, University Hospitals Leuven [Leuven], Hôpital Erasme (Bruxelles), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), Cervantes A, Pentheroudakis G, Pavlidis N, Stahel RA, Cardoso F, Senkus-Konefka E, Arnold D, Horwich A, Sessa C, Colombo N, Licitra L, Buske C, Ladetto M, Peters S, Blay JY, Keilholz U, Strasser F, Hassan AA, Herrstedt J, McGregor KH, Bramley C, Lamarre J, Wallace M, Galli A, Je S., Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Universitätsklinikum Ulm - University Hospital of Ulm, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: Oncology, medicine.medical_specialty, MESH: Combined Modality Therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, medicine, MESH : Pancreas, ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, General surgery, MESH : Humans, Cancer, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hematology, MESH: Pancreas, medicine.disease, Chemotherapy regimen, 3. Good health, Clinical Practice, medicine.anatomical_structure, Diagnosis treatment, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Pancreatic Neoplasms, Pancreas, business, MESH : Combined Modality Therapy, MESH : Pancreatic Neoplasms
Abstract: International audience
Published: 2015

7. Chemotherapy at the End of Life: Factors of Prescription

Author: Julia Salleron, Vincent Massard, Béatrice Weber, Thierry Conroy, Ivan Krakowski, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: Male, MESH: Decision Making, medicine.medical_specialty, MESH: Survival Rate, MESH : Male, medicine.medical_treatment, Decision Making, MESH : Terminal Care, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Humans, Medicine, MESH : Female, MESH: Neoplasms, 030212 general & internal medicine, MESH : Palliative Care, Medical prescription, MESH : France, Intensive care medicine, General Nursing, ComputingMilieux_MISCELLANEOUS, Terminal Care, Chemotherapy, MESH: Humans, business.industry, Palliative Care, MESH : Humans, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, MESH : Survival Rate, MESH : Neoplasms, MESH : Decision Making, MESH: Male, Survival Rate, MESH: France, MESH : Antineoplastic Agents, MESH: Terminal Care, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, MESH: Antineoplastic Agents, Female, MESH: Palliative Care, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, MESH: Female
Abstract: International audience
Published: 2015

8. FLASH-RAS : Etat des lieux des tests RAS chez des patients atteint d’un cancer colorectal métastatique en 2014

Author: Merlin, Jean-Louis, Lièvre, Astrid, Laurent-Puig, Pierre, Ducreux, Michel, Artru, Pascal, Fuchs, Justine, Gicquel, Corinne, Sabourin, Jean-Christophe, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Gustave Roussy (IGR), Hôpital privé Jean Mermoz, Merck Serono, Merck & Co. Inc, CHU Rouen, Normandie Université (NU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and Institut Gustave Roussy ( IGR )
Subjects: [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract: Présentation Poster; National audience
Published: 2015

9. Long-term side effects of radiotherapy for pediatric localized neuroblastoma

Author: Ducassou , Anne, Gambart , Marion, Munzer , Caroline, Padovani , Laetitia, Carrie , Christian, Haas-Kogan , Daphne, Bernier-Chastagner , Valérie, Demoor , Charlotte, Claude , Line, Helfre , Sylvie, Bolle , Stéphanie, Leseur , Julie, Huchet , Aymeri, Rubié , Hervé, Valteau-Couanet , Dominique, Schleiermacher , Gudrun, Coze , Carole, Defachelles , Anne-Sophie, Marabelle , Aurelien, Ducassou , Stéphane, Devalck , Christine, Gandemer , Virginie, Munzer , Martine, Laprie , Anne, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiothérapie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Léon Bérard [Lyon], Dept. of Radiation Oncology, UCSF, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CRLCC Eugène Marquis (CRLCC), CHU Bordeaux [Bordeaux], Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Hématogoie pédiatrique, Institut Jean Godinot [Reims], Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital des Enfants, CHU Toulouse [Toulouse], University of California [San Francisco] (UCSF), University of California-University of California, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Unité d'Hémato-Oncologie, Hôpital des Enfants, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Institut Jean Godinot, CRLCC Jean Godinot, Imagerie cérébrale et handicaps neurologiques, Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpital des enfants, Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), University of California [San Francisco] ( UCSF ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CRLCC Eugène Marquis ( CRLCC ), Institut Gustave Roussy ( IGR ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Université Toulouse III - Paul Sabatier ( UPS ), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: [ SDV ] Life Sciences [q-bio], Radiotherapy, Neoplasien, Late effects, [SDV]Life Sciences [q-bio], Musculoskeletal abnormalities, Skoliose, Strahlentherapie, Radiation therapy, second primary, Scoliosis, Oncology, Spätfolgen, Neoplasms, Muskel-Skelett-Anomalien, zweite primäre, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Introduction - Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. Patients and methods - From 1990-2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. Results - The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5-21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. Conclusion - After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.
Published: 2015

10. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial

Author: Marie-Pierre Galais, Carmen Llacer-Moscardo, Thierry Conroy, Valérie Boige, Jean-Yves Douillard, Beata Juzyna, Eric Francois, Isabelle Martel-Lafay, Olivier Bouché, Gilles Créhange, Jean-Luc Raoul, Antoine Adenis, Laurent Bedenne, Pierre-Luc Etienne, Pierre Michel, Meher Ben Abdelghani, Sophie Gourgou-Bourgade, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Reims (CHU Reims), CRLCC Val d'Aurelle - Paul Lamarque, Institut de Cancérologie de l'Ouest, Clinique Armoricaine de Radiologie [St. Brieuc], Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Hôpital Charles Nicolle [Rouen], Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Paul Strauss, CRLCC Paul Strauss, UNICANCER, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Oscar Lambret - Centre Régional de Lutte contre le Cancer, UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer., Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), CRLCC Eugène Marquis ( CRLCC ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université de Lille-UNICANCER
Subjects: Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, Organoplatinum Compounds, Population, Leucovorin, Gastroenterology, Disease-Free Survival, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Mucositis, Humans, education, Aged, Aged, 80 and over, education.field_of_study, Intention-to-treat analysis, business.industry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Chemoradiotherapy, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, Surgery, Oxaliplatin, Oncology, Fluorouracil, Concomitant, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cisplatin, business, medicine.drug
Abstract: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p0·0001), sensory neuropathy (24 [18%] vs one [1%], p0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group.Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery.UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
Published: 2014

11. Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: Tolerance and efficacy

Author: Christophe Hennequin, Thierry Conroy, Véronique Vendrely, Pierre-Luc Etienne, Jean-François Seitz, Sophie Gourgou-Bourgade, Isabelle Martel-Laffay, Beata Juzyna, Marta Jarlier, Jean-Pierre Gerard, Eric Francois, David Azria, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Service de cancérologie et radiothérapie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Clinique Armoricaine de Radiologie [St. Brieuc], Hôpital Saint-André, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Bordeaux [Bordeaux]-Hôpital Saint -André, Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Oncology, Male, Organoplatinum Compounds, MESH : Retrospective Studies, Colorectal cancer, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, MESH : Aged, Deoxycytidine, 0302 clinical medicine, Elderly, MESH: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Rectal Adenocarcinoma, Medicine, MESH : Neoplasm Staging, MESH : Female, Stage (cooking), Rectal cancer, MESH : Rectal Neoplasms, MESH: Treatment Outcome, MESH: Chemoradiotherapy, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Organoplatinum Compounds, Age Factors, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hematology, Chemoradiotherapy, MESH : Chemoradiotherapy, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, Neoadjuvant Therapy, 3. Good health, Neoadjuvant chemoradiotherapy, Oxaliplatin, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, 030220 oncology & carcinogenesis, MESH : Fluorouracil, 030211 gastroenterology & hepatology, Female, Fluorouracil, medicine.drug, Adult, medicine.medical_specialty, MESH : Male, MESH: Neoadjuvant Therapy, MESH : Treatment Outcome, MESH : Organoplatinum Compounds, MESH : Capecitabine, Capecitabine, 03 medical and health sciences, MESH : Deoxycytidine, Internal medicine, Humans, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, Neoplasm Staging, Retrospective Studies, MESH: Age Factors, Chemotherapy, MESH: Humans, business.industry, Rectal Neoplasms, MESH : Humans, MESH: Deoxycytidine, MESH: Capecitabine, MESH: Rectal Neoplasms, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Comorbidity, MESH: Male, Clinical trial, Exploratory analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, business, MESH : Neoadjuvant Therapy, MESH: Female, MESH: Fluorouracil
Abstract: International audience; BACKGROUND:Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity.PATIENTS AND METHODS:An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemotherapy between the elderly (≥70 years; n=142) and younger patients (
Published: 2014

12. Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: Final results from a randomised phase ii study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan

Author: C. Montoto-Grillot, T. Conroy, E. Francois, J.P. Pignon, J-Y Pierga, E. Boucher, Bruno Chauffert, Antoine Adenis, Michel Ducreux, J.L. Ichante, M. Ychou, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), CRLCC Oscar Lambret, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Eugène Marquis (CRLCC), Centre Régional de Lutte contre le Cancer Val d'Aurelle, Institut Curie, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut Gustave Roussy ( IGR ), Service de biostatistique et d'épidémiologie ( SBE ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Eugène Marquis ( CRLCC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Oncology, MESH: Fatigue, Cancer Research, Time Factors, genetic structures, Colorectal cancer, MESH : Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Phases of clinical research, MESH : Camptothecin, MESH : Diarrhea, MESH : Leucovorin, Gastroenterology, Deoxycytidine, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, Fatigue, MESH: Treatment Outcome, Venous Thrombosis, 0303 health sciences, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH : Venous Thrombosis, 3. Good health, Bevacizumab, MESH : Fatigue, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Diarrhea, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, MESH : Neoplasm Metastasis, FOLFIRI, MESH : Fluorouracil, MESH: Camptothecin, MESH : Disease-Free Survival, MESH : Colorectal Neoplasms, Colorectal Neoplasms, medicine.drug, MESH : Time Factors, Diarrhea, medicine.medical_specialty, Neutropenia, MESH: Neutropenia, MESH : Drug Administration Schedule, MESH : Neutropenia, MESH : Treatment Outcome, MESH: Drug Administration Schedule, Antibodies, Monoclonal, Humanized, Irinotecan, MESH : Capecitabine, Disease-Free Survival, Drug Administration Schedule, MESH : Antibodies, Monoclonal, Humanized, Capecitabine, 03 medical and health sciences, MESH : Deoxycytidine, MESH: Bevacizumab, Internal medicine, medicine, Humans, MESH : Bevacizumab, 030304 developmental biology, XELIRI, MESH: Humans, business.industry, MESH : Humans, MESH: Time Factors, MESH: Deoxycytidine, MESH: Capecitabine, MESH: Quality of Life, MESH : Follow-Up Studies, MESH : Quality of Life, medicine.disease, MESH: Neoplasm Metastasis, eye diseases, digestive system diseases, MESH: Antibodies, Monoclonal, Humanized, MESH: Venous Thrombosis, MESH: Disease-Free Survival, Quality of Life, Camptothecin, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, business, MESH: Leucovorin, MESH: Fluorouracil, MESH: Colorectal Neoplasms, Follow-Up Studies
Abstract: International audience; BACKGROUND:The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC.PATIENTS AND METHODS:Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate.RESULTS:A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively).CONCLUSIONS:This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.
Published: 2013

13. A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Author: Guéant, Jean-Louis, Chéry, Céline, Oussalah, Abderrahim, Nadaf, Javad, Coelho, David, Josse, Thomas, Flayac, Justine, Robert, Aurélie, Koscinski, Isabelle, Gastin, Isabelle, Filhine-Tresarrieu, Pierre, Pupavac, Mihaela, Brebner, Alison, Watkins, David, Pastinen, Tomi, Montpetit, Alexandre, Hariri, Fadi, Tregouët, David, Raby, Benjamin A, Chung, Wendy K., Morange, Pierre-Emmanuel, Froese, D. Sean, Baumgartner, Matthias R., Benoist, Jean-François, Ficicioglu, Can, Marchand, Virginie, Motorin, Yuri, Bonnemains, Chrystèle, Feillet, François, Majewski, Jacek, Rosenblatt, David S., GONNET, JULIE, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), McGill University = Université McGill [Montréal, Canada], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Harvard Medical School [Boston] (HMS), University of Missouri [Columbia] (Mizzou), University of Missouri System, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), University hospital of Zurich [Zurich], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Perelman School of Medicine, University of Pennsylvania, Children’s Hospital of Philadelphia (CHOP ), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), McGill University, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], University of Missouri [Columbia], Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), University of Pennsylvania [Philadelphia], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-15-IDEX-04-LUE,LUE,Lorraine Université d'Excellence(2016), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Mutation, MESH: Metabolism, Inborn Errors, MESH: Pedigree, Science, MESH: Azacitidine, MESH: Peroxiredoxins, MESH: Carrier Proteins, MESH: Base Sequence, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Epistasis, Genetic, lcsh:Science, MESH: Heterozygote, MESH: Humans, MESH: Alleles, nutritional and metabolic diseases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Male, MESH: Vitamin B 12, MESH: Enzyme Inhibitors, MESH: Fibroblasts, MESH: Family Health, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, MESH: Whole Genome Sequencing, MESH: Female
Abstract: To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name “epi-cblC”. The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation. The epimutation is present in three generations and results from PRDX1 mutations that force antisense transcription of MMACHC thereby possibly generating a H3K36me3 mark. The silencing of PRDX1 transcription leads to partial hypomethylation of the epiallele and restores the expression of MMACHC. This example of epi-cblC demonstrates the need to search for compound epigenetic-genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios., Inborn errors of vitamin B12 metabolism of the cblC class are caused by mutations in the MMACHC gene. Here, Guéant et al. report epi-cblC, a class of cblC in which patients are compound heterozygous for a genetic mutation and a secondary epimutation at the MMACHC locus.
Published: 2018

