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1. Descriptive Cohort of French Patients Treated With Carbonetherapy Since October 2010 Outside PHRC-ETOILE (PRIMHADRON)

Author: Centre François Baclesse, Centre de lutte contre le cancer (CLCC)
Published: 2024

2. Rechallenge en sels de platine après radiochimiothérapie pour les récidives de carcinome épidermoïde des voies aérodigestives supérieures

Author: Anna Rose Johnson, B. Géry, Idlir Licaj, D. de Raucourt, Audrey Rambeau, Emmanuel Babin, Juliette Thariat, Radj Gervais, C. Florescu, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de recherche clinique [Centre François Baclesse], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Radiothérapie [Centre François Baclesse], Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], 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), and Chirurgie ORL et cervico-faciale [Centre François Baclesse]
Subjects: 0301 basic medicine, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Otorhinolaryngology, 030220 oncology & carcinogenesis, Surgery, 3. Good health
Abstract: Resume Objectifs Evaluer l’efficacite et la tolerance du rechallenge en sel de platine chez les patients presentant un carcinome epidermoide des voies aerodigestives superieures (CE VADS) recidivant apres une radiochimiotherapie a base de sels de platine. Materiel et methodes Nous avons inclus retrospectivement tout patient traite par polychimiotherapie a base de sels de platine entre 2007 et 2016 pour la prise en charge d’un CE VADS en recidive apres radiochimiotherapie a base de sels de platine (traitement exclusif ou postoperatoire). L’objectif principal etait le taux de controle de la maladie lors du rechallenge en platine. Resultats Quarante-cinq patients ont ete inclus. L’intervalle sans maladie, median apres la radiochimiotherapie, etait de 5,7 mois. Le taux de controle de la maladie lors du rechallenge platine etait de 40 %. La mediane de survie sans progression a la recidive etait 3,7 mois et la mediane de survie globale de 5,0 mois. Parmi les patients presentant une recidive dans les 6 mois suivant la radiochimiotherapie, le taux de controle de la maladie etait de 47,8 %. Un intervalle sans maladie ≥ 4,5 mois etait associe a un meilleur taux de controle de la maladie (28,5 % versus 54,8 %, p = 0,0311). Conclusion Le rechallenge en platine permet un taux interessant de controle de la maladie en situation de CE VADS recidivant apres radiochimiotherapie.
Published: 2019

3. Faisabilité de la radiochimiothérapie postopératoire des carcinomes épidermoïdes des voies aérodigestives supérieures à haut risque de récidive en pratique quotidienne

Author: M. de La Losa, B. Géry, M. Humbert, Audrey Rambeau, C. Florescu, Juliette Thariat, Chirurgie ORL et cervico-faciale [Centre François Baclesse], 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 d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], 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), Radiothérapie [Centre François Baclesse], and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: 0301 basic medicine, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 030104 developmental biology, 0302 clinical medicine, Otorhinolaryngology, 030220 oncology & carcinogenesis, Surgery, 3. Good health
Abstract: Resume Objectif Evaluer en pratique quotidienne la faisabilite de la radiochimiotherapie postoperatoire chez les patients traites pour un carcinome epidermoide des voies aerodigestives superieures (CEVADS) a haut risque de recidive. Methode Etude retrospective monocentrique. Tout patient traite par radiochimiotherapie postoperatoire a base de cisplatine pour un CEVADS a haut risque etait eligible. L’objectif principal etait d’evaluer le taux de realisation complete de la radiochimiotherapie postoperatoire et l’impact de divers facteurs cliniques. Les objectifs secondaires etaient de preciser l’impact de la realisation complete du traitement sur la survie et les toxicites aigues et tardives. Resultats Cent six patients ont ete inclus. Parmi les patients, 24,5 % avaient une comorbidite severe. La radiochimiotherapie etait realisee en integralite chez 61 patients (57,5 %). La radiotherapie etait suspendue pendant plus de 3 jours chez 16 patients (15,1 %). La troisieme cure de cisplatine concomitante ne pouvait etre realisee chez 34 patients (32,1 %). La diminution du debit de filtration glomerulaire pre-therapeutique (p = 0,003) etait significativement associee a un risque d’interruption de traitement tandis que des resultats suggestifs concernant ce risque d’interruption en cas d’amaigrissement > 5 % en cours de traitement (p = 0,026). La realisation complete de la radiochimiotherapie n’etait pas associee a une difference significative en termes de survie globale (p = 0,441) et de survie sans progression (p = 0,81). Une insuffisance renale sequellaire a ete retrouvee chez 14,9 % des patients. Dix cas (9,4 %) d’osteoradionecrose ont ete rapportes. Conclusion Le taux de realisation complete de la radiochimiotherapie postoperatoire etait comparable a celui des essais cliniques malgre les comorbidites frequentes et l’etat nutritionnel precaire. Un support nutritionnel precoce reste un point cle afin de permettre la realisation du traitement dans des conditions optimales.
Published: 2020

4. Place de la radiothérapie stéréotaxique pour la prise en charge des cancers de prostate oligométastatiques

Author: C. Loiseau, N. Allouache, E. Rapeaud, E. Meyer, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Physique médicale (radiophysique) [Centre François Baclesse]
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Urology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 3. Good health
Abstract: Resume La radiotherapie stereotaxique est une technique innovante de radiotherapie externe, permettant de delivrer de fortes doses de rayonnement en une fraction unique ou en quelques fractions, avec une precision maximale. Cette technique peu invasive peut etre proposee pour la prise en charge des metastases de cancer de prostate, permettant d’obtenir un excellent controle local. Differentes situations de cancer de prostate oligometastatique peuvent etre identifiees, selon l’atteinte synchrone ou metachrone, d’une part, et selon le statut d’hormonosensibilite, d’autre part. Les modalites modernes d’imagerie, et particulierement les nouveaux traceurs utilises en medecine nucleaire ont permis de mieux selectionner les patients oligometastatiques. Les donnees de la litterature, bien que preliminaires, suggerent qu’un traitement focal des oligometastases de cancer de prostate par radiotherapie stereotaxique pourrait avoir un impact sur le pronostic des patients et permettre dans certains cas une epargne therapeutique, avec un profil de toxicite favorable. Les indications therapeutiques doivent etre proposees au cas par cas chez des patients rigoureusement selectionnes.
Published: 2020

5. Routine feasibility of postoperative chemoradiotherapy in head and neck squamous cell carcinoma at high risk of recurrence

Author: Audrey Rambeau, Juliette Thariat, B. Géry, M. de La Losa, C. Florescu, M. Humbert, Chirurgie ORL et cervico-faciale [Centre François Baclesse], 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 d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], 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), Radiothérapie [Centre François Baclesse], Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: medicine.medical_specialty, Osteoradionecrosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030223 otorhinolaryngology, Retrospective Studies, 2. Zero hunger, business.industry, Squamous Cell Carcinoma of Head and Neck, Retrospective cohort study, Chemoradiotherapy, medicine.disease, Comorbidity, Head and neck squamous-cell carcinoma, 3. Good health, Clinical trial, Radiation therapy, Otorhinolaryngology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Concomitant, Carcinoma, Squamous Cell, Feasibility Studies, Surgery, Neoplasm Recurrence, Local, business
Abstract: Objective To assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. Method A single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. Results One hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for > 3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p = 0.003) with treatment interruption; > 5% weight-loss during treatment showed suggestive association (p = 0.026). Completion of treatment was not associated with any significant difference in overall survival (p = 0.441) or progression-free survival (p = 0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). Conclusion The rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.
Published: 2020

6. Platinum rechallenge in recurrent head and neck squamous cell carcinoma after primary chemoradiation

Author: B. Géry, Idlir Licaj, Audrey Rambeau, Anna Rose Johnson, D. de Raucourt, Juliette Thariat, C. Florescu, Emmanuel Babin, Radj Gervais, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de recherche clinique [Centre François Baclesse], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Radiothérapie [Centre François Baclesse], Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cetuximab, chemistry.chemical_element, Gastroenterology, Disease-Free Survival, Carboplatin, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, 030223 otorhinolaryngology, Aged, Retrospective Studies, Cisplatin, Squamous Cell Carcinoma of Head and Neck, business.industry, Head and neck cancer, Chemoradiotherapy, Acute Kidney Injury, Middle Aged, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Otorhinolaryngology, chemistry, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, Surgery, Neoplasm Recurrence, Local, Previously treated, business, Platinum, medicine.drug
Abstract: Objective To evaluate platinum rechallenge efficacy and tolerance in patients presenting recurrent head and neck squamous cell carcinoma (HNSCC) after platinum-based chemoradiation. Materials and methods We retrospectively included all patients treated from 2007 to 2016 by platinum-based polychemotherapy for recurrence of HNSCC previously treated by primary or postsurgical platinum-based chemoradiation. The primary end-point was disease control rate (DCR) on platinum rechallenge. Results Forty-five patients were included. Median disease-free interval (DFI) after chemoradiation was 5.7 months. DCR on platinum rechallenge was 40%. Progression-free survival at recurrence was 3.7 months and overall survival 5.0 months. DCR in patients with recurrence within 6 months of chemoradiotherapy was 47.8%. DFI > 4.5 months was associated with better DCR: 28.5% versus 54.8%; P = 0.0311. Conclusion Platinum rechallenge provided good DCR in recurrent HNSCC after chemoradiation.
Published: 2019

7. Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma

Author: Bonvalot, S., Rutkowski, P.L., Thariat, J., Carrere, S., Ducassou, A., Sunyach, M.P., Agoston, P., Hong, A.M., Mervoyer, A., Rastrelli, M., Moreno, V., Li, R.K., Tiangco, B.J., Herra, A.C., Gronchi, A., Sy-Ortin, T., Hohenberger, P., Baere, T. de, Cesne, A. le, Helfre, S., Saada-Bouzid, E., Anghel, R.M., Kantor, G., Montero, A., Loong, H.H., Verges, R., Kacso, G., Austen, L., Servois, V.F., Wardelmann, E., Dimitriu, M., Said, P., Lazar, A.J., Bovee, J.V.M.G., Pechoux, C. le, Papai, Z., Institut Català de la Salut, [Bonvalot S] Department of Surgical Oncology, Institut Curie, Paris University, Paris, France. [Rutkowski PL] Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. [Thariat J] Department of Radiation Oncology, Centre François Baclesse, Caen, France. Department of Radiation Oncology, Centre Lacassagne, Nice, France. [Carrère S] Department of Surgical Oncology, Centre Regional De Lutte Contre Le Cancer Paul Lamarque, Montpellier, France. [Ducassou A] Department of Radiation Oncology, Institut Claudius Regaud (ICR), Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O), Toulouse, France. [Sunyach MP] Department of Radiotherapy, Léon Bérard Cancer Center, Lyon, France. [Vergés R] Servei d’Oncologia Radioteràpica, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adult, Cancer Research, Càncer - Radioteràpia, Radiation, Other subheadings::Other subheadings::/radiotherapy [Other subheadings], Otros calificadores::Otros calificadores::/radioterapia [Otros calificadores], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Soft Tissue Neoplasms [DISEASES], Antineoplastic Agents, Sarcoma, Soft Tissue Neoplasms, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Tumors de parts toves - Tractament, Neoadjuvant Therapy, Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Oncology, Avaluació de resultats (Assistència sanitària), Quality of Life, Humans, terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Radiology, Nuclear Medicine and imaging, Radiopharmaceuticals, neoplasias::neoplasias por localización::neoplasias de los tejidos blandos [ENFERMEDADES]
Abstract: Calidad de vida; Sarcoma de tejido blando localmente avanzado; Radioterapia Qualitat de vida; Sarcoma de teixit tou localment avançat; Radioteràpia Quality of life; Locally advanced soft-tissue sarcoma; Radiation therapy Purpose Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. Methods and Materials Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. Results During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. Conclusions NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit–risk ratio of NBTXR3 plus RT.
Published: 2022

8. From precise surgery to precision surgery: The multiple dimensions of therapeutic precision for head and neck cancer

Author: Antoine Galmiche, Zuzana Saidak, Emmanuel Babin, Esteban Brenet, Julien Davrou, Isabelle Fournier, Bernard Devauchelle, Sylvie Testelin, Stephanie Dakpe, Adrien Pellet, Juliette Thariat, Vianney Bastit, Florian Clatot, Pierre Saintigny, Jebrane Bouaoud, Jean-Philippe Foy, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Département de chirurgie de la tête et du cou [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), Radiothérapie [Centre François Baclesse], Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Amiens-Picardie, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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 Lutte contre le Cancer Léon Bérard (CLB), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon
Subjects: Otorhinolaryngology, Head neck cancer, Surgery, Oral Surgery, Personalized medicine, Precision surgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2022

9. Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial

Author: Paul Nguyen, Guillaume Vogin, Ludovic Harzée, Philippe Nickers, Stéphane Joseph, Paul Retif, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Urogenital System, Urinary incontinence, Radiosurgery, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Quality of life, Cyberknife, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Aged, business.industry, Prostate, Prostatic Neoplasms, Common Terminology Criteria for Adverse Events, medicine.disease, 3. Good health, Radiation therapy, Regimen, Oncology, 030220 oncology & carcinogenesis, Cohort, Quality of Life, Radiology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: There are no safety-focused trials on stereotactic body radiotherapy (SBRT) for localized prostate cancer. This prospective 3‑year phase II trial used binomial law to validate the safety and efficacy of SBRT with stringent organ at risk dose constraints that nevertheless permitted high planning target volume doses.Methods: All consecutive ≥ 70-year-old patients with localized prostate adenocarcinoma who underwent SBRT between 2014 and 2018 at the National Radiotherapy Center in Luxembourg were included. Patients with low Cancer of Prostate Risk Assessment (CAPRA) scores (0–2) and intermediate scores (3–5) received 36.25 Gy. High-risk (6–10) patients received 37.5 Gy. Radiation was delivered in 5 fractions over 9 days with Cyberknife-M6™ (Accuray, Sunnyvale, CA, USA). Primary study outcome was Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) genitourinary and rectal toxicity scores at last follow-up. Based on binomial law, SRBT was considered safe in this cohort of 110 patients if there were ≤ 2 severe toxicity (CTCAEv4 grade ≥ 3) cases. Secondary outcomes were biochemical progression-free survival (bPFS) and patient quality of life (QOL), as determined by the IPPS and the Urinary Incontinence QOL questionnaire.Results: The first 110 patients who were accrued in a total cohort of 150 patients were included in this study and had a median follow-up of 36 months. Acute grade ≥ 3 toxicity never occurred. One transient late grade 3 case was observed. Thus, our SBRT program had an estimated severe toxicity rate of
Published: 2021

10. Investigating the effects of proton therapy versus X-rays on circulating leukocytes in a context of brain irradiation: a preclinical study

Author: Coupey, Julie, Pham, Thao Nguyen, Toutain, Jérôme, Hue, Erika, Hélaine, Charly, Richard, Jade, Saulnier, Romaric, Chazalviel, Laurent, Rousseau, Marc, Thariat, Juliette, Leblond, Marine M., Valable, Samuel, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: CERVOXY; National audience
Published: 2022

11. Comparative study of proton versus X-rays on circulating leukocytes in a context of brain irradiation: a preclinical study

Author: Coupey, Julie, Pham, Thao Nguyen, Toutain, Jérôme, Hue, Erika, Hélaine, Charly, Richard, Jade, Saulnier, Romaric, Chazalviel, Laurent, Rousseau, Marc, Thariat, Juliette, Leblond, Marine M., Valable, Samuel, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: CERVOXY; National audience
Published: 2022

12. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial

Author: François-Clément Bidard, Anne-Claire Hardy-Bessard, Florence Dalenc, Thomas Bachelot, Jean-Yves Pierga, Thibault de la Motte Rouge, Renaud Sabatier, Coraline Dubot, Jean-Sébastien Frenel, Jean Marc Ferrero, Sylvain Ladoire, Christelle Levy, Marie-Ange Mouret-Reynier, Alain Lortholary, Julien Grenier, Camille Chakiba, Laetitia Stefani, Jérôme Edouard Plaza, Florian Clatot, Luis Teixeira, Véronique D'Hondt, Hélène Vegas, Olfa Derbel, Claire Garnier-Tixidre, Jean-Luc Canon, Barbara Pistilli, Fabrice André, Laurent Arnould, Anne Pradines, Ivan Bièche, Céline Callens, Jérôme Lemonnier, Frédérique Berger, Suzette Delaloge, Francois-Clement BIDARD, Barbara PISTILLI, Florence DALENC, Thomas BACHELOT, Thibault DE LA MOTTE ROUGE, Renaud SABATIER, Coraline DUBOT, Jean-Sébastien FRENEL, Jean-Marc FERRERO, Sylvain LADOIRE, Christelle LEVY, Marie-Ange MOURET-REYNIER, Anne-Claire HARDY-BESSARD, Alain LORTHOLARY, Julien GRENIER, Camille CHAKIBA, Laetitia STEFANI, Patrick SOULIE, Jean-Philippe JACQUIN, Jérôme Edouard PLAZA, Florian CLATOT, Luis TEIXEIRA, Véronique D'HONDT, Hélène VEGAS, Olfa DERBEL, Claire GARNIER TIXIDRE, Catherine DELBALDO, Lionel MOREAU, Caroline CHENEAU, Jean-François PAITEL, Chantal BERNARD-MARTY, Dominique SPAETH, Dominique GENET, Isabelle MOULLET, Nathalie BONICHON-LAMICHHANE, Laura DEIANA, Charlotte GREILSAMER, Laurence VENAT-BOUVET, Valérie DELECROIX, Adrien MELIS, Hubert ORFEUVRE, Suzanne NGUYEN, Eric LEGOUFFE, Alain ZANNETTI, Romuald LE SCODAN, Nadine DOHOLLOU, Philippe DALIVOUST, Olivier ARSENE, Nathalie MARQUES, Thierry PETIT, Delphine MOLLON, Jérôme DAUBA, Nathalie BONNIN, François MORVAN, Miriam GARDNER, Adina MARTI, Charles-Briac LEVACHE, Emma LACHAIER, Mihaela ACHILLE, Christophe VALMAR, Ryan BOUAITA, Jacques MEDIONI, Cyril FOA, Francesco DEL PIANO, Michel GOZY, Anne ESCANDE, Nicolas LEDUC, Brigitte LUCAS, Dominique MILLE, Hanifa AMMARGUELLAT, Abeer NAJEM, Fanny TROUBOUL, Philippe BARTHELEMY, Hervé DESCLOS, Didier MAYEUR, Fabrice LORCHEL, François GUINET, Anne-Pascale LAURENTY, Axelle BOUDRANT, Olivier GISSEROT, Corinne ALLEAUME, Aimery DE GRAMONT, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Radiothérapie [Centre François Baclesse], 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), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital privé du Confluent [Nantes], Institut Sainte Catherine [Avignon], Institut Bergonié [Bordeaux], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cancer de Montpellier (ICM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital privé Jean Mermoz [Lyon], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL), and Pfizer
Subjects: Adult, Neutropenia, Adolescent, Aromatase Inhibitors, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Breast Neoplasms, Disease-Free Survival, Oncology, Receptors, Estrogen, Lymphopenia, Antineoplastic Combined Chemotherapy Protocols, Mutation, Humans, Female, Prospective Studies, Fulvestrant
Abstract: In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1Pfizer.
Published: 2022

13. Deep Hybrid Learning Prediction of Patient-Specific Quality Assurance in Radiotherapy: Implementation in Clinical Routine

Author: Noémie Moreau, Laurine Bonnor, Cyril Jaudet, Laetitia Lechippey, Nadia Falzone, Alain Batalla, Cindy Bertaut, Aurélien Corroyer-Dulmont, Physique médicale (radiophysique) [Centre François Baclesse], 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), GenesisCare, Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC), GIP Cyceron (Cyceron), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: clinical routine, machine learning, [SDV]Life Sciences [q-bio], deep hybrid learning, Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, VMAT, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, quality assurance, radiotherapy
Abstract: CERVOXY; International audience; Background: Arc therapy allows for better dose deposition conformation, but the radiotherapy plans (RT plans) are more complex, requiring patient-specific pre-treatment quality assurance (QA). In turn, pre-treatment QA adds to the workload. The objective of this study was to develop a predictive model of Delta4-QA results based on RT-plan complexity indices to reduce QA workload. Methods. Six complexity indices were extracted from 1632 RT VMAT plans. A machine learning (ML) model was developed for classification purpose (two classes: compliance with the QA plan or not). For more complex locations (breast, pelvis and head and neck), innovative deep hybrid learning (DHL) was trained to achieve better performance. Results. For not complex RT plans (with brain and thorax tumor locations), the ML model achieved 100% specificity and 98.9% sensitivity. However, for more complex RT plans, specificity falls to 87%. For these complex RT plans, an innovative QA classification method using DHL was developed and achieved a sensitivity of 100% and a specificity of 97.72%. Conclusions. The ML and DHL models predicted QA results with a high degree of accuracy. Our predictive QA online platform is offering substantial time savings in terms of accelerator occupancy and working time.
Published: 2023

14. A Quantitative Comparison between Shannon and Tsallis–Havrda–Charvat Entropies Applied to Cancer Outcome Prediction

Author: Thibaud Brochet, Jérôme Lapuyade-Lahorgue, Alexandre Huat, Sébastien Thureau, David Pasquier, Isabelle Gardin, Romain Modzelewski, David Gibon, Juliette Thariat, Vincent Grégoire, Pierre Vera, Su Ruan, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, du Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Aquilab, Radiothérapie [Centre François Baclesse], 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), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Equipe Quantification en Imagerie Fonctionnelle [QuantIF-LITIS], and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, deep neural networks, Shannon entropy, Tsallis–Havrda–Charvat entropy, generalized entropies, recurrence prediction, head–neck cancer, lung cancer, [SDV]Life Sciences [q-bio], Image and Video Processing (eess.IV), Physics::Medical Physics, General Physics and Astronomy, Electrical Engineering and Systems Science - Image and Video Processing, Machine Learning (cs.LG), FOS: Electrical engineering, electronic engineering, information engineering
Abstract: In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis-Havrda-Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head-neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis-Havrda-Charvat cross-entropy is a parameterized cross entropy with the parameter $\alpha$. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy for $\alpha$ = 1. The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head-neck cancers and 146 from lung cancers. The results show that Tsallis-Havrda-Charvat entropy can achieve better performance in terms of prediction accuracy with some values of $\alpha$., Comment: 11 pages, 3 figures
Published: 2022

15. Social and sexual health of thyroid cancer survivors 2 and 5 years after diagnosis: the VICAN survey

Author: Franck Jegoux, Gwenaelle Creff, Emmanuel Babin, Idlir Licaj, Marc-Karim Bendiane, Service d'ORL et de chirurgie maxillo-faciale [Rennes] = ENT Head and Neck Surgery [Rennes], CHU Pontchaillou [Rennes], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de chirurgie de la tête et du cou [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), Radiothérapie [Centre François Baclesse], The Arctic University of Norway [Tromsø, Norway] (UiT), and Dupuis, Christine
Subjects: Adult, Quality of life, media_common.quotation_subject, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Orgasm, Human physical appearance, Cancer Survivors, Surveys and Questionnaires, Sexual desire, Medicine, Humans, Thyroid Neoplasms, Survivors, Depression (differential diagnoses), media_common, Reproductive health, business.industry, Incidence (epidemiology), Thyroidectomy, Thyroid cancer, [SDV] Life Sciences [q-bio], Oncology, Female, Sexual Health, business, Demography
Abstract: International audience; Purpose: Thyroid cancer (TC) incidence is increasing. With its good prognosis and the young population concerned, the number of survivors is rising. However, their quality of life appears worse than expected. This study aims to assess the social and sexual health (SSH) of TC survivors and associated factors after a 2- and 5-year follow-up.Methods: This study belongs to the National VICAN Survey implemented in France among TC patients diagnosed between January and June 2010. Data were collected via phone interviews, medical surveys, and from medico-administrative register in 2012 and 2015. We used multivariable logistic regressions to qualify TC impact on SSH.Results: Across 146 patients, 121 were women, 50.7% were less than 42 years old, 77.5% were diagnosed at an early-stage, and 97.6% underwent thyroidectomy. At 2 years, 60.0% experienced social life discomfort because of cancer, 40.6% reported a decreased sexual desire, 37.4% fewer intercourse, 31.9% felt dissatisfied with this frequency, 30% reported difficulties achieving orgasm, and 15.2% considered that cancer had a negative influence for procreation. No significant difference was observed at 5 years. SSH was never discussed with medical professionals for 96.7% patients, as it was not proposed as a topic of concern (79.1%). In multivariable analysis, depression, embarrassment regarding their physical appearance since treatment, and reduced gestures of affection remained associated with decreased sexual desire.Conclusion: This study highlights that TC is associated with an alteration of SSH which remains even at 5 years post-diagnosis. SSH should be discussed during diagnosis and considered during follow-up.
Published: 2022

16. Cognitive Impairment in Older Cancer Patients Treated with First-Line Chemotherapy

Author: Mélanie Dos Santos, Idlir Licaj, Carine Bellera, Laurent Cany, Giulia Binarelli, Pierre Soubeyran, Florence Joly, Service de recherche clinique [Centre François Baclesse], 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), 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), The Arctic University of Norway [Tromsø, Norway] (UiT), 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), Institut Bergonié [Bordeaux], UNICANCER, and Admin, Oskar
Subjects: Cancer Research, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, geriatric assessment, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy, elderly, Article, cancer, cognitive impairment, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, RC254-282, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Abstract: Simple Summary Chemotherapy-related cognitive impairment is frequently reported by patients and can have a negative impact on their quality of life. Elderly patients appear to be particularly at risk for cognitive decline but they are rarely included in studies. Our study investigated cognitive impairment during chemotherapy and its predictive factors among a large elderly population (≥70 years) treated with first-line chemotherapy. The aim was to identify risk factors before starting chemotherapy in order to manage and help elderly patients with decision making. Abstract Older cancer patients are vulnerable to chemotherapy-related cognitive impairment. We prospectively evaluated cognitive impairment and its predictive factors during first-line chemotherapy in elderly cancer patients (≥70 years). Cognitive function was evaluated by the Mini-Mental State Examination (MMSE) with adjusted scores for age and sociocultural level. Multidimensional geriatric assessment was performed at baseline and during chemotherapy including the MMSE, Instrumental Activities in Daily Living (IADL), Mini-Nutritional Assessment (MNA), and the Geriatric Depression Scale (GDS15). Quality of life (QoL) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ-C30). Of 364 patients included, 310 had two MMSE evaluations including one at baseline and were assessed. Among these patients, 86 (27.7%) had abnormal MMSE, 195 (62.9%) abnormal MNA, 223 (71.9%) abnormal IADL, and 137 (43.1%) had depressive symptoms at baseline. MMSE impairment during chemotherapy was observed in 58 (18.7%) patients. Abnormal baseline MNA (odds ratio (OR) = 1.87, p = 0.021) and MMSE (OR = 2.58, p = 0.022) were independent predictive factors of MMSE impairment. These results suggest that pre-existing cognitive impairment and malnutrition are predictive factors for cognitive decline during chemotherapy in elderly cancer patients. Detection and management of these risk factors should be systematically considered in this population before starting chemotherapy.
Published: 2021