14. Item response models for the longitudinal analysis of health-related quality of life in cancer clinical trials

Author: Barbieri, Antoine, Peyhardi, Jean, Conroy, Thierry, Gourgou, Sophie, Lavergne, Christian, Mollevi, Caroline, IMAG, Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Modeling plant morphogenesis at different scales, from genes to phenotype (VIRTUAL PLANTS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA)-Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Qualité de vie et cancer, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Université Paul-Valéry - Montpellier 3 (UPVM), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Université Paul-Valéry - Montpellier 3 (UM3)
Subjects: FOS: Computer and information sciences, Clinical Trials as Topic, Ordinal categorical data, lcsh:R5-920, Health Status, Health-related quality of life, Longitudinal analysis, Statistics - Applications, Item response theory, humanities, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Neoplasms, Surveys and Questionnaires, Outcome Assessment, Health Care, Linear Models, Quality of Life, Humans, Applications (stat.AP), Longitudinal Studies, Ordinal data, Mixed models, lcsh:Medicine (General), Algorithms, Research Article
Abstract: Background The use of health-related quality of life (HRQoL) as an endpoint in cancer clinical trials is growing rapidly. Hence, research into the statistical approaches used to analyze HRQoL data is of major importance, and could lead to a better understanding of the impact of treatments on the everyday life and care of patients. Amongst the models that are used for the longitudinal analysis of HRQoL, we focused on the mixed models from item response theory, to directly analyze raw data from questionnaires. Methods We reviewed the different item response models for ordinal responses, using a recent classification of generalized linear models for categorical data. Based on methodological and practical arguments, we then proposed a conceptual selection of these models for the longitudinal analysis of HRQoL in cancer clinical trials. Results To complete comparison studies already present in the literature, we performed a simulation study based on random part of the mixed models, so to compare the linear mixed model classically used to the selected item response models. As expected, the sensitivity of the item response models to detect random effects with lower variance is better than that of the linear mixed model. We then used a cumulative item response model to perform a longitudinal analysis of HRQoL data from a cancer clinical trial. Conclusions Adjacent and cumulative item response models seem particularly suitable for HRQoL analysis. In the specific context of cancer clinical trials and the comparison between two groups of HRQoL data over time, the cumulative model seems to be the most suitable, given that it is able to generate a more complete set of results and gives an intuitive illustration of the data. Electronic supplementary material The online version of this article (doi:10.1186/s12874-017-0410-9) contains supplementary material, which is available to authorized users.
Published: 2017

15. Psychological and social determinants of physical activity from diagnosis to remission among French cancer patients (PERTINENCE): protocol for a mixed-method study

Author: Van Hoye, Aurélie, Omorou, Yacobou, Rotonda, Christine, Gendarme, Sophie, Tarquinio, Cyril, Houtmann, Bastien, Peiffert, Didier, Longo, Raffaele, Martin-Krumm, Charles, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), National Clinical Research Platform for Quality of Life in Oncology [Besançon], Centre Pierre Janet [Metz], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'oncologie [Metz], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Religion, Culture et Société, Institut Catholique de Paris (ICP), Institut de Recherche Biomédicale des Armées (IRBA), This project was funded by the French Cancer League: 'Projet de Recherche en Sciences Humaines et Sociales Ligue Contre le Cancer'. The funding is dedicated to project management, data collection and analysis. Intellectual properties belong to the research team., CIC 1433 Epidémiologie clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychologie [Paris], École de Psychologues Praticiens (EPP), Cognitions Humaine et ARTificielle (CHART), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bodescot, Myriam, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Physical activity, Social Determinants of Health, lcsh:Public aspects of medicine, Remission Induction, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RA1-1270, Study Protocol, Mixed method, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Research Design, Neoplasms, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Socio-ecological model, France, Exercise, Qualitative Research, Cancer, Retrospective Studies
Abstract: International audience; BACKGROUND:Many effective physical activity (PA) interventions have focused on individual factors or a single theoretical model, limiting our understanding of the determinants of PA practice and their interactions in the cancer trajectory. The present mixed-method study aims to capture social and psychological determinants of PA practice from diagnosis to remission among cancer patients, and to identify key levers for PA practice.METHODS/DESIGN:A nested sequential mixed-method design QUAN (QUAL+QUAL) will be used, with qualitative studies embedded in the quantitative study to broaden our understanding of the determinants of PA practice. The design is sequential, since qualitative data on medical staff will be collected before patient inclusion (Phase 1), followed by quantitative patient data collection lasting one year (Phase 2) and a final qualitative data collection one year after inclusion (Phase 3). Phase 1 will be a case study in the two hospitals involved in the study, exploring knowledge of and support for PA practice among medical staff. Through interviews and documental analyses, the PA support dynamic will be evaluated with regard to PA prescription. Phase 2 will be a one-year observational study among 693 cancer patients. Quantitative medical, social, dispositional and psychological data, PA practices and preferences, will be collected at diagnosis, and six months and one year thereafter. Phase 3 will be a retrospective study, evaluating societal and policy factors, as well as unexpected factors playing a role in PA levels and preferences among cancer patients. For this phase thirty patients will be identified six months after inclusion on the basis of their PA profiles. Quantitative data will provide the main dataset, whilst qualitative data will complete the picture, enabling determinants of PA practice and their interactions to be captured throughout the cancer trajectory.DISCUSSION:The present study aims to identify key levers and typical trajectories for PA practice among cancer patients, adapted to different times in the course of cancer and taking into account "what works", "for whom", "where" and "how". The challenge is the tailoring of PA interventions to patients at different times in their cancer trajectory, and the implication of medical staff support.TRIAL REGISTRATION:Clinical Trial NCT03919149 , 18 April 2019. Prospectively registered.
Published: 2019

16. Ifosfamide-induced encephalopathy: Brand-name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®)

Author: Jean Vigneron, Benoit Hombourger, Maria Rios, Pauline Lider, Jeremy Chambord, Béatrice Demoré, Catherine Vallance, Fabien Henny, Julia Salleron, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Adult, Male, medicine.medical_specialty, Encephalopathy, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Generic drug, medicine, Drugs, Generic, Humans, Pharmacology (medical), 030212 general & internal medicine, Ifosfamide, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, Brain Diseases, business.industry, Medical record, Incidence (epidemiology), Incidence, Confounding, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Exact test, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, MESH: Ifosfamide-induced encephalopathy, generic, ifosfamide formulation, risk factors, medicine.drug
Abstract: Two forms of ifosfamide are commercially available in France: HOLOXAN® (brand-name drug) and IFOSFAMIDE EG® (generic drug). Following the marketing launch of the generic drug, there has been a significant increase in cases of ifosfamide-induced encephalopathy reported in France. Our objective is to compare the incidence of ifosfamide-induced encephalopathy in adult patients treated with HOLOXAN® or IFOSFAMIDE EG®.This is a retrospective study of adult patients treated with ifosfamide in two medical centers from 2013 to 2017, with data analysed from medical records. Comparisons of patients were made, according to the formulation used and according to the occurrence of ifosfamide-induced encephalopathy. The groups of patients were compared using a chi-square or Fisher's exact test for qualitative parameters and a Wilcoxon test for quantitative parameters. To include confounding factors in the analysis of the impact of drug formulation on the occurrence of ifosfamide-induced encephalopathy, a generalized linear model was performed with the occurrence of ifosfamide-induced encephalopathy as the dependent parameter, and the formulation and the confounding factors as explanatory parameters.A total of 191 patients were included: 103 patients received HOLOXAN® (53.9%) and 88 patients received IFOSFAMIDE EG® (46.1%). In the HOLOXAN® group, the median infusion time was higher (12 hours vs 3h, P 0.001) and aprepitant was administered more frequently (78.6% vs 69.7%, P 0.001) than for the IFOSFAMIDE EG® group. Ifosfamide-induced encephalopathy occurred in 11 patients (5.8%, CI 95% [2.9%, 10.0%]). In the ifosfamide-induced encephalopathy group, median infusion time was higher (12 hours [12; 24] vs 3 hours [2; 12] P 0.001) and a poor performance status was more frequent (54.5% vs 13.9%, P = 0.002) than in the group without ifosfamide-induced encephalopathy. The frequency of ifosfamide-induced encephalopathy in the HOLOXAN® group was 1.9% (2/103) against 10.2% (9/88) in the IFOSFAMIDE EG® group (P = 0.014). Multivariate analysis revealed that treatment with IFOSFAMIDE EG® resulted in significantly more ifosfamide-induced encephalopathies compared to HOLOXAN® (OR and CI 95%:7.4 [1.4; 39.5], P = 0.018). We identified two other risk factors for ifosfamide-induced encephalopathy: long-term infusion and a performance status of two or higher.The formation of chloroethylamine in solution could be the cause of more frequent ifosfamide-induced encephalopathies with IFOSFAMIDE EG® compared to HOLOXAN®. Application of these data could help in the choice of ifosfamide formulation in adult patients to decrease the risk of ifosfamide-induced encephalopathy, and more specifically for patients with risk factors.
Published: 2019

17. The targeting ability of fluorescent quantum dots to the folate receptor rich tumors

Author: Frédéric Marchal, Nicolas Lequeux, Lina Bezdetnaya, Thomas Pons, Tristan Mangeolle, Ilya Yakavets, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Laboratory of Biophysics and Biotechnology [Belarusian], Belarusian State University, Laboratoire de Physique et d'Etude des Matériaux (UMR 8213) (LPEM), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Paris Descartes (LIPADE - EA 2517), Université Paris Descartes - Paris 5 (UPD5), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, This research was funded by the Ligue Nationale Contre le Cancer, the Institut de Cancérologie de Lorraine and the Lorraine Region, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique et d'Etude des Matériaux (LPEM), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Multicellular tumor spheroids, Lung Neoplasms, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030303 biophysics, Biophysics, Photodynamic therapy, Dermatology, In Vitro Techniques, KB Cells, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Folic Acid, In vivo, Cell Line, Tumor, Quantum Dots, Fluorescence microscope, medicine, Humans, Pharmacology (medical), MTT assay, Photodiagnosis, Cytotoxicity, A549 cell, 0303 health sciences, Photosensitizing Agents, Chemistry, Quantum dot, technology, industry, and agriculture, Spheroid, equipment and supplies, 3. Good health, Oncology, Microscopy, Fluorescence, Photochemotherapy, Folate receptor, A549 Cells, Nanoparticles, Mouth Neoplasms, ЕСТЕСТВЕННЫЕ И ТОЧНЫЕ НАУКИ [ЭБ БГУ]
Abstract: International audience; Background: Quantum dots (QDs) bring new insights in cancer theranostics. Exceptional brightness together with the simple possibility to modify surface with targeting molecules make QDs attractive agents in fluorescence guided surgery and photodynamic therapy. Currently, many targeted QDs have been developed for theranostic purpose. However, their targeting ability was tested mainly in two dimensional monolayer tumor cell models, while our study includes 3D tumor model reflecting the specificity of in vivo tumor environment.Methods: Core/multilayer shell CdSe/CdS/ZnS QDs were conjugated with folic acid (FA) and characterized spectroscopically. Cytotoxicity of QDs on KB and A549 cells lines were evaluated using the MTT assay. Cellular uptake of QDs was assessed by epifluorescent microscopy. To study the distribution of QDs in tumor tissue, KB spheroids were prepared by means of the liquid overlay technique and then frozen cut of spheroids treated with QDs were imaged by epifluorescence microscopy.Results: We confirmed the specificity of QD-FA for the folic acid receptor positive KB cells. In 3D tumor spheroid model we demonstrated uptake enhancement of QD-FA compared with non-targeted QD. It was demonstrated that penetration profiles were similar for both QDs with penetration depth never exceeding 100 μm.Conclusions: We have demonstrated the effectiveness of FA conjugated QDs to target tumor spheroids thus confirming the crucial role of FRα receptor as a target. Further improvement of QD-FA targeting ability could be performed using dual targeting different targeting agents, such as FA and cyclic RGD.
Published: 2019

18. Genome-wide profiling of human papillomavirus DNA integration in liquid-based cytology specimens from a Gabonese female population using HPV capture technology

Author: Eric M. Leroy, Nicolas Berthet, Xavier Sastre-Garau, Stéphane Descorps-Declère, Emmanuelle Jeannot, Ismaël Hervé Koumakpayi, Pamela Moussavou-Boundzanga, Ernest Belembaogo, Andriniaina Andy Nkili-Meyong, Ingrid Labouba, Centre International de Recherches Médicales de Franceville, Cancer Institute of Libreville, Département de Biopathologie, Institut Curie, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Cellule d'Intervention Biologique d'Urgence (CIBU), Institut Pasteur [Paris], Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherches Médicales de Franceville (CIRMF), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Genotype, Sequence analysis, Cytodiagnosis, Virus Integration, Population, lcsh:Medicine, Uterine Cervical Neoplasms, Biology, Genome, Article, 03 medical and health sciences, 0302 clinical medicine, Humans, Gabon, lcsh:Science, education, Gene, Papillomaviridae, education.field_of_study, Multidisciplinary, Incidence (epidemiology), Incidence, lcsh:R, Papillomavirus Infections, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Uterine Cervical Dysplasia, Virology, 3. Good health, 030104 developmental biology, Liquid-based cytology, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, lcsh:Q, Female, Ascus, 030217 neurology & neurosurgery
Abstract: Human papillomavirus (HPV) is recognised as the cause of precancerous and cancerous cervical lesions. Furthermore, in high-grade lesions, HPV is frequently integrated in the host cell genome and associated with the partial or complete loss of the E1 and E2 genes, which regulate the activity of viral oncoproteins E6 and E7. In this study, using a double-capture system followed by high-throughput sequencing, we determined the HPV integration status present in liquid-based cervical smears in an urban Gabonese population. The main inclusion criteria were based on cytological grade and the detection of the HPV16 genotype using molecular assays. The rate of HPV integration in the host genome varied with cytological grade: 85.7% (6/7), 71.4% (5/7), 66.7% (2/3) 60% (3/5) and 30.8% (4/13) for carcinomas, HSIL, ASCH, LSIL and ASCUS, respectively. For high cytological grades (carcinomas and HSIL), genotypes HPV16 and 18 represented 92.9% of the samples (13/14). The integrated form of HPV16 genotype was mainly found in high-grade lesions in 71.4% of samples regardless of cytological grade. Minority genotypes (HPV33, 51, 58 and 59) were found in LSIL samples, except HPV59, which was identified in one HSIL sample. Among all the HPV genotypes identified after double capture, 10 genotypes (HPV30, 35, 39, 44, 45, 53, 56, 59, 74 and 82) were detected only in episomal form. Our study revealed that the degree of HPV integration varies with cervical cytological grade. The integration event might be a potential clinical prognostic biomarker for the prediction of the progression of neoplastic lesions.
Published: 2019

19. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

Author: Conroy, Thierry, Hammel, Pascal, Hebbar, Mohamed, Ben Abdelghani, Meher, Wei, Alice, Raoul, Jean-Luc, Choné, Laurence, Francois, Eric, Artru, Pascal, Biagi, James, Lecomte, Thierry, Assenat, Eric, Faroux, Roger, Ychou, Marc, Volet, Julien, Sauvanet, Alain, Breysacher, Gilles, Di Fiore, Frédéric, Cripps, Christine, Kavan, Petr, Texereau, Patrick, Bouhier-Leporrier, Karine, Khemissa-Akouz, Faiza, Legoux, Jean-Louis, Juzyna, Beata, Gourgou, Sophie, O'Callaghan, Christopher, Jouffroy-Zeller, Claire, Rat, Patrick, Malka, David, Castan, Florence, Bachet, Jean-Baptiste, Trials Group, Canadian Cancer, Group, Unicancer-GI–PRODIGE, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, CRLCC Paul Strauss, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital privé Jean Mermoz, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie hepato-pancreato-biliaire, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Louis Pasteur [Colmar] (CH Colmar), CHU Rouen, Normandie Université (NU), CHU Mont de Marsan, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Régional d'Orléans (CHRO), R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Centre Hospitalier Régional d'Orléans (CHR), Service de Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, Leucovorin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Irinotecan, Deoxycytidine, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, Organometallic Compounds, medicine, Adjuvant therapy, Humans, Prospective Studies, Survival rate, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Combination chemotherapy, General Medicine, Middle Aged, medicine.disease, Gemcitabine, 3. Good health, Oxaliplatin, Pancreatic Neoplasms, Drug Combinations, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Folfirinox Regimen, Lung Diseases, Interstitial, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; BACKGROUND:Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.METHODS:We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety.RESULTS:At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P
Published: 2018

20. Recommandations du GEFPICS pour la prise en charge des prélèvements dans le cadre du traitement néoadjuvant du cancer du sein

Author: Maran-Gonzalez, Aurélie, Franchet, Camille, Duprez-Paumier, Raphaelle, Antoine, Martine, Barlier, Catherine, Bécette, Véronique, Berghian, Anca, Blanc-Fournier, Cécile, Brabencova, Eva, Charafe-Jauffret, Emmanuelle, Chenard, Marie-Pierre, Dauplat, Marie-Mélanie, Delrée, Paul, Fleury, Clémence, Garbar, Christian, Ghnassia, Jean-Pierre, Haudebourg, Juliette, MacGrogan, Gaëtan, Mathieu, Marie-Christine, Michenet, Patrick, Penault-Llorca, Frédérique, Poulet, Bruno, Robin, Yves, Roger, Pascal, Russ, Elisabeth, Treilleux, Isabelle, Valent, Alexander, Verriele, Véronique, Vincent-Salomon, Anne, Arnould, Laurent, Lacroix-Triki, Magali, Institut du Cancer de Montpellier (ICM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital René HUGUENIN (Saint-Cloud), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Régional d'Orléans (CHRO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université de Montpellier (UM), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Curie [Paris], Université Lumière - Lyon 2 - UFR de Sciences économiques et de gestion (UL2 UFR SEG), Université Lumière - Lyon 2 (UL2), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Lille Nord de France (COMUE)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CRLCC Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology Bratislava, NUT a RCH, Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'anatomo-pathologie, Centre Jean Perrin, Pathology Department, CRLCC Paul Strauss, Laboratoire d'Anatomo-Pathologie, Hôpital Pasteur [Nice] (CHU), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie, CHU Orléans, CRLCC Jean Perrin, Calculateurs Parallèles (CALCPAR), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-INRIA Rennes, Institut National de Recherche en Informatique et en Automatique (Inria), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Department of Tumor Biology, Institut Curie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Neoplasm, Residual, Tissue sample, Recommandations, [SDV]Life Sciences [q-bio], Biopsy, Prélèvement, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Guidelines, Medical Records, Réponse pathologique, Specimen Handling, Breast cancer, Biomarkers, Tumor, Humans, Néoadjuvant, Breast, Cancer du sein, Microscopy, Sentinel Lymph Node Biopsy, Prognosis, Neoadjuvant Therapy, Tumor Burden, Treatment Outcome, Chemotherapy, Adjuvant, Female, France, Lymph Nodes, Drug Screening Assays, Antitumor, Pathological response
Abstract: International audience; Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).
Published: 2018

21. Oral etoposide in heavily pre-treated metastatic breast cancer: results from the ESME cohort and comparison with other chemotherapy regimens

Author: Jean-Marc Ferrero, Jean-Yves Pierga, Marc Debled, Luc Cabel, Florence Dalenc, Irwin Piot, Bianca Cheaib, Isabelle Desmoulins, Christelle Levy, David Pérol, Anthony Gonçalves, Audrey Mailliez, Marie-Ange Mouret-Reynier, Matthieu Carton, Florence Lerebours, Gaëtane Simon, Claudia Lefeuvre, Jean-Christophe Eymard, Thierry Petit, Marianne Leheurteur, William Jacot, Geneviève Perrocheau, Lionel Uwer, Institut Curie [Saint-Cloud], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Institut Claudius Regaud, CRLCC Oscar Lambret, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), CRLCC Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Institut Jean Godinot, CRLCC Jean Godinot, CRLCC Paul Strauss, CRLCC Jean Perrin, Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Institut Curie - Saint Cloud (ICSC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, medicine.medical_treatment, Administration, Oral, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Oral administration, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Topoisomerase II Inhibitors, skin and connective tissue diseases, Etoposide, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Propensity score matching, Cohort, Oral drug, Female, business, medicine.drug, Follow-Up Studies
Abstract: HER2-negative metastatic breast cancer (MBC) is a common setting in which chemotherapy could be effective even in later lines of treatment. Oral etoposide has demonstrated clinical activity in this setting in small-scale studies, but its efficacy has not been compared to that of other chemotherapy regimens. We used the ESME database (Epidemiological Strategy and Medical Economics), a real-life national French multicentre cohort of MBC patients initiating therapy between 1 January 2008 to 31 December 2014. HER2-negative MBC patients who received oral etoposide as > 3rd chemotherapy line and for more than 14 days were included. Primary objective was progression-free survival (PFS); secondary objectives were overall survival (OS), and propensity-score matched Cox models including comparison with other therapies in the same setting. Three hundred forty-five out of 16,702 patients received oral etoposide and 222 were eligible. Median PFS was 3.2 months [95% CI 2.8–4] and median OS 7.3 months [95% CI 5.7–10.3]. Median PFS did not significantly differ according to the therapeutic line. The only prognostic factor for both PFS and OS was the MBC phenotype (hormone receptor-positive versus triple-negative, HR = 0.71 [95% CI 0.52–0.97], p = 0.028 for PFS and HR = 0.65 [0.46–0.92], p = 0.014 for OS). After matching for the propensity score, no differential effect on PFS or OS was observed between oral etoposide and other chemotherapy regimens administered in the same setting (HR = 0.94 [95% CI 0.77–1.15], p = 0.55 for PFS and HR = 1.10 [95% CI 0.88–1.37], p = 0.40 for OS). Oral etoposide retains some efficacy in selected heavily pre-treated patients with HER2-negative MBC, with the advantages of oral administration.
Published: 2018

22. Pediatric Localized Intracranial Ependymomas: A Multicenter Analysis of the Société Française de lutte contre les Cancers de l'Enfant (SFCE) from 2000 to 2013

Author: Christian Carrie, Christine Kerr, Didier Frappaz, J. Leseur, Claire Alapetite, Aymeri Huchet, Charlotte Demoor-Goldschmidt, Jean-Louis Habrand, Line Claude, Stéphanie Bolle, Elisabeth Le Prisé, Tan Dat Nguyen, Annick Sevely, Xavier Muracciole, Anne Ducassou, Bernard Coche-Dequeant, Léonor Chaltiel, Valérie Bernier-Chastagner, F. Tensaouti, Sergio Boetto, Stéphane Supiot, Anne-Isabelle Bertozzi, Anne Laprie, Laetitia Padovani, Gilles Truc, CRLCC Institut Claudius Regaud, Service de Radiothérapie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Léon Bérard [Lyon], Département d'oncologie en radiothérapie [CHU de la Timone], Assistance Publique - Hôpitaux de Marseille (APHM), Centre Régional de Lutte Contre le Cancer Oscar Lambret, CRLCC René Gauducheau, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), CHU Bordeaux [Bordeaux], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Département de radiothérapie, CRLCC Val d'Aurelle - Paul Lamarque, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Institut Jean Godinot, CRLCC Jean Godinot, Hôpital des Enfants, CHU Toulouse [Toulouse], Département de Neurochirurgie [CHU Toulouse], Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Médical, Institut Claudius Regaud, CHU Marseille, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Jean Godinot [Reims], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Lille-UNICANCER, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Male, Cancer Research, Prognostic factor, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Extent of resection, Disease-Free Survival, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Cumulative incidence, Young adult, Child, ComputingMilieux_MISCELLANEOUS, Chemotherapy, Radiation, business.industry, Brain Neoplasms, Medical record, Infant, Radiotherapy Dosage, Prognosis, Confidence interval, 3. Good health, Oncology, Multicenter study, Ependymoma, 030220 oncology & carcinogenesis, Child, Preschool, Female, business, 030217 neurology & neurosurgery
Abstract: International audience; Purpose - The objective of this study was to analyze survival and prognostic factors for children, adolescents, and young adults treated with postoperative radiation therapy (RT) for intracranial ependymoma. Methods and materials - Between 2000 and 2013, 202 patients aged ≤25 years were treated in the 13 main French pediatric RT reference centers. Their medical records were reviewed for information, treatments received, and survival rates. All children had received postoperative RT- conformal, intensity modulated, or proton beam. In 2009, the prescribed standard dose in France rose from 54 Gy to 59.4 Gy. Results - Median follow-up was 53.8 months (95% confidence interval [CI] 47-63.5). Median age at RT was 5 years (range 1-22), and 32% of the children treated were aged 54 Gy, and 71% received chemotherapy. Of the 84 relapses, 75% were local. The cumulative incidence of local relapse was 24.4% (95% CI 18.2-31.2) at 3 years and 31.3% (95% CI 24-38.9) at 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 50.4% (95% CI 42.2-58) and 71.4% (95% CI 63.1-78.2). Tumor grade was the only prognostic factor for local relapse and DFS. Tumor grade, age, and extent of resection were independent prognostic factors for overall survival. Conclusions - We confirmed several clinical and tumoral prognostic factors in a large French multicenter study. DFS for intracranial ependymoma remains low, and new biological and imaging markers are needed to distinguish among different subtypes, adapt treatments, and improve survival.
Published: 2018

23. RAS mutation testing in patients with metastatic colorectal cancer in French clinical practice: A status report in 2014

Author: Jean-Louis Merlin, Sabine Tong, François Audhuy, Lucie Libert, Roch-Anicet Ossendza, Michel Ducreux, Astrid Lièvre, Corinne Gicquel, Pierre Laurent-Puig, Laurence Moureau-Zabotto, Jean-Christophe Sabourin, Pascal Artru, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hépato-gastro-entérologie [CHU Pontchaillou], CHU Pontchaillou [Rennes], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Régénération et croissance de l'axone = Axonal Growth and Regeneration (NPS-12), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Merck & Co. Inc, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'Hépato-gastro-entérologie [Chalons-en-Champagne], Hôpital de Châlons-en-Champagne, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), This study was sponsored by Merck Santé SAS, Lyon, France, anaffiliate of Merck KGaA, Darmstadt, Germany. The management ofthe study was provided by Merck Santé. The management, monitor-ing, data management and the statistical analyses were performedby, AXONAL-BIOSTATEM, Nanterre, France. The sponsor partici-pated in the design of the study, had oversight on the conduct of thestudy, and participated in interpretation of data and the decisionto publish the results. The corresponding author had full access toall of the data and the final responsibility to submit for publication., Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling ( COSS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Régénération et croissance de l'axone = Axonal Growth and Regeneration ( NPS-12 ), Neuroscience Paris Seine ( NPS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Merck Santé, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Male, 0301 basic medicine, Oncology, Colorectal cancer, DNA Mutational Analysis, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, GTP Phosphohydrolases, Antineoplastic Agents, Immunological, 0302 clinical medicine, Medicine, Molecular Targeted Therapy, Neoplasm Metastasis, Practice Patterns, Physicians', [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, education.field_of_study, medicine.diagnostic_test, Gastroenterology, Antibodies, Monoclonal, Middle Aged, 3. Good health, ErbB Receptors, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Female, France, KRAS, Colorectal Neoplasms, Adult, medicine.medical_specialty, Genotyping, KRAS mutations, Genotype, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Internal medicine, Humans, Genetic Testing, education, Aged, Retrospective Studies, Genetic testing, Hepatology, business.industry, Membrane Proteins, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, digestive system diseases, Genes, ras, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation testing, business, RAS
Abstract: International audience; Background: RAS (NRAS + KRAS) mutation testing is required in addition to simple KRAS testing prior to initiating anti-epidermal-growth-factor-receptor (EGFR) antibodies (MAb) as in metastatic colorectal cancer (mCRC).Aims: To assess prescription and implementation rates of RAS/KRAS mutation testing. To describe the RAS/KRAS mutation test procedure and its impact on therapeutic strategy.Patients and methods: Observational retrospective study conducted from June to September 2014 in all consecutive patients with newly diagnosed mCRC.Results: Data from 375 patients (male: 57.8%; mean age, 65.7 ± 11.7 years) were analysed. RAS/KRAS mutation testing was prescribed in 90.1% of patients (338/375). The test was prescribed within 1 month around mCRC diagnosis and prior to first-line therapy in 73.1% (242/331) and 85.4% (280/328) of patients, respectively. Time from test request to receipt of results was 24.6 ± 17.2 days. 59.7% of patients (190/318) had a mutation, mainly KRAS (47.9%; 152/317). Anti-EGFR MAb was prescribed in 90.9% of RAS-wild-type cases (60/66), consistent with the goal of genotyping-testing in this population.Conclusion: In 2014, RAS genotyping-testing in addition to KRAS testing was routinely prescribed and performed in mCRC patients in France. Time to receive results remains long and must be reduced so as to match clinical practice.
Published: 2018

24. 5-year overall survival after early breast cancer diagnosed during pregnancy: A retrospective case-control multicentre French study

Author: Florence Lerebours, A. Vinceneux, Marc Debled, François Morvan, Thomas Bachelot, Magali Provansal, J-M Ferrero, D. Allouache, Pierre Kerbrat, A. Lesur, L. Vanlemmens, Barbara Pistilli, A Ploquin, E. Tresch, F. Coussy, C Loustalot, Séverine Guiu, Jean-Sebastien Frenel, Roman Rouzier, F. Dalenc, Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CRLCC René Huguenin, Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Léon Bérard [Lyon], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Bergonié [Bordeaux], Centre Eugène Marquis (CRLCC), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier René Dubos [Pontoise], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claudius Regaud, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center Oscar Lambret, CRLCC Oscar Lambret, Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Institut Curie, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Institut Bergonié - CRLCC Bordeaux, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CRLCC Institut Claudius Regaud, Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Pregnancy, Internal medicine, medicine, Overall survival, Humans, 030212 general & internal medicine, Pathological, Neoplasm Staging, Retrospective Studies, Early breast cancer, Chemotherapy, Taxane, business.industry, medicine.disease, Prognosis, 3. Good health, Management, Survival Rate, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, T-stage, Female, France, business, Pregnancy Complications, Neoplastic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Breast cancer diagnosed during pregnancy (BCP) is rare, but the prevalence is expected to rise. Long-term follow-up data regarding this clinically challenging condition are scarce. The main objective of this multicentre case-control French study was to compare the survival between pregnant patients and matched controls. Methods Patients from 27 centres diagnosed between 2000 and 2009 with histologically proven invasive breast cancer occurring during pregnancy were retrospectively included. Controls were matched to BCP patients on age, clinical T stage, hormone receptor, HER2, administration of neo-adjuvant chemotherapy and pathological node involvement in the absence of neo-adjuvant chemotherapy. Five-year overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) rates were estimated using the Kaplan–Meier method. Results One hundred and eleven BCP patients and 253 controls were included. Median age was 33 and 35 years, respectively. Both populations were managed similarly, except for less frequent sentinel node dissection (p = 0.026) and taxane administration (p = 0.03) among BCP patients. Median follow-up was 7.5 years. Survival rates were similar between both BCP and control patients: 5-year OS rates were 83.1% (95% CI: 74.5–89.0) vs 85.5% (95% CI: 80.4–89.4), respectively, p = 0.31; 5-year DFS rates 60.0% (95% CI: 50.1–68.6) vs 68.5% (95% CI: 62.3–73.9), respectively, p = 0.12 and 5-year MFS rates 71.0% (95% CI: 61.3–78.6) and 74.5% (95% CI: 68.6–79.5), respectively, p = 0.21. Conclusion Our study showed that the survival outcomes of patients diagnosed with BCP were not significantly different as compared to those of matched non-pregnant controls. A proper management of women diagnosed with BCP is crucial.
Published: 2018

25. Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort

Author: Laurence Vanlemmens, Marc Debled, Christian Cailliot, Elisa Gobbini, Thomas Bachelot, Monia Ezzalfani, Christelle Jouannaud, Suzette Delaloge, Magali Lacroix-Triki, Anne Patsouris, Thierry Petit, Simone Mathoulin-Pélissier, Veronique Lorgis, William Jacot, Marie Ange Mouret-Reynier, Mathieu Robain, C. Lefeuvre-Plesse, Florence Dalenc, Audrey Lardy Cleaud, Etienne Brain, Christelle Levy, David Pérol, C. Courtinard, Véronique Diéras, Marianne Leheurteur, Lionel Uwer, Anthony Gonçalves, Jean Marc Ferrero, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Curie, Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale supérieure d'architecture de Toulouse (ENSA Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Jean Godinot, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de biologie et pathologie médicales [Gustave Roussy], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Haute Normandie-CRLCC Henri Becquerel, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Center Oscar Lambret, CRLCC Oscar Lambret, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: Adult, Cancer Research, medicine.medical_specialty, Multivariate analysis, Time Factors, Receptor, ErbB-2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Triple Negative Breast Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cancer Survivors, Risk Factors, HER2, Internal medicine, polycyclic compounds, Overall survival, Biomarkers, Tumor, Medicine, Humans, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, Retrospective Studies, Subtypes, Aged, 80 and over, business.industry, Time trends, Hazard ratio, Middle Aged, Metastatic breast cancer, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Cohort, Observational study, Female, France, business, Receptors, Progesterone
Abstract: Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort.ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts.Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes.
Published: 2018

26. A Model of Chronic Exposure to Unpredictable Mild Socio-Environmental Stressors Replicates Some Spaceflight-Induced Immunological Changes

Author: Julianne Mathiot, Emilien Stragier, Laurence Lanfumey, Jean-Louis Merlin, Charles Cohen-Salmon, Jean-Pol Frippiat, Christine Legrand-Frossi, Fanny Gaignier, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Toxicologie et biométrologie (TB), Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Vulnérabilité Adaptation et Psychopathologie (VAP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: 0301 basic medicine, Chronic exposure, lymphocytes, Physiology, mouse model, Splenic lymphocyte, Serum iga, Spaceflight, lcsh:Physiology, law.invention, spaceflight, 03 medical and health sciences, stress, Immune system, law, Immunity, Physiology (medical), Medicine, antibodies, Original Research, lcsh:QP1-981, business.industry, Stressor, cytokines, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Socio environmental, Immunology, business
Abstract: International audience; During spaceflight, astronauts face radiations, mechanical, and socio-environmental stressors. To determine the impact of chronic socio-environmental stressors on immunity, we exposed adult male mice to chronic unpredictable mild psychosocial and environmental stressors (CUMS model) for 3 weeks. This duration was chosen to simulate a long flight at the human scale. Our data show that this combination of stressors induces an increase of serum IgA, a reduction of normalized splenic mass and tends to reduce the production of pro-inflammatory cytokines, as previously reported during or after space missions. However, CUMS did not modify major splenic lymphocyte sub-populations and the proliferative responses of splenocytes suggesting that these changes could be due to other factors such as gravity changes. Thus, CUMS, which is an easy to implement model, could contribute to deepen our understanding of some spaceflight-associated immune alterations and could be useful to test countermeasures.
Published: 2018

27. Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study

Author: Brice, Malgras, Etienne, Gayat, Olivier, Aoun, Réa, Lo Dico, Clarisse, Eveno, Karine, Pautrat, Jean-Baptiste, Delhorme, Guillaume, Passot, Frédéric, Marchal, Olivia, Sgarbura, Gwenael, Ferron, Diane, Goéré, Thierry, Andre, Marc, Pocard, Franck, Zinzindohoue, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Hôpital d'Instruction des Armées Bégin [Saint-Mandé, France], Université Paris Diderot - Paris 7 (UPD7), Hôpital d'instruction des armées Bégin, Hôpital d'Instruction des Armées Bégin, Department of Gastroenterological Surgery, Département de chirurgie générale et digestive [CHU Strasbourg], Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Département de chirurgie viscérale [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Oncology, Male, Mesothelioma, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], Mitomycin, Irinotecan, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Prospective Studies, 10. No inequality, Survival rate, Peritoneal Neoplasms, Performance status, business.industry, Mesothelioma, Malignant, Combination chemotherapy, Hyperthermia, Induced, Middle Aged, medicine.disease, Prognosis, Combined Modality Therapy, 3. Good health, Oxaliplatin, Survival Rate, Regimen, Doxorubicin, 030220 oncology & carcinogenesis, Chemotherapy, Cancer, Regional Perfusion, Peritoneal mesothelioma, 030211 gastroenterology & hepatology, Surgery, Hyperthermic intraperitoneal chemotherapy, Female, Cisplatin, business, Erythrocyte Transfusion, medicine.drug, Follow-Up Studies
Abstract: International audience; Background: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM).Objective: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM.Methods: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases.Results: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype.Conclusions: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.
Published: 2018

28. Prospective Assessment of First-Year Quality of Life After Pelvic Exenteration for Gynecologic Malignancy: A French Multicentric Study

Author: G. Ferron, P. Morice, Frédéric Marchal, I. Jaffré, Michel Rivoire, Eric Lambaudie, G. Houvenaeghel, Denis Querleu, Eberhard Stoeckle, F. Foucher, Pierre Meeus, Sebastien Gouy, Thomas Filleron, J-M Classe, Pierre-Emmanuel Colombo, N. Chopin, Vincent Lavoué, Fabrice Narducci, Jean Levêque, Eva Jouve, Philippe Rouanet, Frédéric Guyon, Alejandra Martinez, J. L. Verheaghe, Eric Leblanc, A. Mourregot, Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Département de chirurgie gynécologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, CRLCC Institut Claudius Regaud, Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Oscar Lambret, Institut Bergonié - CRLCC Bordeaux, and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: medicine.medical_treatment, 0302 clinical medicine, MESH: Pelvic Exenteration, MESH: Genital Neoplasms, Female, Quality of life, Surgical oncology, MESH: Postoperative Period, Surveys and Questionnaires, Medicine, Postoperative Period, Prospective Studies, Prospective cohort study, MESH: Aged, 030219 obstetrics & reproductive medicine, MESH: Middle Aged, MESH: Follow-Up Studies, Middle Aged, Prognosis, humanities, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Female, medicine.symptom, Psychosocial, Adult, medicine.medical_specialty, Genital Neoplasms, Female, [SDV.CAN]Life Sciences [q-bio]/Cancer, Anorexia, MESH: Prognosis, 03 medical and health sciences, Body Image, Humans, MESH: Surveys and Questionnaires, MESH: Body Image, Aged, MESH: Humans, Pelvic exenteration, business.industry, General surgery, MESH: Quality of Life, MESH: Adult, MESH: Prospective Studies, Pelvic Exenteration, Surgery, Gynecologic malignancy, Quality of Life, Sexual function, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BACKGROUND:Pelvic exenteration remains one of the most mutilating procedures, with important postoperative morbidity, an altered body image, and long-term physical and psychosocial concerns. This study aimed to assess quality of life (QOL) during the first year after pelvic exenteration for gynecologic malignancy performed with curative intent.METHODS:A French multicentric prospective study was performed by including patients who underwent pelvic exenteration. Quality of life by measurement of functional and symptom scales was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires before surgery, at baseline, and 1, 3, 6, and 12 months after the procedure.RESULTS:The study enrolled 97 patients. Quality of life including physical, personal, fatigue, and anorexia reported in the QLQ-C30 was significantly reduced 1 month postoperatively and improved at least to baseline level 1 year after the procedure. Body image also was significantly reduced 1 month postoperatively. Global health, emotional, dyspnea, and anorexia items were significantly improved 1 year after surgery compared with baseline values. Unlike younger patients, elderly patients did not regain physical and social activities after pelvic exenteration.CONCLUSIONS:Therapeutic decision on performing a pelvic exenteration can have a severe and permanent impact on all aspects of patients' QOL. Deterioration of QOL was most significant during the first 3 months after surgery. Elderly patients were the only group of patients with permanent decreased physical and social function. Preoperative evaluation and postoperative follow-up evaluation should include health-related QOL instruments, counseling by a multidisciplinary team to cover all aspects concerning stoma care, sexual function, and long-term concerns after surgery.
Published: 2018

29. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma

Author: Christian Beisland, Jean-Christophe Bernhard, B. Laguerre, Stéphane Oudard, Marine Gross-Goupil, Alain Ravaud, Arnaud Mejean, Marc-Olivier Timsit, Lionnel Geoffrois, Claude Linassier, Frederic Rolland, Luc Cormier, Laurent Guy, Karim Bensalah, Jacques Hubert, Sandra Colas, Christine Theodore, Eric Lechevallier, Laurence Albiges, Simon Thezenas, Jean-Baptiste Beauval, Bernard Escudier, Thierry Lebret, Michael Aitchison, Jean-Jacques Patard, Herve Lang, Antoine Thiery-Vuillemin, Christine Chevreau, G. Gravis, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Saint-André, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, URC, hôpital Necker Enfants Maladies, Paris, CHU Pontchaillou [Rennes], Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Urologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Solvay Silica, Solvay (France), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), CHU Marseille, Hôpital Foch [Suresnes], Institut Claudius Regaud, Service de radiothérapie, CRLCC Eugène Marquis (CRLCC), Université libre de Bruxelles (ULB), Comité de Cancérologie (CCAFU), Association Française d'Urologie, Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Développement et amélioration des plantes (UMR DAP), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), CRLCC Institut Claudius Regaud, Université Libre de Bruxelles [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Indoles, Randomization, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Antineoplastic Agents, urologic and male genital diseases, Nephrectomy, Risk Assessment, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, law, Renal cell carcinoma, Sunitinib, medicine, Carcinoma, Humans, Pyrroles, Carcinoma, Renal Cell, Aged, Neoplasm Staging, Aged, 80 and over, business.industry, Patient Selection, Cancer, General Medicine, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Survival Analysis, Kidney Neoplasms, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Female, business, Follow-Up Studies, medicine.drug
Abstract: International audience; BACKGROUND Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS In this phase 3 trial, we randomly assigned, in a 1: 1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority
Published: 2018

30. mTHPC-loaded extracellular vesicles outperform liposomal and free mTHPC formulations by an increased stability, drug delivery efficiency and cytotoxic effect in tridimensional model of tumors

Author: Lina Bezdetnaya, Florence Gazeau, Jordane Jasniewski, Henri-Pierre Lassalle, Max Piffoux, Jean-Michel Guigner, Amanda Brun, Marie Millard, Ilya Yakavets, Claire Wilhelm, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Belarusian State University, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Biomolécules (LIBio), Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Matière et Systèmes Complexes (MSC)
Subjects: medicine.medical_treatment, Pharmaceutical Science, Photodynamic therapy, Antineoplastic Agents, Apoptosis, 02 engineering and technology, In Vitro Techniques, 010402 general chemistry, 01 natural sciences, Extracellular vesicles, multicellular tumor spheroid, Drug Stability, Spheroids, Cellular, polycyclic compounds, medicine, Human Umbilical Vein Endothelial Cells, Tumor Cells, Cultured, Cytotoxic T cell, Humans, heterocyclic compounds, Liposome, Drug Carriers, Microscopy, Confocal, nanocarriers, Chemistry, organic chemicals, lcsh:RM1-950, General Medicine, 021001 nanoscience & nanotechnology, 0104 chemical sciences, lcsh:Therapeutics. Pharmacology, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Mesoporphyrins, Photochemotherapy, photodynamic therapy, Drug delivery, Liposomes, Biophysics, Nanoparticles, Nanocarriers, 0210 nano-technology, extracellular vesicles, HT29 Cells, mTHPC, Research Article
Abstract: Efficient photodynamic therapy with meta-tetra(hydroxyphenyl)chlorine requires the application of specific nanoformulations. mTHPC liposomal formulation (Foslip®) demonstrated favorable pharmacokinetics properties. However, rapid liposomes destruction in circulation and rapid mTHPC release impedes Foslip® applications. Alternatively, mTHPC nanovectorization using extracellular vesicles (EVs) could be an attractive option. EVs are naturally secreted by the organism to play a role in intercellular communication due to the capacity to transport proteins and nucleic acids. EVs also possess a natural ability to deliver therapeutic molecules into cancer cells. The aim of the present study was to evaluate photophysical and photobiological properties of mTHPC loaded in endothelial EVs as nanocarriers. We also studied efficiency of nanovectorisation on mTHPC distribution and PDT activity in multicellular tumor spheroids (MCTSs). MCTS is a nonvascularized in vitro 3D model of cells that mimics a similar microenvironment to in vivo situation. mTHPC-EVs were characterized by means of spectroscopic techniques, flow cytometry and nanoparticle tracking analysis. Compared with Foslip®, mTHPC-EVs are stable in murine plasma. Better mTHPC accumulation and penetration (up to 100 µm) in MCTS was observed for mTHPC-EVs compared with liposomal mTHPC. These factors could explain enhanced photodynamic activity of mTHPC-EVs compared with free and liposomal mTHPC. The light dose inducing 50% of cell death with mTHPC-EVs was 4 and 2.5-times lower than that of free and liposomal mTHPC. The obtained results demonstrate that EVs should be considered as perspective nanocarriers for mTHPC-mediated PDT.
Published: 2018

31. Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study

Author: Gilles Créhange, François Ghiringhelli, A. Leroux, Aurélie Bertaut, F. Arbez-Gindre, Céline Mirjolet, Sylvain Ladoire, J. F. Bosset, Christophe Borg, Céline Charon-Barra, Didier Peiffert, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de Pathologie [CHU Besançon], Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz [Besançon], Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC )
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Oncology, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, lcsh:RC254-282, radiation therapy, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Immunology and Allergy, rectal cancer, translational study, Original Research, Univariate analysis, business.industry, Tumor-infiltrating lymphocytes, Dose fractionation, FOXP3, hemic and immune systems, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, tumor-infiltrating lymphocytes, lcsh:RC581-607, business, Adjuvant
Abstract: IF 7.719; International audience; Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p
Published: 2017

32. Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers

Author: Géraldine Perkins, Alexandre Harlé, Pierre Laurent-Puig, Hélène Blons, Camilla Pilati, Julia Salleron, Jean-Louis Merlin, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL) - Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Oncology, Cancer Research, Colorectal cancer, MAP Kinase Kinase 1, pEGFR, Prostate cancer, FOLFOX, cetuximab, Phosphorylation, Aged, 80 and over, metastatic colorectal cancer, Antibodies, Monoclonal, Middle Aged, 3. Good health, ErbB Receptors, FOLFIRI, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Colorectal Neoplasms, Liver cancer, Signal Transduction, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, MAP Kinase Signaling System, medicine.drug_class, EGFR, pAKT, Monoclonal antibody, Disease-Free Survival, Young Adult, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Biomarkers, Tumor, medicine, Humans, Lung cancer, Molecular Diagnostics, Aged, Oncogene, business.industry, AKT, medicine.disease, ras Proteins, panitumumab, business, Proto-Oncogene Proteins c-akt, phosphoproteins, RAS
Abstract: International audience; Background:RAS wild-type (RASw/t) tumours have been associated with better outcomes in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal antibodies (mAb). We investigated the expression of EGFR downstream proteins under their active phosphorylated forms as potential markers in response to these patients.Methods:One-hundred tumour samples were collected from patients with mCRC refractory to FOLFOX and/or FOLFIRI and treated by a combination of chemotherapy with anti-EGFR mAb. The outcomes were measured on response evaluation criteria in solid tumour (RECIST), progression-free survival (PFS) and overall survival (OS). All samples were assessed for RAS and BRAF mutations, and the key phosphorylated proteins of EGFR downstream signalling were quantitatively analysed using the BioPlex Protein array.Results:Among the 60 RASw/t patients, 45.0% achieved a complete or partial response when treated with anti-EGFR mAb. Expression of pAKT, pERK1/2 and pMEK1 was significantly lower in RASw/t patients (P=0.0246; P=0.004; P=0.0110, respectively). The response rate was significantly higher for RASw/t patients who express pEGFR and pAKT (P=0.0258; P=0.0277, respectively).Conclusions:Overexpression of pEGFR and pAKT may predict the response rate in RASw/t patients treated with anti-EGFR mAb. On the basis of our results, we hypothesise that the association of anti-EGFR mAb and anti-AKT therapies could be of interest.
Published: 2015

33. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial

Author: Nadine Houede, Claude Linassier, Philippe Beuzeboc, Paule Chinet-Charrot, Laura Faivre, Loic Mourey, Aude Flechon, Frank Priou, Gael Deplanque, Jean-Marc Ferrero, Jean-Louis Davin, Christine Theodore, Muriel Habibian, Brigitte Laguerre, Remy Delva, Anne-Laure Martin, Ivan Krakowski, Agnès Laplanche, Karim Fizazi, Frederic Rolland, Jean-Luc Labourey, Stéphane Culine, Jean-François Berdah, Gwenaelle Gravis, François Lesaunier, Isabelle Cojean-Zelek, Eric Legouffe, Alain Ravaud, Marjorie Baciuchka, Stéphane Oudard, Jean-Léon Lagrange, Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Hôpital Foch [Suresnes], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Hôpital privé Toulon Hyères : Sainte Marguerite, Hôpital de la Timone [CHU - APHM] (TIMONE), CRLCC Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Hôpital Saint-André, Groupe Hospitalier Diaconesses Croix Saint-Simon, Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Limoges, CRLCC Henri Becquerel, ONCOGARD - NIMES, Institut de Cancérologie du GARD (Instit Cancéro - GARD), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Saint-Joseph, Institut Curie, Institut Sainte Catherine [Avignon], UNICANCER [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Curie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université Côte d'Azur (UCA)-UNICANCER, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
Subjects: Male, medicine.medical_specialty, Maximum Tolerated Dose, Population, 030232 urology & nephrology, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Docetaxel, Kaplan-Meier Estimate, Disease-Free Survival, Drug Administration Schedule, Androgen deprivation therapy, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Invasiveness, education, Aged, Neoplasm Staging, Proportional Hazards Models, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Standard treatment, Goserelin, Prostatic Neoplasms, Cancer, Androgen Antagonists, Middle Aged, Prostate-Specific Antigen, medicine.disease, Survival Analysis, 3. Good health, Surgery, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Estramustine, Taxoids, France, Neoplasm Recurrence, Local, business, Follow-Up Studies, medicine.drug
Abstract: International audience; BACKGROUND:Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer.METHODS:We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2) and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731.FINDINGS:We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1-9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54-0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths.INTERPRETATION:Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival.FUNDING:Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.
Published: 2015

34. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

Author: Manfred B. Lutz, Roberto Labianca, Patrick Pessaux, Bert A. Bonsing, Benoist Chibaudel, David Malka, Claudio Bassi, Sophie Gourgou-Bourgade, Geertjan van Tienhoven, Pascal Hammel, Carine Bellera, Laeticia Dahan, Jean-Luc Van Laethem, Daniela Aust, Emmanuel Chamorey, Jean Robert Delpero, Josep Tabernero, Adelaide Dousseau, Teresa Macarulla, Franck Bonnetain, Julien Taieb, Karin Haustermans, Laurence Collette, Thomas Aparicio, François Lacaine, John P. Neoptolemos, Simone Mathoulin-Pélissier, Bengt Glimelius, Thierry Conroy, Paula Ghaneh, Alain Sauvanet, Erich Gerber, Christos Dervenis, Aurélien Latouche, Murielle Mauer, Michel Ducreux, Valérie Jooste, Virginie Berger, Jocelyn Gal, Alain Hendlisz, Aimery de Gramont, Emmanuel Mitry, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), UNICANCER, Leiden University Medical Center (LUMC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Université Victor Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Uppsala Universitet [Uppsala], University Hospitals Leuven [Leuven], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), G.B. Rossi Hospital, Verona University, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cooperator Multidisciplinary Oncology Group (GERCOR), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Agia Olga Hospital [Athènes] (Konstantopoulio ), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut für Radioonkologie, Royal Liverpool University Hospital, University of Liverpool-Royal Liverpool and Broadgreen University Hospital NHS Trust, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut Jules Bordet [Bruxelles], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Azienda Ospedaleria Ospedali Riuniti di Bergamo, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CaritasKlinikum Saarbrücken, Vall d'Hebron University Hospital [Barcelona], European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Curie [Paris], CRLCC René Huguenin, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service d’Hépatologie [Hôpital Beaujon], Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Academisch Medisch Centrum bij, Universiteit van Amsterdam (UvA), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU Tenon [APHP], Hôpital Erasme (Bruxelles), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Carl Gustav Carus University ( DRESDEN - CGCU ), Technische Universität Dresden ( TUD ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Antoine Lacassagne, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group ( GERCOR ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut Paoli Calmettes, Agia Olga Hospital [Athènes] ( Konstantopoulio ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Beaujon, Institut Jules Bordet, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), European Organisation for Research and Treatment of Cancer [Bruxelles] ( EORTC ), European Cancer Organisation [Bruxelles] ( ECCO ), Institut Curie, L'Institut hospitalo-universitaire de Strasbourg ( IHU Strasbourg ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Universiteit van Amsterdam ( UvA ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Bergonié - CRLCC Bordeaux, Universiteit Leiden, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Verona = University of Verona (UNIVR), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Oncology, Cancer Research, Pathology, Delphi Technique, MESH : Randomized Controlled Trials as Topic, MESH: Delphi Technique, MESH : Consensus, law.invention, Clinical trials, 0302 clinical medicine, Pancreatic cancer, Time to event end-point, Consensus, Guidelines, Methodology, Clinical trials, Randomized controlled trial, law, 030212 general & internal medicine, Time to event end-point, Randomized Controlled Trials as Topic, Event (probability theory), MESH: Endpoint Determination, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 16. Peace & justice, 3. Good health, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, MESH : Endpoint Determination, MESH: Pancreatic Neoplasms, medicine.medical_specialty, Consensus, Endpoint Determination, Guidelines, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Pancreatic cancer, medicine, Overall survival, Humans, MESH: Consensus, Distributed File System, neoplasms, MESH: Humans, End point, business.industry, MESH : Humans, Methodology, Cancer, medicine.disease, Pancreatic Neoplasms, Clinical trial, MESH: Randomized Controlled Trials as Topic, MESH : Delphi Technique, MESH: Disease-Free Survival, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Pancreatic Neoplasms
Abstract: International audience; BACKGROUND:Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.METHODS:Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).RESULTS:For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.CONCLUSION:The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
Published: 2014