17. Impact d’un algorithme de machine learning de resampling sur les radiomiques en IRM

Author: Moummad, I, Jaudet, C, Lechervy, A, Valable, S, Raboutet, C, Lacroix, J, Batalla, A, Corroyer-Dulmont, A, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Brunaud, Carole, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Physique médicale (radiophysique) [Centre François Baclesse], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Service de Radiologie [CLCC Baclesse], Equipe Image - Laboratoire GREYC - UMR6072, Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: CERVOXY; National audience
Published: 2021

18. The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice

Author: Laurence Desrues, Marie Lange, Ludovic Galas, Florence Joly, Hélène Castel, Martine Dubois, C. Nicola, Damien Schapman, T. Al Sagheer, Cynthia Campart, Lebon, Alexis, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Service de recherche clinique [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, metastatic resistant prostate cancer, [SDV]Life Sciences [q-bio], Substantia nigra, abiraterone acetate/prednisone, Article, Androgen deprivation therapy, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Internal medicine, medicine, Enzalutamide, RC254-282, enzalutamide, business.industry, Pars compacta, behavior, Dopaminergic, Abiraterone acetate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, dopaminergic pathways, aged castrated mice, medicine.disease, [SDV] Life Sciences [q-bio], Ventral tegmental area, medicine.anatomical_structure, chemistry, Dopaminergic pathways, 030220 oncology & carcinogenesis, business, 030217 neurology & neurosurgery
Abstract: Simple Summary Cognitive side effects and fatigue after cancer treatment now constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are next-generation therapies improving metastatic castration-resistant prostate cancer (mCRPC) patient survival, but also associated with neurological disturbances. We developed a behavioral 17 months-aged and castrated mouse model receiving AAP or ENZ for 5 days per week for six weeks. We establish that ENZ impacts locomotor and explorative behaviors, and strength capacity likely by preventing binding of central synthetized androgens to androgen receptors expressed by dopamine neurons of the Substantia Nigra and the Ventral Tegmentum. ENZ also reduces the cognitive score, associated with less neuronal activity in dorsal hippocampal areas. This demonstrates ENZ-specific consequences on motivation to exploration and cognition, being of particular importance for future management of elderly prostate cancer patients and their quality of life. Abstract Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment were reported. We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ for 5 days per week for six consecutive weeks. ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH+-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN+-neurons in the dorsal hippocampus. The consequences of the mCRPC treatment ENZ on aged castrated mouse motivation to exploration and cognition should make reconsider management strategy of elderly prostate cancer patients.
Published: 2021

19. Identification and genetic characterization of equine infectious anemia virus in Western Balkans

Author: Nicolas Berthet, Aymeric Hans, Sara Savić, Diana Lupulović, Živoslav Grgić, D. Gaudaire, Kazimir Matović, Alexandre Deshiere, Scientific Veterinary Institute 'Novi Sad', Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], This study was supported by the Hubert Curien Partnerships (PHC-Pavle Savic), the European Reference Laboratory for Equine Diseases other than African Horse Sickness, ANSES’s own institutional resources and the Ministry of Science and Technological Development of the Republic of Serbia (Grant no. TR31071). Alexandre Deshiere and 'CENTAURE project' was supported by a grant awarded by the Regional Council of Normandy and the French Ministry of Higher Education, within the framework of CPER 2015–2020 and FEDER/FSE 2014–2020. Nicolas Berthet is also supported by the Chinese Academy of Sciences and a Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication., The authors thank the sequencing platform SeSAME of the Centre François Baclesse in Caen, Normandy and official veterinary services in Serbia. Laboratoire de santé animale, site de Normandie is a member of the GIS Centaure equine research and authors thanks Regional Council of Normandy, France for providing an excellent scientific environment, and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: 040301 veterinary sciences, Veterinary medicine, [SDV]Life Sciences [q-bio], viruses, Population, Enzyme-Linked Immunosorbent Assay, Genome, Viral, Virus, Serology, 0403 veterinary science, Equine infectious anemia, 03 medical and health sciences, Seroepidemiologic Studies, SF600-1100, AGID test, Animals, MESH: Animals, Horses, education, MESH: Horses, MESH: Phylogeny, Phylogeny, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, education.field_of_study, MESH: Seroepidemiologic Studies, General Veterinary, biology, Horse, MESH: Enzyme-Linked Immunosorbent Assay, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, Ouchterlony double immunodiffusion, Virology, 3. Good health, MESH: Serbia, MESH: Equine Infectious Anemia, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Equine Infectious Anemia, NGS, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Infectious Anemia Virus, Equine, Viral disease, MESH: Genome, Viral, Serbia, Research Article, Infectious Anemia Virus, Equine
Abstract: Background Equine infectious anemia (EIA) is a viral disease, caused by the Equine Infectious Anemia virus (EIAV) belonging to the Retroviridae family, genus Lentivirus. Horses (or equids) infected with EIAV are lifelong carriers and they remain contagious for other horses even in the absence of clinical signs. So far, EIAV infection has been reported among horses in North and South America, France, Germany, Italy, Hungary and Romania, with no publication regarding the presence of EIAV in horses in Serbia. To determine the circulation of EIAV among, approximately, the 5000 horses of the Vojvodina region, northern part of Serbia, 316 serum undergone serological testing for EIA. Then, identification and full genome sequencing using next generation sequencing was performed from one EIA positive horse. Results the 316 sera were tested with 3 different commercial agar gel immunodiffusion (AGID) tests and two different commercial enzyme-linked immunosorbent assay (ELISA). With the three AGID kits, 311 (98.4%) among the 316 tested sera were negative and only five (1.6%) sera were positive for EIA. Some discrepancies were seen for the two ELISA kits tested since one exhibited the same results as AGID test and the second gave 295 sera with negative results, five with a positive result and 16 with doubtful outcome. Phylogenetic analysis performed using the full genome sequence showed that EIAV characterized from a horse in Serbia is different from those identify so fare around the world and form a distinct and separate group together with another EIAV strain. Conclusions This study demonstrate for the first time that EIAV is circulating at a low level in the horse population from the Northern part of Serbia. Interestingly, phylogenetic data indicates that this EIAV from the western Balkan region of Europe belongs to a new cluster.
Published: 2021

20. Sentinel node biopsy stands the test of time and the proof of time

Author: Bruno Guelfucci, O. Choussy, V. Bastit, Gilles Dolivet, Benjamin Lallemant, Sébastien Vergez, Jérôme Sarini, Valentin Favier, A. Moya Plana, Nicolas Fakhry, Gilles Poissonnet, Renaud Garrel, M. de Boutray, Salvy-Córdoba, Nathalie, Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Alexis Vautrin (CAV), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Institut Curie [Paris], Chirurgie ORL et cervico-faciale [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: medicine.medical_specialty, Skin Neoplasms, MESH: Sentinel Lymph Node Biopsy, MESH: Lymphatic Metastasis, Breast Neoplasms, MESH: Lymph Nodes, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biopsy, medicine, Humans, MESH: Humans, medicine.diagnostic_test, business.industry, Sentinel Lymph Node Biopsy, MESH: Skin Neoplasms, Sentinel node, Test (assessment), Otorhinolaryngology, Lymphatic Metastasis, Surgery, Female, Radiology, Lymph Nodes, business, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; Observational studies conducted in the 1970s, including that by Bernard Guerrier, cited by Bocca et al. [1], and subsequent studies published in the literature [2], have shown that neck dissection must be systematically performed in operable stage T1-T2N0 oral and oropharyngeal squamous cell carcinoma (OC) in order to diagnose and treat occult micrometastases [3].
Published: 2021

21. Radiation enteritis: Diagnostic and therapeutic issues

Author: Benjamin Menahem, Arnaud Alves, C. Florescu, L. Loge, Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Radiothérapie [Centre François Baclesse], 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), 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), Normandie simulation santé (NORSIMS), CCSD, Accord Elsevier, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: medicine.medical_specialty, Malabsorption, Fistula, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Perforation (oil well), 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Intestine, Small, medicine, Radiation Enteritis, Humans, Radiation Injuries, Abscess, 2. Zero hunger, Radiotherapy, business.industry, Malnutrition, Colonoscopy, General Medicine, medicine.disease, Short bowel syndrome, Combined Modality Therapy, Enteritis, 3. Good health, Discontinuation, Surgery, Radiation therapy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Tomography, X-Ray Computed, business
Abstract: Abdominal pelvic radiation therapy can induce acute or chronic lesions in the small bowel wall, called radiation enteritis. Treatment of acute radiation enteritis is essentially symptomatic; symptoms regress when radiation is discontinued. Conversely, late toxicity can occur up to 30 years after discontinuation of radiation therapy, posing diagnostic problems. Approximately one out of five patients treated by radiation therapy will present clinical signs of radiation enteritis, including obstruction, malabsorption, malnutrition and/or other complications. Management should be multidisciplinary, centered mainly on correction of malnutrition. Surgery is indicated in case of complications (i.e., abscess, perforation, fistula) and/or resistance to medical treatment; intestinal resection should be preferred over internal bypass. The main risk in case of iterative resections is the short bowel syndrome and the need for definitive nutritional assistance.
Published: 2020

22. Review of clinical applications of radiation-enhancing nanoparticles

Author: E. Chajon, Valentin Calugaru, N. Scher, C. Le Tourneau, Sylvie Bonvalot, Juliette Thariat, C. Verry, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, 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), Centre Eugène Marquis (CRLCC), CHU Grenoble, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Radiothérapie [Centre François Baclesse], 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), CCSD, Accord Elsevier, and MINES ParisTech - École nationale supérieure des mines de Paris
Subjects: 0106 biological sciences, Oncology, medicine.medical_specialty, Gadolinium, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Biotechnology, chemistry.chemical_element, Review Article, 01 natural sciences, Applied Microbiology and Biotechnology, 03 medical and health sciences, 010608 biotechnology, Internal medicine, lcsh:TP248.13-248.65, medicine, 030304 developmental biology, Radiothérapie, Cancer, Cervical cancer, 0303 health sciences, Radiotherapy, business.industry, Nanoparticules, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Clinical trial, Radiation therapy, [SDV] Life Sciences [q-bio], chemistry, Nanoparticles, Sarcoma, Liver cancer, business, Biotechnology
Abstract: Highlights • Inorganic nanoparticles activated by radiotherapy (RT) increase dose deposition within cancer cells compared to RT alone. • Recently, clinical evidence of the radiation-enhancing effects of NP has emerged. • Two radio-enhancement NP are currently under investigation in clinical trials: hafnium oxide NP and gadolinium-based NP. • So far, 229 patients have been treated with NP and RT for soft tissue sarcoma, head and neck cancers or liver cancer. • Intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma., Purpose Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. Materials and methods We searched the literature in English and French on PubMed up to October 2019. The search term was “nanoparticle” AND “radiotherapy”, yielding 1270 results. Results The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. Conclusion So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.
Published: 2020

23. Pharmacogenetic Study of Trabectedin-Induced Severe Hepatotoxicity in Patients with Advanced Soft Tissue Sarcoma

Author: Emmanuelle Bompas, Julien Plenecassagnes, Laure Gourdain, Antoine Italiano, Axel Le Cesne, Nicolas Penel, Corinne Delcambre-Lair, Etienne Chatelut, Caroline Delmas, Félicien Le Louedec, Manon Cassou, Fabienne Thomas, Stéphanie Foulon, Didier Cupissol, Maud Maillard, Christine Chevreau, Nicolas Isambert, Jean-Yves Blay, François Bertucci, C. Guillemet, 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, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), 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), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Bordeaux (UB), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Radiothérapie [Centre François Baclesse], 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), Université de Lille, 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, hepatotoxicity, Abcg2, [SDV.CAN]Life Sciences [q-bio]/Cancer, CYP450, 030226 pharmacology & pharmacy, Pharmacogenetic Study, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, medicine, Allele, Trabectedin, biology, business.industry, Soft tissue sarcoma, Odds ratio, advanced soft tissue sarcoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ABC transporters, 030220 oncology & carcinogenesis, trabectedin, biology.protein, pharmacogenetic, next-generation sequencing, business, Pharmacogenetics, medicine.drug
Abstract: Hepatotoxicity is an important concern for nearly 40% of the patients treated with trabectedin for advanced soft tissue sarcoma (ASTS). The mechanisms underlying these liver damages have not yet been elucidated but they have been suggested to be related to the production of reactive metabolites. The aim of this pharmacogenetic study was to identify genetic variants of pharmacokinetic genes such as CYP450 and ABC drug transporters that could impair the trabectedin metabolism in hepatocytes. Sixty-three patients with ASTS from the TSAR clinical trial (NCT02672527) were genotyped by next-generation sequencing for 11 genes, and genotype&ndash, toxicity association analyses were performed with R package SNPassoc. Among the results, ABCC2 c.1249A allele (rs2273697) and ABCG2 intron variant c.-15994T (rs7699188) were associated with an increased risk of severe cytolysis, whereas ABCC2 c.3563A allele had a protective effect, as well as ABCB1 variants rs2032582 and rs1128503 (p-value &lt, 0.05). Furthermore, CYP3A5*1 rs776746 (c.6986A &gt, G) increased the risk of severe overall hepatotoxicity (p = 0.012, odds ratio (OR) = 5.75), suggesting the implication of metabolites in the hepatotoxicity. However, these results did not remain significant after multiple analysis correction. These findings need to be validated on larger cohorts of patients, with mechanistic studies potentially being able to validate the functional consequences of these variants.
Published: 2020

24. Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study

Author: Aurélie François, Lina Bezdetnaya, Ilya Yakavets, Alice Benoit, Jean-Louis Merlin, Guillaume Vogin, 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, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Centre François Baclesse, Centre National de Radiothérapie du Grand Duché du Luxembourg
Subjects: Cellular homeostasis, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Models, Biological, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Fibrosis, Spheroids, Cellular, medicine, Tumor Cells, Cultured, Humans, Cancer models, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, Multidisciplinary, Radiotherapy, Chemistry, Spheroid, medicine.disease, Coculture Techniques, 3. Good health, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, MCF-7 Cells, Immunohistochemistry, Transforming growth factor
Abstract: Radiation-induced fibrosis (RIF) is the main late radiation toxicity in breast cancer patients. Most of the current 3D in vitro breast cancer models are composed by cancer cells only and are unable to reproduce the complex cellular homeostasis within the tumor microenvironment to study RIF mechanisms. In order to account complex cellular interactions within the tumor microenvironment, an advanced 3D spheroid model, consisting of the luminal breast cancer MCF-7 cells and MRC-5 fibroblasts, was developed. The spheroids were generated using the liquid overlay technique in culture media into 96-well plates previously coated with 1% agarose (m/v, in water). In total, 21 experimental setups were tested during the optimization of the model. The generated spheroids were characterized using fluorescence imaging, immunohistology and immunohistochemistry. The expression of ECM components was confirmed in co-culture spheroids. Using α-SMA staining, we confirmed the differentiation of healthy fibroblasts into myofibroblasts upon the co-culturing with cancer cells. The induction of fibrosis was studied in spheroids treated 24 h with 10 ng/mL TGF-β and/or 2 Gy irradiation. Overall, the developed advanced 3D stroma-rich in vitro model of breast cancer provides a possibility to study fibrosis mechanisms taking into account 3D arrangement of the complex tumor microenvironment.
Published: 2020

25. Management of cN0 low‐grade mucoepidermoid carcinomas of salivary glands: Prospective multicentre study of 152 cases of the French Network of Rare Head and Neck Tumors (REFCOR)

Author: Francois Mouawad, Béatrix Barry, Philippe Herman, Nicolas Fakhry, Bertrand Baujat, Ludovic de Gabory, Sébastien Vergez, Vianney Bastit, Juliette Thariat, Laurie Saloner Dahan, Olivier Mauvais, Gilles Poissonnet, J.-C. Merol, Laurent Gilain, Thomas Radulesco, Justin Michel, Renaud Garrel, Caroline Even, Emmanuelle Uro-Coste, Dominique Chevalier, C.-A. Bach, Roch Giorgi, C.-A. Righini, Olivier Malard, Xavier Dufour, Valérie Costes-Martineau, Patrick Dessi, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), CHU Marseille, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de la Face et du Cou [Nice], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chirurgie ORL et cervico-faciale [Centre François Baclesse], 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), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), dormoy, valerian, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Mucoepidermoid carcinoma, medicine, Humans, Prospective Studies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030223 otorhinolaryngology, ComputingMilieux_MISCELLANEOUS, Aged, Neoplasm Staging, Aged, 80 and over, business.industry, Head and neck tumors, Cancer, Middle Aged, medicine.disease, Salivary Gland Neoplasms, Combined Modality Therapy, 3. Good health, Parotid gland, Survival Rate, medicine.anatomical_structure, Otorhinolaryngology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Lymph Node Excision, Carcinoma, Mucoepidermoid, Female, Radiology, France, Neoplasm Grading, business
Abstract: International audience
Published: 2020

26. Radiothérapie stéréotaxique des tumeurs primitives extracrâniennes

Author: N. Barry de Longchamps, X. Mirabel, P. Giraud, A. Dohan, Delphine Lerouge, I. Latorzeff, P. Mordant, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Clinique Pasteur [Toulouse], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interventional radiology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, Stereotactic radiotherapy, Late toxicity, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Oncology, Tolerability, 030220 oncology & carcinogenesis, Medicine, Radiology, Nuclear Medicine and imaging, Fundamental change, Radiology, business, Lung cancer, ComputingMilieux_MISCELLANEOUS
Abstract: Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.
Published: 2020

27. Radiation therapy on primary tumour of synchronous metastatic head and neck squamous cell carcinomas

Author: Yungan Tao, X. Sun, Florian Clatot, É. Tang, Anna Rose Johnson, T.V.F. Nguyen, A. Rambeau, Juliette Thariat, Département de radiothérapie, 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 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 Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Radiothérapie [Centre François Baclesse], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and ARCHADE (Advanced Resource Centre for HADrontherapy in Europe)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Context (language use), Disease, Systemic therapy, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Neoplasm Metastasis, business.industry, Squamous Cell Carcinoma of Head and Neck, Retrospective cohort study, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Radiation therapy, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Radiology, business, Literature survey, Algorithms
Abstract: Purpose Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. Material and methods We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. Results Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. Conclusion Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.
Published: 2020

28. Situation professionnelle à long terme après un cancer : étude réalisée à partir de registres de population

Author: Michel Velten, Idlir Licaj, Florence Joly, Julien Rod, Mariette Mercier, Delphine Klein, François Gernier, Akila Saim, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de recherche clinique [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de Pédiatrie Médicale [Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 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), 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 [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CCSD, Accord Elsevier, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, Les Hôpitaux Universitaires de Strasbourg (HUS), EA3430, Registre des cancers du Bas-Rhin, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and 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)
Subjects: 0301 basic medicine, Gynecology, Quality of life, Cancer Research, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Registry-based study, Hematology, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Employment status, 030220 oncology & carcinogenesis, medicine, Radiology, Nuclear Medicine and imaging, business, Cancer
Abstract: Resume Introduction Peu d’etudes ont explore la situation professionnelle a long terme apres un cancer. Notre objectif etait d’etudier le statut d’emploi des patients en longue remission d’un cancer a cinq, dix ou quinze ans apres diagnostic et de le comparer a celui des sujets sans antecedent de cancer. Methodes A partir des donnees d’une etude transversale, realisee aupres de patients en longue remission d’un cancer du sein, du col uterin ou du cancer colorectal tires au sort a partir de trois registres des cancers en France et compares a des sujets sans antecedent de cancer tires au sort sur liste electorale, nous avons selectionne les participants actifs âges de moins de 60 ans au moment de l’enquete. Nous avons etudie le statut d’emploi des cas et des temoins et les facteurs associes a ce statut. Resultats Cinq, dix ou quinze ans apres le diagnostic, nous n’observions pas de difference significative concernant le statut d’emploi entre les cas et les temoins. Parmi les cas, 17 % avaient perdu leur emploi. Etaient associes a une perte d’emploi: un âge plus avance, des revenus plus faibles, un niveau d’education plus bas, un contrat de travail de courte duree, la presence de comorbidites, de fatigue et une qualite de vie plus degradee. Discussion Bien que le statut d’emploi des cas etait comparable a la population temoin, il faut intensifier les efforts pour faciliter le retour a l’emploi des patients en longue remission d’un cancer.
Published: 2020

29. Dix ans de progrès en chirurgie des tumeurs de la tête et du cou, quel impact sur la radiothérapie postopératoire ?

Author: Jennifer Le Guevelou, Emmanuel Micault, Corinne Jeanne, Vincent Patron, Vianney Bastit, Maxime Humbert, Audrey Lasne-Cardon, Thomas Leleu, Bernard Gery, C. Florescu, Amaury Dugas, Emmanuel Babin, Juliette Thariat, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: 0301 basic medicine, Cancer Research, Reconstructive surgery, medicine.medical_specialty, Bone flap, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Postoperative radiotherapy, Minimal invasive surgery, 03 medical and health sciences, 0302 clinical medicine, medicine, Radiology, Nuclear Medicine and imaging, business.industry, Open surgery, Soft tissue, Hematology, General Medicine, 3. Good health, Surgical morbidity, Surgery, Radiation therapy, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business
Abstract: Minimal invasive surgery and reconstructive surgery tend to become the standard in France in the management of head and neck tumors. The use of endoscopic approaches (through endoscopic endonasal/transoral approaches±robot-assisted) instead of open surgery and the use of reconstructive surgery using autologous (flaps) or heterologous materials aim to reduce surgical morbidity by making-up for the loss of substance to restore the function. The impact of these substantial changes in surgical techniques has not been assessed with respect to postoperative radiotherapy practice. Endoscopic endonasal approaches result, however, in piecemeal resection, which, along the analysis of resection margins (a key prognostic factor), make the interpretation of the quality of resection more complex for radiation oncologists. The definition of tumour sub-volumes to be irradiated and doses to these sub-volumes then requires accurate histosurgical mapping and close multidisciplinary consultation between surgeons, pathologists, radiologists and radiation oncologists. Similarly, the increasing use of various types of flaps (of soft tissue or bone flaps), adapted to the patient and tumor anatomy, is associated with substantial modifications to the operating bed. The delineation of tumour volumes in postoperative radiotherapy is made more complex. Tremendous multidisciplinary efforts should now be initiated to fully take advantage of surgical advances and to further optimize the therapeutic index by making radiotherapy also less toxic, i.e. "mini-morbid".
Published: 2020

30. La qualité de vie dans les essais thérapeutiques d’inhibiteurs de checkpoints immunitaires

Author: Florence Joly, Elodie Coquan, Service de recherche clinique [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Immune checkpoint inhibitors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, In patient, Potential impact, Chemotherapy, business.industry, Hematology, General Medicine, humanities, 3. Good health, [SDV] Life Sciences [q-bio], Measurement scales, 030104 developmental biology, 030220 oncology & carcinogenesis, business, Adjuvant, Prolonged treatment
Abstract: Immune checkpoint inhibitors (ICI) have revolutionized oncological management in several tumor types, allowing prolonged tumoral responses. Thus, they are administered over long periods of time and can give specific autoimmune adverse reactions that may have a potential impact on quality of life (QoL). Most of phase III trials with ICI have included an assessment of QoL. In metastatic setting, in comparison with chemotherapy or targeted therapies, they indicate an absence of degradation of the QoL scores or even an improvement of these scores. In adjuvant setting, the deterioration of QoL scores is not clinically significant, regardless of the ICI used. In addition, there is no impairment of quality of life in patients with prolonged treatment duration. However, the measurement of QoL under ICI remains a challenge because of the specificities of these treatments and adapted measurement scales are being developed to improve the assessment of the impact of these treatments on patients' QoL.
Published: 2020

31. Mesure de la dose délivrée hors champ à l’utérus lors d’un traitement ORL par protons

Author: C. Villagrasa, Anthony Vela, A. Isambert, Juliette Thariat, J. Le Guevelou, François Trompier, Joel Herault, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), PSE-SANTE/SDOS/LDRI, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), and PSE-SANTE/SER/UEM
Subjects: Dosimeter, business.industry, Equivalent dose, [SDV]Life Sciences [q-bio], Uterus, Proportional counter, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, medicine, Dosimetry, Radiology, Nuclear Medicine and imaging, Radiation protection, Pencil-beam scanning, Nuclear medicine, business, Proton therapy
Abstract: International audience; La décision d’irradiation en cours de grossesse repose sur un compromis bénéfice risque de deux ordres :le risque maternel et le risque fœtal. L’objectif de ce travail concernait le risque fœtal et la procédure demesure de dose à l’utérus en protonthérapie par faisceau pulsé. L’exposition fœtale au cours du traite-ment est liée à deux sources : la phase de traitement, et la phase de repositionnement. Sur un fantômeanthropomorphe de type Alderson-Rando (170 cm, 74 kg) en position de traitement, un détecteur detype « Compteur Proportionnel Equivalent-Tissu » (CPET), adapté à l’analyse des champs de rayonne-ments complexes (neutroniques et photoniques) a été utilisé pour la phase de traitement. Un radiamètrede type AT1123 a été utilisé pour la mesure des photons engendrés par les rayonnements X. Une dosimé-trie in vivo a été proposée via des dosimètres radio-photo-luminescents placés à la thyroïde en utilisantun facteur de proportionnalité permettant une vérification de la dose fœtale de manière quotidienne. Laphase de traitement engendre des doses à l’utérus plus élevées que pour la phase de positionnement,néanmoins celles-ci restent très faibles. La dose équivalente au niveau de l’utérus pour l’ensemble dutraitement est de 840 Sv. Il a pu être mis au point une méthodologie de mesure de la dose hors champen faisceau pulsé de protonthérapie ORL. La dose fœtale au premier trimestre était bien inférieure aux100 mGy déterminés par la Commission Internationale de Protection Radiologique
Published: 2020