35. Radiation plus docetaxel and cisplatin in locally advanced pancreatic carcinoma: A non-comparative randomized phase II trial

Author: Frédéric Viret, Carmen Llacer, Marc Giovannini, Antoine Adenis, Thierry Conroy, Valérie Boige, Didier Peiffert, Michel Ducreux, Moncef Abbas, Beata Juzyna, Charlotte Baey, Jean-Pierre Pignon, Françoise Mornex, Patrice Cellier, Jaafar Bennouna, Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CRLCC Val d'Aurelle - Paul Lamarque, CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Department of Radiation Oncology, Centre Hospitalier Universitaire Lyon Sud, Pierre Benite, France, Hospices Civils de Lyon (HCL), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Centre Oscar Lambret [Lille], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Male, Oncology, medicine.medical_treatment, MESH: Taxoids, Phases of clinical research, Docetaxel, Gastroenterology, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, 030212 general & internal medicine, MESH: Chemoradiotherapy, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Chemoradiotherapy, Middle Aged, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, MESH: Young Adult, MESH: Survival Analysis, 030220 oncology & carcinogenesis, Female, Taxoids, Fluorouracil, MESH: Pancreatic Neoplasms, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Antineoplastic Agents, Radio-chemotherapy, MESH: Drug Administration Schedule, Drug Administration Schedule, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, MESH: Adolescent, Cisplatin, MESH: Humans, Hepatology, business.industry, MESH: Adult, Survival Analysis, MESH: Male, Confidence interval, Pancreatic Neoplasms, Radiation therapy, Regimen, MESH: Cisplatin, MESH: Antineoplastic Agents, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pancreatic carcinoma, business, MESH: Female, MESH: Fluorouracil
Abstract: Background We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported. Methods Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20 mg/m2 and cisplatin 20 mg/m2/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54 Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate. Results 51 patients from 7 centres were included in the docetaxel–cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26–53). Median overall survival was 9.6 months (95% confidence interval: 2.4–60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%). Conclusions Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity.
Published: 2014

36. Predictive factors for early progression during induction chemotherapy (IC) and chemotherapy-free interval (CFI): Analysis from PRODIGE 9 trial

Author: E. Francois, Oana Cojocarasu, Joëlle Egreteau, Côme Lepage, Julien Taieb, K. Le Malicot, Thomas Aparicio, Veronique Guerin-Meyer, François Ghiringhelli, O. Bouche, Jaafar Bennouna, J-B. Bachet, Laetitia Dahan, M-C. Kaminsky-Forrett, Christian Borel, J.M. Phelip, Roger Faroux, Mohamed Gasmi, J.-M. Gornet, Valérie Boige, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss de Lutte contre le Cancer (Strasbourg), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oncologie medicale (CH Bretagne Sud, Lorient), CH Bretagne Sud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémato-oncologie (CH du Mans), Centre Hospitalier du Mans, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service d'Oncologie Médicale [Angers], Centre Paul Papin, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne de Nice, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Aix Marseille Université ( AMU ) -Hôpital Saint-Joseph [Marseille], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Oncology, 0303 health sciences, Chemotherapy, medicine.medical_specialty, business.industry, medicine.medical_treatment, Induction chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, 3. Good health, Free interval, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Predictor variable, business, 030304 developmental biology
Abstract: IF 11.855; International audience
Published: 2017

37. Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment

Author: S. El Messaoudi, Romain Meddeb, Eric Assenat, Rosine Guimbaud, Céline Gavoille, Pascal Artru, B. Auzemery, Jean-Luc Raoul, Muriel Mathonnet, Christophe Borg, Denis Pezet, O. Bouche, Catherine Fiess, Caroline Mollevi, C. de la Fouchardiere, A.R. Thierry, Evelyne Lopez-Crapez, Brice Pastor, M. Ychou, Cynthia Sanchez, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Toulouse [Toulouse], Service Chirurgie Digestive, CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CRLCC Val d'Aurelle - Paul Lamarque, Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Oncology, Neuroblastoma RAS viral oncogene homolog, Adult, Male, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Colorectal cancer, Concordance, Population, Antineoplastic Agents, Bioinformatics, medicine.disease_cause, Genetic analysis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Biopsy, medicine, Humans, Point Mutation, Prospective Studies, Neoplasm Metastasis, education, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, DNA, Neoplasm, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, ErbB Receptors, 030104 developmental biology, Genes, ras, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Personalized medicine, KRAS, business, Colorectal Neoplasms
Abstract: Background While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. Results Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. Conclusion Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
Published: 2017

38. New advances in DPYD genotype and risk of severe toxicity under capecitabine

Author: Jean-Louis Merlin, Frédéric Pinguet, Fabienne Thomas, N. Dohollou, Alexandre Evrard, Philippe Follana, Mireille Mousseau, Emmanuel Chamorey, Christophe Ferrand, Gérard Milano, Marie-Christine Etienne-Grimaldi, Gilles Romieu, André B.P. van Kuilenburg, Laurence Llorca, Rémy Largillier, V. Servent, Thomas Bachelot, Judith L Meijer, Litaty Mbatchi, David Salgado, Jean-Christophe Boyer, Jean-Pierre Desvignes, Véronique Diéras, Jacques Bonneterre, Yann Château, Christine Bobin-Dubigeon, Christophe Béroud, Etienne Chatelut, Henri Roché, Anthony Gonçalves, Loic Chaigneau, Jean-Marc Ferrero, Xavier Pivot, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Claudius Regaud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Val d'Aurelle - Paul Lamarque, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Curie [Paris], Centre Azureen de cancérologie, Service d'oncologie médicale, CHU Grenoble-Hôpital Michallon, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'oncologie médicale, Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER, Polyclinique Bordeaux Nord Aquitaine, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Institut Claudius Regaud, Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Val d'Aurelle-Paul Lamarque, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre Léon Bérard [Lyon], Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Institut Curie, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université ( AMU ), CRLCC Oscar Lambret, Center Oscar Lambret, Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Université de Lille-UNICANCER, Polyclinique Bordeaux Nord Aquitaine (PBNA), AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA - Cancer biology and immunology, Laboratory Genetic Metabolic Diseases, CCA -Cancer Center Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Salgado, David
Subjects: Oncology, lcsh:Medicine, Toxicology, Pathology and Laboratory Medicine, 030226 pharmacology & pharmacy, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Predictive toxicology, Genotype, Medicine and Health Sciences, Prospective Studies, Prospective cohort study, lcsh:Science, Exome, Multidisciplinary, Nucleotides, Genomics, Middle Aged, 3. Good health, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer treatment, Female, medicine.drug, Research Article, Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Genotyping, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Genome Complexity, Research and Analysis Methods, Polymorphism, Single Nucleotide, Capecitabine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Dihydropyrimidine dehydrogenase, Genetics, Humans, Uracils, Molecular Biology Techniques, Molecular Biology, Dihydrouracil Dehydrogenase (NADP), Alleles, Aged, Nucleobases, Toxicity, business.industry, lcsh:R, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biology and Life Sciences, Computational Biology, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, DPYD, lcsh:Q, business, Biomarkers
Abstract: International audience; Background: Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants and toxicity in advanced breast cancer patients receiving capecitabine.Methods: Two-hundred forty-three patients were analysed (88.5% capecitabine monotherapy). Grade 3 and grade 4 capecitabine-related digestive and/or neurologic and/or hemato-toxicities were observed in 10.3% and 2.1% of patients, respectively. DPYD exome, along with flanking intronic regions 3’UTR and 5’UTR, were sequenced on MiSeq Illumina. DPD phenotype was assessed by pre-treatment plasma uracil (U) and dihydrouracil (UH2) measurement.Results: Among the 48 SNPs identified, 19 were located in coding regions, including 3 novel variations, each observed in a single patient (among which, F100L and A26T, both pathogenic in silico). Combined analysis of deleterious variants *2A, I560S (*13) and D949V showed significant association with grade 3–4 toxicity (sensitivity 16.7%, positive predictive value (PPV) 71.4%, relative risk (RR) 6.7, p16 ng/ml) did not substantially increase the sensitivity, while impairing PPV and RR.Conclusions: Exploring an extended set of deleterious DPYD variants improves the performance of DPYD genotyping for predicting both grade 3–4 and grade 4 toxicities (digestive and/or neurologic and/or hematotoxicities) related to capecitabine, as compared to conventional genotyping restricted to consensual variants *2A, *13 and D949V.
Published: 2017

39. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial

Author: Lionnel Geoffrois, Remy Delva, N. Houede, Frederic Rolland, Agnès Laplanche, J.-C. Eymard, B. Laguerre, Aude Flechon, Karim Fizazi, Stéphane Culine, D. Burcoveanu, G. Gravis, Christine Chevreau, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, CRLCC Eugène Marquis (CRLCC), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), CRLCC Jean Godinot, CRLCC René Gauducheau, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut Bergonié - CRLCC Bordeaux, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Bergonié [Bordeaux], Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Oncology, 030232 urology & nephrology, Salvage therapy, Kaplan-Meier Estimate, Deoxycytidine, Gastroenterology, Testicular Neoplasms/*drug therapy/mortality/pathology, 0302 clinical medicine, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Ifosfamide, Hematology, Middle Aged, Neoplasms, Germ Cell and Embryonal, Ifosfamide/administration & dosage, Chemotherapy regimen, 3. Good health, Treatment Outcome, Germ Cell and Embryonal/*drug therapy/mortality/secondary, Lymphatic Metastasis, 030220 oncology & carcinogenesis, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Drug Administration Schedule, Young Adult, 03 medical and health sciences, Testicular Neoplasms, Internal medicine, Deoxycytidine/administration & dosage/analogs & derivatives, medicine, Local/*drug therapy, Humans, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Progression-free survival, Survival rate, Salvage Therapy, business.industry, medicine.disease, Gemcitabine, Regimen, Neoplasm Recurrence, Cisplatin, Neoplasm Recurrence, Local, business, Cisplatin/administration & dosage, Febrile neutropenia
Abstract: International audience; BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate \textless50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 mug/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.
Published: 2014

40. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial

Author: Pierre Laurent-Puig, Sylvain Poujol, Françoise Desseigne, S. Thezenas, Thibault Mazard, Evelyne Crapez, Emmanuelle Samalin, E. Francois, Antoine Adenis, T. Conroy, J.F. Seitz, Julien Taieb, M.P. Galais, Jaafar Bennouna, F. Boissière, Marc Ychou, Eric Assenat, O. Bouche, Frédéric Bibeau, CRLCC Val d'Aurelle - Paul Lamarque, Hôpital universitaire Robert Debré [Reims], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLC Val d'Aurelle-Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Oscar Lambret, Institut de Cancérologie de l'Ouest, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, Cancer Research, Colorectal cancer, medicine.medical_treatment, Camptothecin/administration & dosage/analogs & derivatives, Gastroenterology, tyrosine kinase inhibitor, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, 80 and over, clinic, Aged, 80 and over, education.field_of_study, metastatic colorectal cancer, ras Proteins/*genetics, Mutation, Middle Aged, Sorafenib, 3. Good health, Oncology, Disease Progression, Female, Colorectal Neoplasms, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Niacinamide/administration & dosage/analogs & derivatives, Population, Colorectal Neoplasms/*drug therapy/genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Irinotecan, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), Internal medicine, Proto-Oncogene Proteins, medicine, Humans, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, education, neoplasms, Aged, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, digestive system diseases, Surgery, KRAS gene mutation, Regimen, Phenylurea Compounds/administration & dosage, Clinical Study, ras Proteins, Proto-Oncogene Proteins/*genetics, Camptothecin, business
Abstract: IMPACT: 5.922; International audience; BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).
Published: 2014

41. Clinical Benefit of Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma: The French Retrospective SECTOR Study

Author: Brigitte Laguerre, François Bidault, Florence Joly, Nadine Houédé, Nadia Kelkouli, Oliver Lucidarme, Bernard Escudier, Stéphane Oudard, Lionnel Geoffrois, K. Slimane, Marine Gross-Goupil, Yann Vano, Philippe Barthélémy, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Bordeaux [Bordeaux], Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Novartis Pharma S.A.S., Oncologie génito-urinaire, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Novartis France SAS
Subjects: Male, Oncology, mTOR inhibitor, Phases of clinical research, Pharmacology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, chemistry.chemical_compound, 0302 clinical medicine, Renal cell carcinoma, Observational study, Clinical endpoint, 030212 general & internal medicine, Neoplasm Metastasis, Aged, 80 and over, Real-world study, Middle Aged, Kidney Neoplasms, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, Nivolumab, medicine.drug, Adult, medicine.medical_specialty, Cabozantinib, Urology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Everolimus, Carcinoma, Renal Cell, Aged, Retrospective Studies, VEGFR inhibitor, business.industry, Sequential targeted therapy, medicine.disease, Survival Analysis, Confidence interval, respiratory tract diseases, chemistry, business
Abstract: International audience; BACKGROUND:Real-world data of everolimus after vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy in metastatic renal cell carcinoma (mRCC) are limited.PATIENTS AND METHODS:The retrospective, noninterventional SECTOR (SECond line with afiniTOR) study (N = 165) assessed outcomes of second-line everolimus after initial VEGFR-TKI (TKI-everolimus, n = 144) and of third-line VEGFR-TKI after everolimus (TKI-everolimus-TKI, n = 59) in patients with mRCC. The primary end point was duration of everolimus therapy for both populations.RESULTS:Median duration was 4.0 months (range, 0.0-33.0 months) for second-line everolimus and 18.0 months (range, 2-78 months) for sequential VEGFR-TKI and everolimus. Median overall survival (OS) for this sequence was 36.0 months (95% confidence interval [CI], 27.0-56.0 months) and was longer for patients who received a first-line TKI for ≥ 9 months (not reached) than for < 9 months (28.0 months; P < .001). During second-line everolimus treatment, commonly reported adverse events (all grades) were fatigue (n = 66, 40.7%), anemia (n = 58, 35.8%), and stomatitis (n = 41, 25.3%). Median duration from initiation of first-line TKI to the end of the third-line TKI was 24.0 months (95% CI, 19.0-29.0 months). Median OS for this sequence was 41.0 months (95% CI, 25.0-57.0 months) and was significantly longer for patients who received the first-line TKI for ≥ 9 months (37.5 months) than for < 9 months (19.0 months; P < .0001).CONCLUSION:These results reflect clinical use of sequential TKI-everolimus and TKI-everolimus-TKI and provide additional evidence that everolimus could be an option in second-line therapy in mRCC. Results of the CheckMate-025 (Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma) and METEOR (Metastatic RCC Phase 3 Study Evaluating Cabozantinib versus Everolimus) studies might change the treatment landscape.
Published: 2016

42. Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

Author: Carole Tarpin, Sophie Paget-Bailly, Xavier Pivot, David Assouline, Maria Rios, Isabelle Tennevet, Gilles Romieu, Jean-Marc Ferrero, Céline Faure-Mercier, Pierre Fumoleau, Jean-François Deleuze, David G. Cox, Hélène Blanché, Marie-Christine Mathieu, Thierry Petit, Christelle Jouannaud, Hugues Bourgeois, Oana Cojocarasu, Thomas Bachelot, Elsa Curtit, Jérôme Meunier, Ariane Darut-Jouve, Delphine Bacq, Jean-Yves Pierga, Sandrine Lavau-Denes, Iris Pauporté, Valérie Delecroix, Christelle Levy, Patrick Soulié, Pierre Kerbrat, Véronique Trillet-Lenoir, Anne Boland, Hervé Bonnefoi, Mourad Sahbatou, Gilles Thomas, Jean-Philippe Jacquin, Julie Henriques, Céline Besse, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Institut Régional Fédératif du Cancer (IRFC)-Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Département de Cancérologie Médicale [Lyon], Centre Léon Bérard : Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes, Service Oncologie Médicale [Angers], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Service Oncologie Médicale [Reims], Institut Jean Godinot [Reims], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Service d’Oncologie Médicale [Strasbourg], Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service Oncologie Médicale [Grenoble], Institut Daniel Hollard [Grenoble], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service Oncologie Médicale [Saint Priest en Jarez], Institut de Cancérologie Lucien Neuwirth [Saint Priest en Jarez], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre d'oncologie et de radiothérapie du parc [Dijon], Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département d’Oncologie Médicale [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Oncologie Médicale [Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Oncologie Médicale [Saint-Nazaire] (Pôle Mutualiste), Centre Etienne Dolet [Saint-Nazaire], Service d’Oncologie Médicale [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’Onco-Hématologie et Médecine interne [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service d’Oncologie médicale [Orleans], Centre Hospitalier Régional d'Orléans (CHRO), Département d'Oncologie Médicale [Paris], Institut Curie [Paris], Service d'Oncologie Médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Direction de la Recherche [Boulogne-Billancourt], Institut National du Cancer [Boulogne Billancourt] (INC), Centre de Ressources Biologiques [Paris], Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Centre de Ressources Biologiques [Evry], Centre National du Génotypage [Evry], Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has fully been funded by the sponsor of the study, l’Institut National du Cancer, France (INCa)., Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'Oncologie Médicale [Besançon], Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz [Besançon], Unité de Méthodologie et de Qualité de Vie en Cancérologie ( UMQVC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Pôle cancérologie (CHU Besançon), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut Régional Fédératif du Cancer ( IRFC ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Institut Bergonié - CRLCC Bordeaux, UNICANCER - Institut de cancérologie de l'Ouest - Paul Papin [Angers], Centre Jean Bernard [Le Mans], Clinique Victor Hugo [Le Mans], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre d’oncologie et de radiothérapie du Parc [Dijon], Clinique Drévon [Dijon], UNICANCER - Centre Antoine Lacassagne [Nice], Institut Paoli-Calmettes [Marseille], Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Service Oncologie Médicale [Saint-Nazaire] ( Pôle Mutualiste ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Le Mans, Centre Hospitalier Régional d'Orléans ( CHR ), Institut Curie (Paris), CRLCC Eugène Marquis ( CRLCC ), Institut National du Cancer [Boulogne Billancourt] ( INC ), Centre d’Etudes du Polymorphisme Humain [Paris], Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, BMC, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Polyclinique du Parc - Clinique Drevon [Dijon], Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 0301 basic medicine, Oncology, [SDV]Life Sciences [q-bio], Metastasis, Cohort Studies, 0302 clinical medicine, Breast cancer, Neoplasm Metastasis, Prospective cohort study, Estrogen Receptor Status, Genetic variant, Randomized Controlled Trials as Topic, Aged, 80 and over, Framingham Risk Score, Middle Aged, Prognosis, Tumor Burden, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Female, Research Article, Adult, medicine.medical_specialty, Genotype, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Neoplasm Staging, [ SDV ] Life Sciences [q-bio], business.industry, Cancer, medicine.disease, Survival Analysis, Single nucleotide polymorphism, 030104 developmental biology, Clinical Trials, Phase III as Topic, Risk score, Neoplasm Grading, business
Abstract: Background Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. Methods A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. Results The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1–97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. Conclusions In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients’ outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. Trial registration PHARE cohort: NCT00381901, Sept. 26, 2006 – SIGNAL cohort: INCa RECF1098, Jan. 28, 2009 Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0888-4) contains supplementary material, which is available to authorized users.
Published: 2016

43. Sarcomes développés en territoire irradié : résultats préliminaires de l’étude SARI

Author: Maingon , Philippe, Mirjolet , Céline, Diallo , Ibrahima, Veres , Cristina, Collin , Françoise, Italiano , Antoine, Chibon , Frédéric, Merlin , Jean-Louis, Coindre , Jean-Michel, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Validation et identification de nouvelles cibles en oncologie (VINCO), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut Gustave Roussy ( IGR ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Bergonié, Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL )
Subjects: Male, Clinical Trials as Topic, Neoplasms, Radiation-Induced, Sarcomes en territoire irradié, Radiotherapy, Carcinogenesis, Neoplasms, Second Primary, Sarcoma, Soft Tissue Neoplasms, Middle Aged, Cancérogénèse, [SPI.AUTO]Engineering Sciences [physics]/Automatic, [ SPI.AUTO ] Engineering Sciences [physics]/Automatic, Radio-induced sarcoma, Humans, Female, Late toxicity, Complications tardives de la radiothérapie, Radiothérapie
Abstract: International audience; Radiotherapy and surgery are the two main pillars of the locoregional treatment of cancer. The risk of second malignancy is better evaluated and constitutes a major issue regarding radioprotection of the patients. Among malignant disease observed in the surviving irradiated patients, the occurrence of sarcoma is a rare event but associated with a poor outcome since the 5 year overall survival is estimated at 10 to 35 %. The SARI protocol, written in 2011, included 120 patients and 240 controlled patients, irradiated in the same conditions but without sarcoma observed during the follow up. The main objective was to identify the clinical and biological factors associated with the occurrence of such a complication. The secondary objective was to identify the dosimetric characteristics of the treatment of the primary. Preliminary results will be presented during the 2016 meeting of the French radiation oncology society.; La radiothérapie constitue avec la chirurgie les deux piliers majeurs du traitement locorégional du cancer. Le risque de second cancer devient mieux évalué et représente un souci majeur en termes de radioprotection. Parmi les lésions malignes découvertes chez des patients traités, l’apparition d’un sarcome est un évènement rare mais de pronostic sombre puisque le taux de survie des patients est estimé entre 10 à 35 % à 5 ans. Le protocole SARI, conçu et écrit en 2011, a permis l’inclusion de 120 patients atteints d’un sarcome développé en territoire irradié appariés à 240 témoins, irradiés dans les mêmes conditions, mais sans avoir vu se développer la maladie. L’objectif principal de l’essai était de déterminer les facteurs de risque clinique et biologique prédictifs, de survenu d’un sarcome en territoire irradié. Les objectifs secondaires étaient de décrire les caractéristiques de la radiothérapie chez l’ensemble des patients ayant vu se développer un sarcome sur territoire irradié. Les résultats préliminaires seront présentés lors du congrès 2016 de la Société française de radiothérapie oncologie.
Published: 2016

44. Treatment of Vulvar Intraepithelial Neoplasia With CO2 Laser Vaporization and Excision Surgery

Author: Philippe Rauch, François Guillemin, Pauline Baermann, Lina Bezdetnava, Frédéric Marchal, Emmanuel Desandes, Léa Leufflen, Thierry Routiot, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service de Chirurgie Gynécologique [Maternité Régionale - CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Adult, medicine.medical_specialty, Current smoker, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cold knife, 03 medical and health sciences, 0302 clinical medicine, Co 2 laser, Vaporization, Secondary Prevention, medicine, Humans, Aged, Retrospective Studies, Univariate analysis, 030219 obstetrics & reproductive medicine, Invasive carcinoma, Vulvar Neoplasms, business.industry, Obstetrics and Gynecology, General Medicine, Middle Aged, Vulvar intraepithelial neoplasia, medicine.disease, 3. Good health, Surgery, Laser vaporization, Treatment Outcome, Surgical Procedures, Operative, 030220 oncology & carcinogenesis, Female, Laser Therapy, business, Carcinoma in Situ
Abstract: International audience; OBJECTIVE: To evaluate the recurrence rate after a single treatment of vulvar intraepithelial neoplasia (VIN) with CO2 laser vaporization. MATERIALS AND METHODS: Fifty women with usual-type or differentiated VIN (grades 2 and 3) treated with CO2 laser vaporization or surgery excision (cold knife or CO2 laser) were retrospectively evaluated. RESULTS: Of the 50 patients, 41 (82.0%) had usual-type VIN and 9 (18.0%) had differentiated VIN. Moreover, 24 (48.0%) were treated with surgery excision and 26 (52.0%) underwent CO2 laser vaporization. Laser-treated patients were significantly younger (p < .01) with more multifocal (p < .05) and multicentric lesions (p < .01) than in the surgery group. Recurrence-free survival (RFS) rates at 1 year were 91.0% for the surgery and 65.2% for the laser vaporization groups (p < .01). At 5 years, RFS rates were unchanged for the surgery group and dropped to 51.3% (p < .01) for the laser group. On the univariate analysis, current smoker (p = .03), multicentric VIN (p = .02), and laser vaporization treatment (p < .01) had a statistically significant impact on RFS. One patient progressed to invasive cancer (2%). CONCLUSIONS: The recurrence rate after CO2 laser vaporization requires regular, close, and extended monitoring.
Published: 2013

45. Psychometric evaluation of the EORTC computerized adaptive test (CAT) fatigue item pool

Author: Teresa Young, Thierry Conroy, Eva-Maria Gamper, Morten Petersen, Bernhard Holzner, Madeleine King, Juan Ignacio Arraras, Johannes M. Giesinger, Irma M. Verdonck-de Leeuw, Mogens Groenvold, Bispebjerg Hospital, University of Copenhagen = Københavns Universitet (KU), Department of Psychiatry and Psychotherapy, Innsbruck Medical University [Austria] (IMU), Clínica Universidad de Navarra [Pamplona], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), The University of Sydney, Vrije Universiteit Amsterdam [Amsterdam] (VU), Mount Vernon Cancer Centre, Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Clinical Psychology, EMGO+ - Mental Health, Otolaryngology / Head & Neck Surgery, EMGO - Mental health, CCA - Quality of life, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: Male, MESH: Fatigue, Psychometrics, Item bank, MESH: Aged, 80 and over, 0302 clinical medicine, Quality of life, Neoplasms, Surveys and Questionnaires, Item response theory, MESH: Neoplasms, 030212 general & internal medicine, Fatigue, Aged, 80 and over, MESH: Aged, Item pool, MESH: Middle Aged, Middle Aged, humanities, 3. Good health, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, Psychology, Algorithms, Clinical psychology, Adult, medicine.medical_specialty, Adolescent, MESH: Factor Analysis, Statistical, MESH: Algorithms, behavioral disciplines and activities, Young Adult, MESH: Software, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, MESH: Psychometrics, SDG 3 - Good Health and Well-being, medicine, Humans, MESH: Surveys and Questionnaires, Aged, Quality of Life Research, MESH: Adolescent, MESH: Humans, Public Health, Environmental and Occupational Health, MESH: Quality of Life, MESH: Adult, Differential item functioning, MESH: Male, Quality of Life, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Computerized adaptive testing, Factor Analysis, Statistical, MESH: Female, Software
Abstract: Purpose: Fatigue is one of the most common symptoms associated with cancer and its treatment. To obtain a more precise and flexible measure of fatigue, the EORTC Quality of Life Group has developed a computerized adaptive test (CAT) measure of fatigue. This is part of an ongoing project developing a CAT version of the widely used EORTC QLQ-C30 questionnaire. Methods: Based on the literature search and evaluations by experts and patients, 41 new fatigue items were developed (in addition to the three QLQ-C30 fatigue items). Psychometric properties of the items, including evaluations of dimensionality, fit to item response theory (IRT) model, and differential item functioning (DIF), were assessed in an international sample of cancer patients. Results: Responses were obtained from 1,321 cancer patients coming from eight countries. Factor analysis showed that 37 of the items could be included in a unidimensional model (RMSEA = 0.098, TLI = 0.995, CFI = 0.920). Of the 37 items, two were deleted because of poor fit to the IRT model forming the basis for the CAT, and one because of DIF between cancer sites. Conclusions: We have established a 34-item fatigue bank allowing for more precise and flexible measurement of fatigue, while still being backward compatible with the QLQ-C30 fatigue scale. © Springer Science+Business Media Dordrecht 2013.
Published: 2013