32. Intérêt de la trimodalité TEP/TDM/IRM pour la radiothérapie

Author: Romain Modzelewski, M. Levitchi, Isabelle Gardin, Pierre Decazes, Agathe Edet-Sanson, D. Defta, L. Lebret, D. Gensanne, P. Gouel, Pierre Vera, P. Hinault, F. Callonnec, O. Veresezan, Sébastien Thureau, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Radiological and Ultrasound Technology, business.industry, 030220 oncology & carcinogenesis, [SDV]Life Sciences [q-bio], Biophysics, Medicine, Radiology, Nuclear Medicine and imaging, business, 030218 nuclear medicine & medical imaging
Published: 2020

33. Intérêt de l’imagerie fonctionnelle pour la radiothérapie

Author: Pierre Decazes, Isabelle Gardin, D. Gensanne, Romain Modzelewski, Sébastien Hapdey, Pierre Vera, P. Gouel, Bernard Dubray, Sébastien Thureau, Imagerie médicale - Médecine nucléaire [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Radiological and Ultrasound Technology, [SDV]Life Sciences [q-bio], Biophysics, Radiology, Nuclear Medicine and imaging, 030218 nuclear medicine & medical imaging
Abstract: Medecine Nucleaire - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le dimanche 16 fevrier 2020
Published: 2020

34. Increased risk of central nervous system tumours with carbamate insecticide use in the prospective cohort AGRICAN

Author: Séverine Tual, Mathilde Bureau, Xavier Schwall, Anne Gruber, Camille Pouchieu, Virginie Rondeau, Béatrix Béziat, Camille Carles, Mathilde Boulanger, Clément Piel, Isabelle Baldi, Lucile Migault, Yannick Lecluse, Pierre Lebailly, Bodescot, Myriam, Cancer environnement (EPICENE ), 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)-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), 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), CHU Bordeaux [Bordeaux], Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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, and This work was supported by Ligue Contre le Cancer (Nationale and Comités du Calvados, de l’Orne, de la Manche, du Maine-et-Loire et de Paris), Mutualité Sociale Agricole (caisse centrale et caisses des Alpes du Nord, de l’Alsace, de Bourgogne-Franche Comté, des Côtes Normandes, de Gironde, de Loire Atlantique–Vendée, de Midi Pyrénées Nord, de la Picardie), Fondation de France (Mr Edouard Serres), Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (within the call for projects 2005, 2006 and 2010 of the programme «Environnement Santé Travail » of ANSES, with funding from l’ONEMA in support of the Ecophyto 2018 plan), Institut National du Cancer [InCA 8422], Association pour la Recherche sur le Cancer [ARC 02–010], Institut National de Médecine Agricole, Centre François Baclesse and Ministère de l’Enseignement Supérieur et de la Recherche.
Subjects: Male, 0301 basic medicine, Oncology, Epidemiology, medicine.medical_treatment, carbamates, Central Nervous System Neoplasms, chemistry.chemical_compound, 0302 clinical medicine, cohort studies, Medicine, risk factors, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Thiofanox, agriculture, 2. Zero hunger, Hazard ratio, General Medicine, Middle Aged, 3. Good health, Cohort, Female, France, insecticides, Cohort study, Adult, medicine.medical_specialty, Carbamate, CNS tumours, [SDV.CAN]Life Sciences [q-bio]/Cancer, farmers, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carbaryl, Humans, cancer, Aged, Proportional Hazards Models, business.industry, Proportional hazards model, occupational exposure, pesticides, Agricultural Workers' Diseases, 030104 developmental biology, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Background:Pesticide exposures are suspected to be implicated in the excess of central nervous system (CNS) tumours observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate insecticides, used on a wide range of crops, have shown evidence of carcinogenicity in some experimental studies. In the cohort AGRICAN (AGRIculture & CANcer), we assessed the associations between potential exposures to carbamate insecticides and the incidence of CNS tumours, overall and by histological subtype.Methods:AGRICAN enrolled 181 842 participants involved in agriculture. Incident CNS tumours were identified by linkage with cancer registries from enrolment (2005-07) until 2013. Carbamate exposure was assessed by combining information on lifetime periods of pesticide use on crop or livestock and the French crop-exposure matrix PESTIMAT, individually for each of the 19 carbamate insecticides registered in France since 1950. Associations were estimated using proportional hazards models with age as the underlying time scale, adjusting for gender, educational level and smoking.Results:During a 6.9-year average follow-up, 381 incident cases of CNS tumours occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumours with overall exposure to carbamate insecticides and linear trends with duration of use of each carbamate. Considering tumour subtypes, hazard ratios for gliomas ranged from 1.18 for thiofanox to 4.60 for formetanate, and for meningiomas from 1.51 for carbaryl to 3.67 for thiofanox.Conclusions:Findings reinforce carcinogenicity evidence for already suspected active ingredients and draw attention to additional active ingredients, notably used on fruit trees, vineyards, potatoes and beets.
Published: 2019

35. Occupational exposure to pesticides and multiple myeloma in the AGRICAN cohort

Author: Alain Monnereau, Pierre Lebailly, Séverine Tual, Clémentine Lemarchand, Mathilde Boulanger, Anne-Valérie Guizard, Noémie Levêque-Morlais, Stéphanie Perrier, Patrick Karuranga, Camille Pouchieu, AGRICAN-Group, Amandine Busson, Isabelle Baldi, Romain Pons, Marine Renier, Elisabeth Marcotullio, Clément Piel, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Cancer environnement (EPICENE ), 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)-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), Caisse Centrale de la Mutualité Sociale Agricole (CCMSA), Registre Général des Tumeurs du Calvados, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Institut Bergonié [Bordeaux], UNICANCER, CHU Bordeaux [Bordeaux], This work was supported by the Ligue Contre le Cancer (Nationale and Comités du Calvados, de l’Héraut, des Landes, de la Loire, du Maine et Loire, de la Manche, de l’Orne, de Paris et des Pyrénées Atlantiques), the Mutualité Sociale Agricole (caisse centrale et caisses des Alpes du Nord, de l’Alsace, de Bourgogne, des Côtes Normandes, de Franche Comté, de Gironde, de Loire Atlantique–Vendée, de Midi Pyrénées Nord, de la Picardie), the Fondation de France (Mr Edouard Serres), the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES) (within the call for projects 2005, 2006 and 2010 of the program «Environnement Santé Travail» of ANSES, with funding from l’Office national de l’eau et des milieux aquatiques in support of the Ecophyto 2018 plan), the Institut National du Cancer [Grant No. InCA 8422], the Association pour la Recherche sur le Cancer [Grant No. ARC 02–010], the Institut National de Médecine Agricole, the Centre François Baclesse, Ministère de l’Enseignement Supérieur et de la Recherche., AGRICAN-Group, and Bodescot, Myriam
Subjects: Male, Cancer Research, medicine.medical_specialty, Insecticides, [SDV.SA.STA] Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cohort Studies, Toxicology, Crop, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Multiple myeloma, [SDV.SA.STA]Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, Epidemiology, Animals, Humans, Medicine, Horses, Prospective Studies, 030212 general & internal medicine, Pesticides, Aged, Proportional Hazards Models, Aged, 80 and over, 2. Zero hunger, Farmers, Corn, business.industry, Proportional hazards model, Hazard ratio, Farming, Cohort, food and beverages, Agriculture, Middle Aged, Pesticide, Occupational exposure, Confidence interval, 3. Good health, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; PURPOSE:Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure.METHODS:Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI).RESULTS:MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend
Published: 2019

36. Molecular characterization of Equine Infectious Anemia Viruses using targeted sequence enrichment and next generation sequencing

Author: Alexandre Deshiere, Aymeric Hans, Nicolas Berthet, F. Lecouturier, D. Gaudaire, Physiopathologie et épidémiologie des maladies équines (PhEED), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP), Alexandre Deshiere and 'CENTAURE project' was supported by a grant awarded by the Regional Council of Normandy and the French Ministry of Higher Education, within the framework of CPER 2015–2020 and FEDER/FSE 2014–2020. Study's financial support was obtained from the « Institut Français du cheval et de l’équitation (IFCE) », the European Reference Laboratory for Equine Diseases other than African Horse Sickness, Anses's own institutional resources. Anses-Laboratory for animal health in Normandy is a member of the GIS Centaure equine research., The authors would like to thank the high-throughput sequencing platform SeSAME (Sequencing for Health, Agronomy, the Sea and the Environment) of the Centre François Baclesse for the access to core facilities and advice with sample processing and analysis. We also thank official veterinary services for conducting the epidemiological investigations and tissue collection on infected horses. We are also grateful to Gaël Amelot for his technical assistance on the project as well as Arnaud Prehu, Sabrina Hauvel and Pascal Saussey for administrative support, ANSES, Laboratoire de Santé Animale - site de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Institut Pasteur [Paris]
Subjects: Mutation rate, animal diseases, viruses, [SDV]Life Sciences [q-bio], Horse, Genome, MESH: Proviruses, Retrovirus, Proviruses, MESH: Animals, MESH: Genetic Variation, Targeted enrichment system, MESH: Phylogeny, MESH: High-Throughput Nucleotide Sequencing, Phylogeny, 0303 health sciences, biology, 030302 biochemistry & molecular biology, virus diseases, High-Throughput Nucleotide Sequencing, 3. Good health, MESH: Equine Infectious Anemia, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Equine Infectious Anemia, NGS, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Infectious Anemia Virus, Equine, France, MESH: Whole Genome Sequencing, MESH: Asymptomatic Diseases, Virus, DNA sequencing, Equine infectious anemia, 03 medical and health sciences, Virology, Animals, Genetic variability, Horses, MESH: Horses, 030304 developmental biology, Whole Genome Sequencing, Genetic Variation, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, MESH: France, genomic DNA, Asymptomatic Diseases, Infectious Anemia Virus, Equine
Abstract: International audience; Equine infectious anemia virus (EIAV) is responsible of acute disease episodes characterized by fever, anemia, thrombocytopenia and anorexia in equids. The high mutation rate in EIAV genome limited the number of full genome sequences availability. In the present study, we used the SureSelect target enrichment system with Illumina Next Generation Sequencing to characterize the proviral DNA of Equine Infectious Anemia Virus (EIAV) from asymptomatic horses. This approach allows a direct sequencing of the EIAV whole genome without cloning or amplification steps and we could obtain for the first time the complete genomic DNA sequences of French EIAV strains. We analyzed their phylogenetic relationship and genetic variability by comparison with 17 whole EIAV genome sequences from different parts of the world. The results obtained provide new insights into the molecular detection of EIAV and genetic diversity of European viral strains.
Published: 2019

37. 18F-FDG PET/CT heterogeneity quantification through textural features in the era of harmonisation programs: a focus on lung cancer

Author: Nicolas Aide, Pascal Do, Brice Lavigne, Jeannick Madelaine, Mathieu Hatt, Charline Lasnon, Mohamed Majdoub, Dimitris Visvikis, Biologie et Thérapies Innovantes des Cancers Localement Agressifs ( BioTICLA ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Caen Normandie ( UNICAEN ), Nuclear Medicine Department, University Hospital, Caen, Laboratoire de Traitement de l'Information Medicale ( LaTIM ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Mines-Télécom [Paris], Centre François Baclesse, Pulmonology department, University Hospital, Caen, Biologie et Thérapies Innovantes des Cancers Localement Agressifs (BioTICLA), 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-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de médecine nucléaire [CHU Caen], 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), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de pneumologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hatt, Mathieu, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Point spread function, Tumour heterogeneity, Context (language use), [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Iterative reconstruction, EARL accreditation program, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Discriminative model, Quantification, Histogram, medicine, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Harmonisation, business.industry, Pattern recognition, General Medicine, FDG PET/CT, 3. Good health, Gaussian filter, Positron emission tomography, 030220 oncology & carcinogenesis, symbols, Artificial intelligence, Heterogeneity, Lung cancer, business, Nuclear medicine
Abstract: International audience; PURPOSE:Quantification of tumour heterogeneity in PET images has recently gained interest, but has been shown to be dependent on image reconstruction. This study aimed to evaluate the impact of the EANM/EARL accreditation program on selected 18F-FDG heterogeneity metrics.METHODS:To carry out our study, we prospectively analysed 71 tumours in 60 biopsy-proven lung cancer patient acquisitions reconstructed with unfiltered point spread function (PSF) positron emission tomography (PET) images (optimised for diagnostic purposes), PSF-reconstructed images with a 7-mm Gaussian filter (PSF7) chosen to meet European Association of Nuclear Medicine (EANM) 1.0 harmonising standards, and EANM Research Ltd. (EARL)-compliant ordered subset expectation maximisation (OSEM) images. Delineation was performed with fuzzy locally adaptive Bayesian (FLAB) algorithm on PSF images and reported on PSF7 and OSEM ones, and with a 50 % standardised uptake values (SUV)max threshold (SUVmax50%) applied independently to each image. Robust and repeatable heterogeneity metrics including 1st-order [area under the curve of the cumulative histogram (CHAUC)], 2nd-order (entropy, correlation, and dissimilarity), and 3rd-order [high-intensity larger area emphasis (HILAE) and zone percentage (ZP)] textural features (TF) were statistically compared.RESULTS:Volumes obtained with SUVmax50% were significantly smaller than FLAB-derived ones, and were significantly smaller in PSF images compared to OSEM and PSF7 images. PSF-reconstructed images showed significantly higher SUVmax and SUVmean values, as well as heterogeneity for CHAUC, dissimilarity, correlation, and HILAE, and a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. Histological subtypes had no impact on TF distribution. No significant difference was observed between any of the considered metrics (SUV or heterogeneity features) that we extracted from OSEM and PSF7 reconstructions. Furthermore, the distributions of TF for OSEM and PSF7 reconstructions according to tumour volumes were similar for all ranges of volumes.CONCLUSION:PSF reconstruction with Gaussian filtering chosen to meet harmonising standards resulted in similar SUV values and heterogeneity information as compared to OSEM images, which validates its use within the harmonisation strategy context. However, unfiltered PSF-reconstructed images also showed higher heterogeneity according to some metrics, as well as a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. This suggests that, whenever available, unfiltered PSF images should also be exploited to obtain the most discriminative quantitative heterogeneity features.
Published: 2016