46. The SCOPE of definitive chemoradiotherapy in locally advanced esophageal cancer: what direction for the future?

Author: Gilles Créhange, Thierry Conroy, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Laboratoire Electronique, Informatique et Image [UMR6303] ( Le2i ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-École Nationale Supérieure d'Arts et Métiers ( ENSAM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 )
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, Locally advanced, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Outcomes, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Intensity-Modulated Radiotherapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Carcinoma, Medicine, ComputingMilieux_MISCELLANEOUS, Capecitabine, Cisplatin, Chemotherapy, business.industry, Induction Chemotherapy, Esophageal cancer, medicine.disease, Radiation-Therapy, 3. Good health, Radiation therapy, Editorial, 030104 developmental biology, Chemoradiation, Fluorouracil, 030220 oncology & carcinogenesis, Ii Randomized-Trial, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Chemoradiotherapy, medicine.drug
Abstract: Exclusive chemoradiotherapy (CRT) delivering 50 Gy over 5 weeks with cisplatin and fluorouracil-based chemotherapy is a cornerstone in locally advanced esophageal cancer or non-operable patients since the results of the pivotal study of US Intergroup RTOG-8501 (1). This trial has successfully demonstrated that some patients with esophageal carcinoma may be long-term survivors so that this treatment is now definitely accepted as curative (2). Nevertheless the prognosis is still very disappointing with a 5-year overall survival rate of approximately 25%. Attempts to improve overall survival by escalating the dose of radiotherapy with concurrent cisplatin and fluorouracil has been assessed in INT 0123 trial (3). Overall survival rate after 64.8 Gy was not superior or even lower to 50.4 Gy. This result precluded dose escalation in esophageal cancer for more than a decade. However, the results of these two studies established CRT with the 50.4 Gy dose as the standard of care in esophageal cancer.
Published: 2016

47. Current standards and new innovative approaches for treatment of pancreatic cancer

Author: Jean-Luc Van Laethem, Michel Ducreux, Ahmet Ayav, Florence Huguet, Jean-Baptiste Bachet, Caroline Caramella, Aurélien Lambert, Raphaël Maréchal, Thierry Conroy, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'oncologie-radiothérapie [CHU Tenon], CHU Tenon [AP-HP], Institut Gustave Roussy (IGR), Service de Gastro-Entérologie, d'Hépato-Pancréatologie et d'Oncologie Digestive - Endoscopie Digestive (hôpital Erasme), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d’Oncologie-Radiothérapie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], and Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles)
Subjects: 0301 basic medicine, Oncology, Cancer Research, Palliative care, Staging, FOLFIRINOX, medicine.medical_treatment, MESH: Therapies, Investigational, Targeted therapy, Imaging, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Molecular Targeted Therapy, Molecular Targeted Therapy, Precision Medicine, Neoadjuvant therapy, Therapies, Investigational, Palliative Care, MESH: Neoplasm Staging, Reference Standards, Neoadjuvant Therapy, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, MESH: Palliative Care, MESH: Reference Standards, MESH: Pancreatic Neoplasms, MESH: Neoplasm Recurrence, Local, medicine.drug, Diagnostic Imaging, medicine.medical_specialty, MESH: Neoadjuvant Therapy, Adenocarcinoma, MESH: Precision Medicine, 03 medical and health sciences, Pancreatic cancer, Internal medicine, medicine, Humans, Chemotherapy, Survival rate, Neoplasm Staging, MESH: Humans, Radiotherapy, business.industry, MESH: Diagnostic Imaging, MESH: Adenocarcinoma, medicine.disease, Gemcitabine, Pancreatic Neoplasms, Radiation therapy, 030104 developmental biology, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neoplasm Recurrence, Local, business
Abstract: International audience; Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.
Published: 2016

48. Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity

Author: Estelle Thebaud, Sandrine Pereira, Eric Lartigau, Aurélie Etaix, N. Chavaudra, Séverine Racadot, Eric Doré, Laurène Sonzogni, François Eschwege, Ronan Tanguy, Nicolas Foray, Amira Ziouéche, Adeline Granzotto, Pascal Pommier, Y. Pointreau, Claire Berger, Mélanie L. Ferlazzo, Coralie Moncharmont, Anne-Sophie Defachelles, Patrick Combemale, Yazid Belkacemi, Dominique Stoppa-Lyonnet, Guillaume Vogin, Marie-Thérèse Zabot, Marie-Pierre Sunyach, Mohamed Amine Benadjaoud, Stéphanie Guey, Céline Bourgier, Nicole Dalla Venezia, Daniel Orbach, Renaud de Crevoisier, Karim Malek, A. d’Hombres, Clément Devic, Edme-Philippe Canat, Marie-Virginie Moreau-Claeys, Abderraouf Radji, Isabelle Rouvet, Bertrand Fleury, Clémence Escoffier, P. Leblond, Ngoc-Hanh Hau-Desbat, Fabien Forcheron, Laurence Mengue-Bindjeme, Anne Vincent, Isabelle Martel-Lafay, Cyril Lervat, Line Claude, Jean-Léon Lagrange, Guy de Laroche, Jacques Balosso, Marie-Claude Biston, Christian Carrie, Didier Peiffert, Jean-Marc Simon, Larry Bodgi, Michel H. Bourguignon, Cécile Laude, Claude Malet, Jean Bourhis, Frederic Baleydier, Françoise Gilsoul, Pierre Verrelle, Florent de Vathaire, Aurélie Joubert, Muriel Viau, Alain Puisieux, Loïc Feuvret, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biotechnologie cellulaire, Hospices Civils de Lyon (HCL), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Département de Pédiatrie, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Radiosensibilité des tumeurs & tissus sains, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Service de Dermatologie, Centre Léon Bérard [Lyon], Réseau NF-Rhône-Alpin, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cancer Resistance Exploring and Targeting (CREaT), Université d'Auvergne - Clermont-Ferrand I (UdA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service de radiothérapie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Hôpital Henri Mondor, CHU de Grenoble radiothérapie, Ministère de la santé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Equipe2, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille Nord de France (COMUE)-UNICANCER, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Ciblage thérapeutique en Oncologie ( EA3738 ), Université Claude Bernard Lyon 1 ( UCBL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Oncologie Radiothérapique [CHU Pitié Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Cancer Resistance Exploring and Targeting ( CREaT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Center Oscar Lambret, CRLCC Oscar Lambret, Institut Gustave Roussy ( IGR ), Institut Universitaire de France ( IUF ), and Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. )
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Time Factors, DNA Repair, DNA repair, Biopsy, medicine.medical_treatment, Ataxia Telangiectasia Mutated Proteins, Radiation Tolerance, Cell Line, Histones, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Radioresistance, [ PHYS.PHYS.PHYS-MED-PH ] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], medicine, Humans, DNA Breaks, Double-Stranded, Radiology, Nuclear Medicine and imaging, Radiosensitivity, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Phosphorylation, Radiation Injuries, Skin, Cell Nucleus, Analysis of Variance, Micronucleus Tests, Radiation, medicine.diagnostic_test, business.industry, Common Terminology Criteria for Adverse Events, Fibroblasts, 3. Good health, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Skin biopsy, Micronucleus test, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: International audience; PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III)
Published: 2016

49. A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

Author: Marta Gut, Iris Pauporté, Cécile Mannina, Sancha Martin, Michael R. Stratton, Frédérique Penault-Llorca, Vincent Le Texier, Laurent Arnould, Pierre Saintigny, Marie-Christine Mathieu, P. Fumoleau, Xavier Pivot, Jean-François Deleuze, Hélène Blanché, Anthony Ferrari, Janice Kielbassa, Eskeatnaf Mulugeta, Olivier Tredan, Sandrine Boyault, Anne Vincent-Salomon, Thomas Bachelot, Emilie Thomas, Jean-Yves Pierga, Odette Mariani, Suzette Delaloge, Ivo Gut, Hervé Bonnefoi, Fabien Calvo, Frédéric Bibeau, Alain Viari, Serena Nik-Zainal, Anne-Sophie Sertier, Gilles Romieu, Maria Rios, Gaëtan MacGrogan, Jocelyne Jacquemier, Laurie Tonon, Gilles Thomas, Jean-Marc Ferrero, Isabelle Treilleux, Daniel Birnbaum, Catherine Bouteille, Carole Tarpin, Centre Léon Bérard [Lyon], Génétique et Biologie du Développement, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Gustave Roussy (IGR), Equipe de recherche sur les traitements individualisés des cancers (ERTICa), Université d'Auvergne - Clermont-Ferrand I (UdA), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Ressources Biologiques [Paris], Institut Curie [Paris], Département de pathologie, Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Department of Medical Oncology [Lyon], UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, UNICANCER, Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chirurgie gynécologique, mammaire et réparatrice [Saint-Etienne], Clinique Mutualiste Chirurgicale [Saint-Étienne], Direction de la recherche [Gustave Roussy], Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), The Wellcome Trust Sanger Institute [Cambridge], Institut National du Cancer [Boulogne Billancourt] (INC), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Institut Gustave Roussy ( IGR ), Equipe de recherche sur les traitements individualisés des cancers ( ERTICa ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), UNICANCER - Institut régional du Cancer [Montpellier] ( ICM ), Institut Curie, Institut Bergonié - CRLCC Bordeaux, Physico-Chimie-Curie ( PCC ), Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CRLCC Antoine Lacassagne, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université ( AMU ), Centre for Genomic Regulation [Barcelona] ( CRG ), Universitat Pompeu Fabra [Barcelona]-Centro Nacional de Analisis Genomico [Barcelona] ( CNAG ), Institut National du Cancer [Boulogne Billancourt] ( INC ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale ( ERABLE ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Nik-Zainal Abidin, Serena [0000-0001-5054-1727], Apollo - University of Cambridge Repository, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Sagot, Marie-France, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Institut Paoli Calmettes, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Paoli-Calmettes-Aix Marseille Université ( AMU ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, DNA Copy Number Variations, Receptor, ErbB-2, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Breast Neoplasms, Biology, Genome, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Germline mutation, Gene duplication, medicine, Humans, Copy-number variation, skin and connective tissue diseases, Genetics, Multidisciplinary, Whole Genome Sequencing, [ SDV ] Life Sciences [q-bio], Gene Expression Profiling, Estrogen Receptor alpha, Gene Amplification, General Chemistry, Amplicon, medicine.disease, 3. Good health, Gene expression profiling, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Human genome, Female, Receptors, Progesterone, Transcriptome
Abstract: HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal–basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage–fusion–bridge mechanism., Breast cancer is separated into multiple subtypes based on the expression of HER2 and hormone receptors. Here, the authors report the whole genome sequence of 64 HER2 positive tumours and show that these can be further separated into four groups with different gene expression profiles and genomic features.
Published: 2016

50. Rare RAS Mutations in Metastatic Colorectal Cancer Detected During Routine RAS Genotyping Using Next Generation Sequencing

Author: Marie Husson, Pierre Filhine-Tresarrieu, Agnès Leroux, Jean-Louis Merlin, Marie Rouyer, Romain Boidot, Cindy Dubois, Alexandre Harlé, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Chimiothérapie et réponse immunitaire anti-tumorale (U866, Cancer, équipe 1), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Lipides - Nutrition - Cancer (U866) ( LNC ), and Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA )
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Silent mutation, Cancer Research, Genotype, medicine.medical_treatment, medicine.disease_cause, Deep sequencing, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Pharmacology (medical), Neoplasm Metastasis, Genotyping, Mutation, business.industry, High-Throughput Nucleotide Sequencing, Molecular biology, Survival Analysis, 3. Good health, 030104 developmental biology, Genes, ras, Oncology, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, KRAS, business, Colorectal Neoplasms
Abstract: International audience; BackgroundOverall survival of metastatic colorectal cancer (mCRC) patients has been improved with the addition of targeted therapy such as anti-epithelial growth factor receptor monoclonal antibodies (anti-EGFR mAbs) to standard chemotherapy. Retrospective studies and randomized trials showed that the presence of RAS mutations was linked to the absence of clinical response to anti-EGFR mAbs. Patients harboring KRAS and NRAS mutations on exons 2, 3 or 4 have little or no benefit from anti-EGFR therapies. Polymerase chain reaction (PCR)-based assays are routinely used to assess KRAS and NRAS status, whereas deep sequencing with next generation sequencing (NGS) currently represents an alternative method.ObjectiveThe objective of our study was to identify KRAS and NRAS non-hotspot mutations using NGS of mCRC tumor samples.MethodDNA was extracted from 188 consecutive formalin-fixed paraffin embedded samples of histologically proven colorectal cancer tumor tissue from patients with mCRC. Following amplification, DNA was sequenced by ultra-deep pyrosequencing. Non-hotspot mutations identified by NGS (frequency of mutated allele range [1.8–70.6 %]) were confirmed by Sanger direct-sequencing when possible.ResultsNGS procedure was applicable in 94 % of the cases and detected mutations in 62 % of the samples. Nine uncommon mutational profiles were found with a frequency of mutated allele > 1 %. Silent mutations were found in 3.6 % of the samples. Mutations at or near functional domains of RAS proteins, other than defined hotspots, were found in 3.6 %. NGS proved to be accurate, sensitive and suitable for routine RAS genotyping.ConclusionClinical responses to anti-EGFR mAbs are potentially impaired in the presence of these uncommon RAS mutations.
Published: 2015

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