38. Practical contouring guidelines with an MR-based atlas of brainstem structures involved in radiation-induced nausea and vomiting

Author: Henri M. Duvernoy, Juliette Thariat, Jean-Christophe Faivre, Alexis Lacout, Julia Salleron, Michel Lefranc, Julien Welmant, Jennifer Le Guevelou, Alexandre Coutte, Sébastien Guihard, Y. Pointreau, Dominique Hasboun, A. Beddok, Jean-Baptiste Clavier, G. Janoray, Valentin Calugaru, CHU Amiens-Picardie, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Radiothérapie [Centre François Baclesse], and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: medicine.medical_specialty, Nausea, Vomiting, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Contouring, medicine.diagnostic_test, business.industry, Area postrema, Magnetic resonance imaging, Hematology, Magnetic Resonance Imaging, Pons, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Brainstem, Radiology, medicine.symptom, Radiotherapy, Conformal, business, Tomography, X-Ray Computed, Brain Stem
Abstract: Background and purpose The objective of this project was to define consensus guidelines for delineating brainstem substructures (dorsal vagal complex, including the area postrema) involved in radiation-induced nausea and vomiting (RINV). The three parts of the brainstem are rarely delineated, so this study was also an opportunity to find a consensus on this subject. Materials and methods The dorsal vagal complex (DVC) was identified on autopsy sections and endoscopic descriptions. Anatomic landmarks and boundaries were used to establish radio-anatomic correlations on CT and Magnetic Resonance Imaging (MRI). Additionally, delineation of RINV structures was performed on MRI images and reported on CT scans. Next, guidelines were provided to eight radiation oncologists for delineation guidance of these RINV-related structures on DICOM-RT images of two patients being treated for a nasopharyngeal carcinoma. Interobserver variability was computed. Results The DVC and the three parts of the brainstem were defined with a concise description of their main anatomic boundaries. The interobserver analysis showed that the DVC, the midbrain, the pons, and the medulla oblongata delineations were reproducible with KI = 0.72, 0.84, 0.94 and 0.89, respectively. The Supplemental Material section provides an atlas of the consensus guidelines projected on 1-mm MR axial slices. Conclusions This RINV-atlas was feasible and reproducible for the delineation of RINV structures on planning CT using fused MRI. It may be used to prospectively assess dose–volume relationship for RINV structures and occurrence of nausea vomiting during intracranial or head and neck irradiation.
Published: 2018

39. Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies

Author: Florence Joly, Muriel Habibian, Manish Kohli, Jean Marie Boher, Christopher Sweeney, Jorge A. Garcia, Glenn Liu, Gwenaelle Gravis, Joel Picus, Mario J. Eisenberger, Michel Soulié, David M. Jarrard, Maha Hussain, Michael A. Carducci, Karim Fizazi, Nicholas J. Vogelzang, Robert Dreicer, Stéphane Oudard, Yu-Hui Chen, Robert S. DiPaola, 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), Unité de Biostatistiques [Institut Paoli-Calmettes] (Département de la Recherche clinique et de l'Innovation), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), ECOG-ACRIN Biostatistics Center [Boston, MA, USA], Dana-Farber Cancer Institute [Boston], Carbone Cancer Center [Madison, WI, USA], University of Wisconsin-Madison, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Johns Hopkins University (JHU), Service d'oncologie médicale [CHU HEGP], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie génétique [Caen] (Centre François Baclesse), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service d'Urologie - Transplantation Rénale - Andrologie, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Virginia [Charlottesville, VA, USA], Cleveland Clinic, Comprehensive Cancer [Ann Arbor, MI, USA], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Mayo Clinic [Rochester, MN, USA], Mayo Clinic [Rochester], Nevada Cancer Research Foundation, Saint Louis University (SLU), College of Medicine [Lexington, KY, USA], University of Kentucky, 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), 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), 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), Département d'Urologie-Andrologie et Transplantation Rénale [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Kentucky (UK), and Dupuis, Christine
Subjects: Oncology, Male, medicine.medical_specialty, Urology, 030232 urology & nephrology, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Docetaxel, Metastatic castrate naive prostate cancer, Androgen deprivation therapy, Metastasis, Gonadotropin-Releasing Hormone, 03 medical and health sciences, Prostate cancer, Metastatic prostate cancer, 0302 clinical medicine, High volume, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Chemotherapy, Neoplasm Metastasis, Low volume, Aged, Randomized Controlled Trials as Topic, business.industry, Hazard ratio, Prostatic Neoplasms, Androgen Antagonists, Middle Aged, medicine.disease, Prognosis, Confidence interval, 3. Good health, Tumor Burden, Survival Rate, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Volume disease, business, Orchiectomy, medicine.drug
Abstract: International audience; BACKGROUND:Docetaxel (D) at the time of starting androgen deprivation therapy (ADT) for metastatic castrate naive prostate cancer shows a clear survival benefit for patients with high-volume (HV) disease. It is unclear whether patients with low-volume (LV) disease benefit from early D.OBJECTIVE:To define the overall survival (OS) of aggregate data of patient subgroups from the CHAARTED and GETUG-AFU15 studies, defined by metastatic burden (HV and LV) and time of metastasis occurrence (at diagnosis or after prior local treatment [PRLT]).DESIGN, SETTING, AND PARTICIPANTS:Data were accessed from two independent phase III trials of ADT alone or ADT+D-GETUG-AFU15 (N=385) and CHAARTED (N=790), with median follow-ups for survivors of 83.2 and 48.2 mo, respectively. The definition of HV and LV disease was harmonized.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary end point was OS.RESULTS AND LIMITATIONS:Meta-analysis results of the aggregate data showed significant heterogeneity in ADT+D versus ADT effect sizes between HV and LV subgroups (p=0.017), and failed to detect heterogeneity in ADT+D versus ADT effect sizes between upfront and PRLT subgroups (p=0.4). Adding D in patients with HV disease has a consistent effect in improving median OS (HV-ADT: 34.4 and 35.1 mo, HV-ADT+D: 51.2 and 39.8 mo in CHAARTED and GETUG-AFU15, respectively; pooled average hazard ratio or HR (95% confidence interval [CI]) 0.68 ([95% CI 0.56; 0.82], p
Published: 2018

40. Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study

Author: Gilles Poissonnet, Jean-Claude Merol, Esteban Brenet, Frederic Peyrade, José Santini, Maria Lesnik, Pierre Demez, Jocelyn Gal, Pierre Ransy, E. Berta, Emmanuel Babin, Alexandre Bozec, Emmanuel Chamorey, Marie-Yolande Louis, Olivier Dassonville, Karen Benezery, D. Blanchard, Dominique De Raucourt, Institut Universitaire de la Face et du Cou [Nice], Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Liege, Belgium, Département Recherche Clinique Innovation et Statistiques/Unité d'Epidémiologie et Biostatistiques (Centre Antoine Lacassagne), FNCLL, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Department of Maxillo-facial and Head and Neck Surgery, Centre François-Baclesse, Caen, Centre Hospitalier Universitaire de Reims (CHU Reims), Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Reims, Service d'ORL, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service d’Otorhino-laryngologie et de chirurgie cervicofaciale [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), Department of Otorhinolaryngology and Head and Neck Surgery, Hospital of Annecy, Centre d'étude et de recherche sur les risques et les vulnérabilités (CERREV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [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), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: Adult, Male, Quality of life, Oropharynx cancer, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Anxiety, Hospital Anxiety and Depression Scale, Surgical Flaps, 03 medical and health sciences, 0302 clinical medicine, Swallowing, Psychosocial outcomes, Surveys and Questionnaires, medicine, Humans, Prospective Studies, Voice Handicap Index, 030223 otorhinolaryngology, Prospective cohort study, Head and neck cancer, Aged, Aged, 80 and over, business.industry, Depression, Middle Aged, Plastic Surgery Procedures, medicine.disease, Prognosis, Dysphagia, humanities, 3. Good health, Survival Rate, Forearm, Oropharyngeal Neoplasms, Oncology, 030220 oncology & carcinogenesis, Physical therapy, Carcinoma, Squamous Cell, Female, Surgery, medicine.symptom, business, Follow-Up Studies
Abstract: International audience; ObjectiveTo assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction.MethodsPatients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis.ResultsA total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score ≥ 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores.ConclusionsPsychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.
Published: 2018

41. Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia

Author: Thérèse Aurran, Xavier Troussard, Bruno Cazin, Sophie de Guibert, Philippe Colombat, Florence Nguyen-Khac, Hervé Maisonneuve, Marie-Christine Béné, Roselyne Delepine, Elsa Tavernier, Véronique Leblond, Olivier Tournilhac, Florence Cymbalista, Stéphane Leprêtre, Christian Berthou, Caroline Dartigeas, Anne-Sophie Michallet, Pierre Feugier, Marie-Sarah Dilhuydy, Rémi Letestu, Eric Van Den Neste, Vincent Levy, Kamel Laribi, Jean-Pierre Vilque, Alain Delmer, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-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), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie [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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), AP HP, Clin Res Unit, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Registre des hémopathies malignes de Basse-Normandie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [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 Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Francim : Réseau français des registres des cancers, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Nutrition, croissance et cancer (U 1069) ( N2C ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie biologique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Adaptateurs de signalisation en hématologie ( ASIH ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre François Baclesse, Centre Hospitalier Universitaire de Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), 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 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Avicenne, Registre des hémopathies malignes de Basse-Normandie, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Cancer Research, medicine.medical_specialty, Cyclophosphamide, lymphoid leukemias, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Purine analogue, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Frail elderly, Chemotherapeutic approaches, immunotherapeutic approaches, [ SDV ] Life Sciences [q-bio], business.industry, Hematology, medicine.disease, Minimal residual disease, 3. Good health, Fludarabine, Oncology, 030220 oncology & carcinogenesis, Immunology, chronic lymphocytic leukemia, Rituximab, business, purine analogues, 030215 immunology, medicine.drug
Abstract: International audience; Elderly patients with chronic lymphocytic leukemia (CLL) are underrepresented in trials evaluating fludarabine, cyclophosphamide, and rituximab (FCR). We assessed four cycles of FCR with two additional rituximab doses on day 14 of cycles 1 and 2 in 194 untreated CLL patients \textgreater 65 years (median age 71.2) without del17p. Four FCR cycles were administered to 90.7% (176/194), with (n = 74) or without (n = 102) dose-delay and/or dose-reduction. A total of 50% grade 3/4 neutropenia occurred after each cycle. Only 6.2% cycles were associated with severe infection. Complete remission (CR) was achieved in 19.7%, and partial remission (PR) in 73.9% of patients. Minimal residual disease (MRD) was negative in 36.7%. Overall survival at 36 months was estimated at 87.4%. Oral FC and dose-dense rituximab is feasible and active in fit elderly CLL patients. However, myelosuppression is significant and frequent dose adaptations are required implying that these results cannot be generalized to unfit or frail elderly CLL
Published: 2016

42. Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab

Author: Dupont, Benoit, Mariotte, Delphine, Dugue, Audrey E., Clarisse, Benedicte, Grellard, Jean-Michel, Babin, Emmanuel, Chauffert, Bruno, Dakpé, Stéphanie, Moldovan, Cristian, Bouhier-Leporrier, Karine, Reimund, Jean-Marie, Di Fiore, Frederic, Zanetta, Sylvie, Mailliez, Audrey, Do, Pascal, Peytier, Annie, Galais, Marie-Pierre, Florescu, Carmen, Schott, Roland, Le Mauff, Brigitte, Gervais, Radj, Université de Montréal (UdeM), Laboratoire d'Immunologie [CHU Caen], 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 de recherche clinique [CHU Caen] (CRC), 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, Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Département d'oncologie médicale [Rouen], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Radiothérapie [Centre François Baclesse], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, [SDV]Life Sciences [q-bio], Cetuximab, Immunoglobulin E, Middle Aged, digestive system diseases, Drug Hypersensitivity, Drug Safety, Risk Factors, Humans, Female, France, Prospective Studies, neoplasms
Abstract: International audience; AIM Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels(
Published: 2016

43. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Hervé Avet-Loiseau, Laurent Garderet, Mamoun Dib, Marie-Odile Petillon, Brigitte Kolb, Jean Fontan, Pascal Lenain, Brigitte Pegourie, Murielle Roussel, Jean-Pierre Vilque, Bruno Royer, H. Jardel, Philippe Casassus, Olivier Decaux, Xavier Leleu, Carine Chaleteix, Catherine Traullé, Anne-Marie Stoppa, Pascale Cony-Makhoul, Mourad Tiab, Anne Banos, Riad Benramdane, Philippe Moreau, Philippe Rodon, Cyrille Hulin, Bruno Anglaret, Lotfi Benboubker, Claire Mathiot, Olivier Fitoussi, Thomas Dejoie, Service de Médecine Interne, CH Bretagne Atlantique, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), university hospital, University Hospital, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Hematology, Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Laboratoire d'Hématologie biologique, Institut Curie [Paris], Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CRLCC Henri Becquerel, Géographie-cités ( GC ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Hospices Civils de Lyon ( HCL ), Centre François Baclesse, INSTITUT CURIE, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut des Matériaux Jean Rouxel ( IMN ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Curie, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, and Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Bendamustine, Melphalan, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Phases of clinical research, elderly, Autologous stem-cell transplantation, Prednisone, hemic and lymphatic diseases, Internal medicine, medicine, bendamustine, Online Only Articles, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, relapse, [ SDV ] Life Sciences [q-bio], business.industry, Bortezomib, Hematology, medicine.disease, 3. Good health, Surgery, Thalidomide, multiple myeloma, business, medicine.drug
Abstract: In patients with multiple myeloma (MM) not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), the 2 following options are recommended as part of front-line treatment and approved based on data from randomized phase III trials: melphalan/prednisone/thalidomide (MPT), or
Published: 2015

44. Which factors predict proposal and uptake of psychological counselling after BRCA1/2 test result disclosure?

Author: Maheu, Christine, Bouhnik, Anne-Deborah, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Stoppa-Lyonnet, Dominique, Lasset, Christine, Berthet, Pascaline, Fricker, Jean-Pierre, Caron, Olivier, Luporsi, Elizabeth, Gladieff, Laurence, Julian-Reynier, Claire, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Service d'Epidémiologie Clinique et d'Information Médicale (Oncogénétique Clinique), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Service de Génétique Oncologique, Institut Curie [Paris], Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Santé publique - Oncogénétique [Lyon] (Centre Léon Bérard), Centre Léon Bérard [Lyon]-UNICANCER - Centre Léon Bérard Lyon (Rhône), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), Oncogénétique / Prévention / Dépistage [Strasbourg] (Centre Paul Strauss), Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'oncogénétique [Vandoeuvre-Lès-Nancy] (Institut de Cancérologie de Lorraine - CLCC Alexis Vautrin), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), This study was supported financially by the Institut National du Cancer RPT08011AAA, the SIRIC (grant INCA-DGOS-Inserm 6038) and the GENEPSO cohort, by ‘La Ligue Nationale Contre le Cancer’., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lissalde, Claire, Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'oncologie génétique [Caen] (Centre François Baclesse), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Département d'Oncologie Médicale [CHU Toulouse] (IUCT Oncopole - Institut Universitaire du Cancer), Centre hospitalier universitaire de Toulouse - CHU Toulouse-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Counseling, Heterozygote, Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Truth Disclosure, genetic testing, Cohort Studies, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, BRCA1/2, Odds Ratio, Humans, Genetic Predisposition to Disease, Prospective Studies, Referral and Consultation, Ovarian Neoplasms, Depression, HBOC, Social Support, Middle Aged, Logistic Models, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, psychologist services, Multivariate Analysis, Educational Status, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Stress, Psychological
Abstract: International audience; OBJECTIVE:The aim of this study is to prospectively determine the factors contributing to whether unaffected women from BRCA1/2 families reported that clinicians proposed psychological consultations and that they had attended these consultations during the genetic testing process.METHODS:A prospective study was performed on a national cohort, using self-administered questionnaires to determine the rates of proposal and use of psychological services at the time of BRCA1/2 test result disclosure (N = 533) and during the first year after disclosure (N = 478) among unaffected French women from BRCA1/2 families who had undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out using logistic regression models fitted using generalized estimation equations, with the genetic testing centre as the clustering variable.RESULTS:At the time of BRCA1/2 test result disclosure, a psychological consultation was proposed by cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N = 301), respectively (p
Published: 2014

45. Détermination automatique des paramètres du faisceau d'électrons primaires dans les simulations Monte Carlo d'accélérateurs linéaires en radiothérapie

Author: Lazaro, Delphine, Barat, Eric, Dautremer, Thomas, Montagu, Thierry, Chabert, Isabelle, Guérin, L., Batalla, Alain, Laboratoire Modélisation et Simulation de Systèmes (LM2S), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: linear accelarator, dosimetry, irradiation beam, electrons, treatment planification, simulation, modelling, particle transport, radioactivity, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], cancer, linac, ionizing radiation, Monte Carlo, radiotherapy
Abstract: National audience; En radiothérapie, la maîtrise de la dose délivrée lors d'un traitement est cruciale pour assurer la réussite de celui-ci. Grâce à la méthode de Monte Carlo (MC), une précision de l'ordre de 2-3% sur le calcul de dose lors de la planification du traitement est possible, à condition que le modèle MC de l'accélérateur linéaire (linac) reproduise fidèlement les caractéristiques physiques du faisceau d'irradiation. Pour cela, les paramètres décrivant les distributions spatiale et énergétique du faisceau primaire d'électrons doivent être réglés finement. La détermination de ces paramètres s'effectue généralement par essai/erreur jusqu'à reproduire au mieux les mesures, ce qui peut s'avérer fastidieux et chronophage, et ne garantit pas que les paramètres optimaux ont été retenus. Nous présentons ici une nouvelle méthode de détermination automatique des paramètres du faisceau primaire d'électrons.
Published: 2014

46. Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA

Author: Alain Monnereau, Yann Guillermin, Ghandi Damaj, T. Marchand, Xavier Troussard, Delphine Rossille, Gilles Salles, Pascal Godmer, Florence Broussais-Guillaumot, S. Le Gouill, Richard Lemal, Marc Maynadié, Catherine Thieblemont, Thierry Lamy, Adrien Trebouet, Emmanuel Gyan, Christophe Fruchart, Roch Houot, Hélène Monjanel, P. Feugier, Microenvironnement et cancer ( MiCa ), 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 ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie, CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I ( UdA ), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Tours, CIC - Tours, CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier de Bretagne Atlantique, Centre François Baclesse, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Département d'oncologie médicale, Institut Bergonié - CRLCC Bordeaux, CHU Caen, Pôle Biologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), 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, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Bergonié [Bordeaux], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Martin, Clémence, 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Male, medicine.medical_specialty, Palliative care, Survival, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Hypoalbuminemia, education, Serum Albumin, 030304 developmental biology, Cause of death, Retrospective Studies, Aged, 80 and over, 0303 health sciences, education.field_of_study, palliative care, business.industry, Incidence (epidemiology), Incidence, Lymphoma, Non-Hodgkin, Hematology, medicine.disease, Prognosis, Comorbidity, 3. Good health, Lymphoma, Surgery, aged 80 and over, comorbidity, Oncology, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract: International audience; BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0-92 months) for the 227 patients with non-Hodgkin Lymphoma (NHL), with a significant difference between aggressive and indolent NHL (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL patients for whom detailed characteristics were available. Among these patients, 63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was reported as the main cause of death (40%). Treatment administration was associated with improved OS in patients with aggressive (P < 0.001) but not indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia appeared as a strong and independent negative prognostic factor. CONCLUSIONS: The median OS is short in 90+ patients diagnosed with lymphoma but some patients experience prolonged survival. Lymphoma represents the main cause of death in these patients. Treatment may improve survival of selected patients with aggressive but not indolent NHL. Management of these patients may be guided by prognostic factors identified in this study, notably serum albumin.
Published: 2013

47. Rapid and soft formulation of folate-functionalized nanoparticles for the targeted delivery of tripentone in ovarian carcinoma

Author: Sylvain Rault, Laurent Poulain, Ludovic Carduner, Pascal Gauduchon, Emilie Brotin, Aurélie Malzert-Fréon, Franck Carreiras, Florence Giffard, Edwige Abeilard, Julie Tomasina, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Calvados Cancer Registry, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre François Baclesse, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), and Lesnard, Aurélien
Subjects: [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Chemistry, Pharmaceutical, Pharmaceutical Science, Nanoparticle, Endocytosis Pathway, Antineoplastic Agents, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Flow cytometry, Polyethylene Glycols, Excipients, 03 medical and health sciences, Drug Delivery Systems, Folic Acid, Ovarian carcinoma, Cell Line, Tumor, medicine, Zeta potential, Humans, Particle Size, Cytotoxicity, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, Drug Carriers, medicine.diagnostic_test, Chemistry, Carcinoma, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, 021001 nanoscience & nanotechnology, Lipids, In vitro, Biochemistry, Solubility, Nanoparticles, Female, Nanocarriers, 0210 nano-technology
Abstract: We report the development of folate-functionalized nanoparticles able to target folate receptors, and to deliver a poorly water soluble cytotoxic agent, a tripentone, in ovarian carcinoma. The stability under incubation of lipid nanoparticles formulated by a low-energy phase inversion temperature method was investigated. Thanks to the presence of Labrasol ® , a macrogolglyceride into the composition of the nanocarriers, the conjugation of different quantities of a folate derivate (folic acid-polyethylene glycol 2000 -distearylphosphatidylethanolamine) to nanoparticles was possible by a rapid, soft, very simple post-insertion process. As determined by dynamic light scattering, nanoparticles present a monodisperse diameter of about 100 nm, a spherical shape as attested by transmission electron micrographs, a weakly negative surface zeta potential, and are able to encapsulate the tripentone MR22388. The presence of folate receptors on SKOV3 human ovarian cancer cells was identified by fluorescent immunocytochemistry. Cellular uptake studies assessed by flow cytometry indicated that these nanoparticles reached the SKOV3 cells rapidly, and were internalized by a folate-receptor mediated endocytosis pathway. Moreover, nanoparticles allowed the rapid delivery of the antitumor agent tripentone into cells as shown in vitro by real-time cellular activity assay. Such folate-lipid nanoparticles are a potential carrier for targeted delivery of poorly water soluble compounds into ovarian carcinoma.
Published: 2013

48. Dual-phase 99mTc sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience

Author: Renaud Ciappuccini, Nicolas Aide, Julia Morera, Stéphane Bardet, Emmanuel Babin, Natacha Heutte, Jean-Pierre Rame, Pierre Pascal, Yves Reznik, Service de Médecine nucléaire et Unité Thyroïde [Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service Endocrinologie - Diabétologie [CHU Caen], 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), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse], Pôle de Recherche [CHU Caen] (Centre François Baclesse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de médecine nucléaire [CHU Caen], Centre d'étude et de recherche sur les risques et les vulnérabilités (CERREV), Normandie Université (NU)-Normandie Université (NU), Œstrogènes, reproduction, cancer (OeReCa), and Service de médecine nucléaire
Subjects: Thorax, Male, [SDV]Life Sciences [q-bio], Scintigraphy, Multimodal Imaging, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Medicine, Single institution, Aged, 80 and over, medicine.diagnostic_test, Parathyroid neoplasm, Hyperparathyroidism, General Medicine, Middle Aged, Hyperparathyroidism, Primary, Parathyroid Neoplasms, Parathyroid Hormone, 030220 oncology & carcinogenesis, Female, Radiology, Adult, Technetium Tc 99m Sestamibi, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sestamibi, Sensitivity and Specificity, Statistics, Nonparametric, 03 medical and health sciences, Humans, Radiology, Nuclear Medicine and imaging, Aged, Tomography, Emission-Computed, Single-Photon, Chi-Square Distribution, business.industry, SPECT/CT, 99mTc Sestamibi, medicine.disease, Positron-Emission Tomography, Surgery, Calcium, Radiopharmaceuticals, business, Tomography, X-Ray Computed, Primary hyperparathyroidism, Emission computed tomography, Biomarkers, Neck
Abstract: International audience; Purpose: To assess the diagnostic value of dual-phase 99mTc sestamibi scintigraphy with neck and thorax single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with primary hyperparathyroidism, and to analyze the relationships between SPECT/CT data and serum calcium or parathyroid hormone (PTH) concentrations.Materials and Methods: 99mTc sestamibi scintigraphy was performed in 94 consecutive patients. Images included early and delayed planar neck images and delayed neck and thorax SPECT/CT. Scintigraphy was scored positive or negative.Results: Fifty-nine sestamibi studies (63%) were positive. SPECT/CT demonstrated a single focus in 56 patients, in usual parathyroid sites in 80% of cases and in unusual sites in the remaining 20% (retrotracheal area, 7%; intrathyroidal, 9%; mediastinum, 4%), and double foci in 3. Serum calcium values were higher in patients with a positive scintigraphy than in those with a negative scintigraphy (2.80 vs. 2.66 mmol/L, P = 0.001) with similar figures for serum PTH values (129 vs. 107 pg/mL, P = 0.0649). In patients with a measurable parathyroid adenoma on integrated CT scan (n = 43), the greatest axial diameter of the adenoma was correlated to serum calcium (r = 0.405, P < 0.0071) or PTH concentrations (r = 0.589, P < 0.0001). Fifty-four patients underwent surgery, 45 with a positive, and 9 with a negative preoperative scintigraphy, resulting in a sensitivity of 92% (95% CI: 80-98) and a specificity of 83% (95% CI: 36-100).Conclusions: Dual-phase 99mTc sestamibi scintigraphy with SPECT/CT enables to identify a parathyroid adenoma in about two-thirds of patients with primary hyperparathyroidism and allows the surgeon to plan appropriate surgery. The likelihood of scintigraphy to be positive is affected by calcium or PTH concentrations.
Published: 2012

49. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

Author: Cox, D. G., Simard, J., Sinnett, D., Hamdi, Y., Soucy, P., Ouimet, M., Barjhoux, L., Verny-Pierre, C., McGuffog, L., Healey, S., Szabo, C., Greene, M. H., Mai, P. L., Andrulis, I. L., Thomassen, M., Gerdes, A.-M., Caligo, M. A., Friedman, E., Laitman, Y., Kaufman, B., Paluch, S. S., Borg, A., Karlsson, P., Stenmark Askmalm, M., Barbany Bustinza, G., Nathanson, K. L., Domchek, S. M., Rebbeck, T. R., Benitez, J., Hamann, U., Rookus, M. A., van den Ouweland, A. M. W., Ausems, M. G. E. M., Aalfs, C. M., van Asperen, C. J., Devilee, P., Gille, H. J. J. P., Peock, S., Frost, D., Evans, D. G., Eeles, R., Izatt, L., Adlard, J., Paterson, J., Eason, J., Godwin, A. K., Remon, M.-A., Moncoutier, V., Gauthier-Villars, M., Lasset, C., Giraud, S., Hardouin, A., Berthet, P., Sobol, H., Eisinger, F., Bressac de Paillerets, B., Caron, O., Delnatte, C., Goldgar, D., Miron, A., Ozcelik, H., Buys, S., Southey, M. C., Terry, M. B., Singer, C. F., Dressler, A.-C., Tea, M.-K., Hansen, T. V. O., Johannsson, O., Piedmonte, M., Rodriguez, G. C., Basil, J. B., Blank, S., Toland, A. E., Montagna, M., Isaacs, C., Blanco, I., Gayther, S. A., Moysich, K. B., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Niederacher, D., Sutter, C., Gadzicki, D., Fiebig, B., Caldes, T., Laframboise, R., Nevanlinna, H., Chen, X., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Couch, F. J., Wang, X., Peterlongo, P., Manoukian, S., Bernard, L., Radice, P., Easton, D. F., Chenevix-Trench, G., Antoniou, A. C., Stoppa-Lyonnet, D., Mazoyer, S., Sinilnikova, O. M., Dumont, M., Greene, M., Glendon, G., Selander, T., Weerasooriya, N., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark-Askmalm, M., Liedgren, S., Loman, N., Olsson, H., Kristoffersson, U., Soller, M., Jernstrom, H., Harbst, K., Henriksson, K., Lindblom, A., Arver, B., von Wachenfeldt, A., Liljegren, A., Barbany-Bustinza, G., Rantala, J., Melin, B., Gronberg, H., Stattin, E.-L., Emanuelsson, M., Ehrencrona, H., Torres, D., Rashid, M. U., Seidel-Renkert, A., Hogervorst, F. B. L., Verhoef, S., Verheus, M., van't Veer, L. J., van Leeuwen, F. E., Collee, M., Jager, A., Hooning, M. J., Tilanus-Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., van der Luijt, R. B., van Os, T. A., Gille, J. J. P., Waisfisz, Q., Meijers-Heijboer, H. E. J., Gomez-Garcia, E. B., van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., van der Hout, A. H., Mourits, M. J., Vasen, H. F., Cook, M., Platte, R., Miedzybrodzka, Z., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Ong, K.-r., Hoffman, J., Donaldson, A., James, M., Downing, S., Taylor, A., Murray, A., Rogers, M. T., McCann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Davidson, R., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Lalloo, F., Taylor, J., Side, L., Male, A., Berlin, C., Collier, R., Douglas, F., Claber, O., Jobson, I., Walker, L., McLeod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern-Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Cook, J., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Eccles, D., Lucassen, A., Crawford, G., McBride, D., Smalley, S., Sinilnikova, O., Leone, M., Buecher, B., Houdayer, C., Belotti, M., Tirapo, C., de Pauw, A., Bressac-de-Paillerets, B., Remenieras, A., Byrde, V., Lenoir, G., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Bourdon, V., Noguchi, T., Coulet, F., Colas, C., Soubrier, F., Coupier, I., Pujol, P., Peyrat, J.-P., Fournier, J., Revillion, F., Vennin, P., Adenis, C., Rouleau, E., Lidereau, R., Demange, L., Nogues, C., Muller, D., Fricker, J.-P., Longy, M., Sevenet, N., Toulas, C., Guimbaud, R., Gladieff, L., Feillel, V., Leroux, D., Dreyfus, H., Rebischung, C., Coron, F., Faivre, L., Prieur, F., Lebrun, M., Ferrer, S. F., Frenay, M., Venat-Bouvet, L., Mortemousque, I., Lynch, H. T., Snyder, C. L., Ejlertsen, B., Andersen, M. K., Kjaergaard, S., Senter, L., Sweet, K., O'Connor, M., Craven, C., Pharoah, P., Ramus, S., Pye, C., Harrington, P., Wozniak, E., Varon-Mateeva, R., Kast, K., Preisler-Adams, S., Deissler, H., Schonbuchner, I., Heinritz, W., Schafer, D., Aittomaki, K., Blomqvist, C., Heikkinen, T., Erkkila, R. N. I., Thorne, H., Niedermayr, E., de la Hoya, M., Perez-Segura, P., 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), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Department of Pediatrics, CHU Sainte Justine [Montréal], Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Queensland Institute of Medical Research, University of Delaware [Newark], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Clinical Genetics, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Department of Oncology, Sahlgrenska University Hospital [Gothenburg], Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Addenbrookes Hospital, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, génétique, Institut Curie [Paris], Service de Génétique Oncologique, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Consultation d'Oncogénétique, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre René Gauducheau, CRLCC René Gauducheau, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Internal Medicine, Huntsman Cancer Institute, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Faculty of Medicine, University of Iceland [Reykjavik], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Lombardi Comprehensive Cancer Center, Georgetown University, Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Heidelberg University Hospital [Heidelberg], Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Universität Regensburg (UR), Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, 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), Equipe 6, 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), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Centre, CHU Ste Justine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Génétique moléculaire, signalisation et cancer (GMSC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), 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]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Human Genetics, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Tel Aviv University (TAU), University of Pennsylvania-University of Pennsylvania, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Roswell Park Cancer Institute [Buffalo] (RPCI), Georgetown University [Washington] (GU), Universität Leipzig, 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 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 ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Génétique moléculaire, signalisation et cancer ( GMSC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon ( CRCL ), 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]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Cambridge [UK] ( CAM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), Sahlgrenska University Hospital, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Deutsches Krebsforschungszentrum ( DKFZ ), INSTITUT CURIE, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre François Baclesse, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Mount Sinai Hospital ( MSH ), Medical University of Vienna-Department of OB/GYN, Medical University of Vienna, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximilians-Universität München, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Hannover Medical School [Hannover] ( MHH ), University Regensburg, 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 ), Human genetics, and CCA - Oncogenesis
Subjects: endocrine system diseases, Electrophoretic Mobility Shift Assay, MESH : Breast Neoplasms, medicine.disease_cause, Linkage Disequilibrium, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Genes, Reporter, Risk Factors, MESH: Risk Factors, Genotype, MESH : Female, Luciferases, skin and connective tissue diseases, Genetics (clinical), MESH: Genetic Association Studies, MESH: Heterozygote, Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Genes, Reporter, MESH : Risk Factors, 3. Good health, MESH: Linkage Disequilibrium, 030220 oncology & carcinogenesis, MESH : Electrophoretic Mobility Shift Assay, Female, Breast disease, MESH : Mutation, MESH : Heterozygote, Heterozygote, MESH: Mutation, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, medicine, Humans, MESH : BRCA1 Protein, MESH : HeLa Cells, Genetic Predisposition to Disease, ddc:610, Allele, Molecular Biology, MESH : Haplotypes, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: BRCA1 Protein, MESH : Luciferases, MESH: Humans, Hereditary cancer and cancer-related syndromes [ONCOL 1], MESH: Alleles, Haplotype, MESH : Humans, MESH: Genes, Reporter, Cancer, MESH : Genetic Association Studies, MESH: Haplotypes, medicine.disease, Haplotypes, Mutation, MESH: Electrophoretic Mobility Shift Assay, MESH: HeLa Cells, Cancer research, MESH : Genetic Predisposition to Disease, MESH: Luciferases, Carcinogenesis, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms, HeLa Cells
Abstract: Item does not contain fulltext Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.
Published: 2011

50. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Author: Bertolotto-Ballotti, Corine, Lesueur, Fabienne, Giuliano, Sandy, Strub, Thomas, de Lichy, Mahaut, Bille, Karine, Dessen, Philippe, d'Hayer, Benoit, Mohamdi, Hamida, Remenieras, Audrey, Maubec, Eve, de La Fouchardière, Arnaud, Molinié, Vincent, Vabres, Pierre, Dalle, Stéphane, Poulalhon, Nicolas, Martin-Denavit, Tanguy, Thomas, Luc, Andry-Benzaquen, Pascale, Dupin, Nicolas, Boitier, Françoise, Rossi, Annick, Perrot, Jean-Luc, Labeille, Bruno, Robert, Caroline, Escudier, Bernard, Caron, Olivier, Brugières, Laurence, Saule, Simon, Gardie, Betty, Gad, Sophie, Richard, Stéphane, Couturier, Jérôme, Teh, Bin Tean, Ghiorzo, Paola, Pastorino, Lorenza, Puig, Susana, Badenas, Celia, Olsson, Hakan, Ingvar, Christian, Rouleau, Etienne, Lidereau, Rosette, Bahadoran, Philippe, Vielh, Philippe, Corda, Eve, Blanché, Hélène, Zelenika, Diana, Galan, Pilar, Renseigné, Non, Aubin, François, Bachollet, Bertrand, Becuwe, Céline, Berthet, Pascaline, Bignon, yves Jean, Bonadona, Valérie, Bonafe, Jean-Louis, Bonnet-Dupeyron, Marie-Noëlle, Cambazard, Fréderic, Chevrant-Breton, Jacqueline, Coupier, Isabelle, Dalac, Sophie, Demange, Liliane, d'Incan, Michel, Dugast, Catherine, Faivre, Laurence, Vincent-Fétita, Lynda, Gauthier-Villars, Marion, Gilbert, Brigitte, Grange, Florent, Grob, Jean-Jacques, Humbert, Philippe, Janin, Nicolas, Joly, Pascal, Kerob, Delphine, Lasset, Christine, Leroux, Dominique, Levang, Julien, Limacher, Jean-Marc, Livideanu, Cristina, Longy, Michel, Lortholary, Alain, Stoppa-Lyonnet, Dominique, Mansard, Sandrine, Mansuy, Ludovic, Marrou, Karine, Matéus, Christine, Maugard, Christine, Meyer, Nicolas, Nogues, Catherine, Souteyrand, Pierre, Venat-Bouvet, Laurence, Zattara, Hélène, Chaudru, Valérie, Lenoir, Gilbert M, Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, Bressac-de Paillerets, Brigitte, Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), AxesSim, Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), 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), Service d'anatomopathologie [Fort de France, Martinique], CHU Fort de France, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, 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), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Parallel Cooperative Multi-criteria Optimization (DOLPHIN), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Valorisation Recherche et Innovations Alimentaire (Valorial), University Hospital of St-Etienne, Department of Dermatology, 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), Département d'immunothérapie, Institut Gustave Roussy (IGR), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Immunologie des Tumeurs Humaines (U753), Laboratoire de Génétique Oncologique [Villejuif], École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, Service de Génétique Oncologique, Institut Curie, Van Andel Research Institute, Grand Rapids, Michigan, Van Andel Institute [Grand Rapids], University of Barcelona, Hospital Clinic Barcelona, Lund University [Lund], Department of Surgery, Clinical Sciences, Genetique Moleculaire des Cancers d'Origine Epitheliale, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], 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, Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Université d'Évry-Val-d'Essonne (UEVE), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditérannéen de médecine moléculaire (C3M), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, 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)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Apoptose, cancer et immunité (U848), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'anatomie pathologique, Hôpital Saint Joseph, 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), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Consultation de génétique, Département de Pédiatrie, Service de Pathologie, Institut Curie [Paris], Department of Oncology, Clinical Sciences, Department of Cancer Epidemiology, Clinical Sciences, Department of Surgery, University Hospital of Lund, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Hôpital René HUGUENIN (Saint-Cloud), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique Epidémiologique, Centre Léon Bérard [Lyon], CHU Saint-Etienne, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Polyclinique de Courlancy, Service de Dermatologie, Hôtel-Dieu, CRLCC Eugène Marquis (CRLCC), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM), Département de Génétique, CHU, Liège, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, Service d'onco-hématologie et génétique, CHU Grenoble, 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), 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), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Laboratoire de biostatistique, CHU Strasbourg, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Département de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Functional Genomics and Cancer, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7), We thank the patients and family members who participated in this study and the clinicians who identified these families, the French Familial Melanoma Study Group and the Inherited Predisposition to Kidney Cancer network. We acknowledge the contribution of the IGR Biobank for providing MELARISK samples and the CEPH Biobank for processing DNA samples. We thank L. Larue, J, Feunteun, A. Sarasin and E. Solary for critical reviews of the manuscript. We thank V. Lazar and S. Forget for coordination of the IGR's genomics and genetic platforms, N. Pata-Merci, V. Marty, S. Le Gras and A. Chabrier for their technical expertise, and M. Barrois for technical counselling. We also thank A. Boland for DNA extraction and quality control for genome-wide genotyping. This work was supported by grants from INSERM, Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to F. D., Programme Hospitalier de Recherche Clinique (PHRC 2007/AOM-07-195) to M.-F.A. and F. D., ARC NoA09/5/5003 to B.B.-d.P., ARC 4985 to C. B., Institut National du Cancer (INCa)-Canceropole Ile de France (melanoma network RS#13) to B.B.-deP., INCa-PNES rein to B. G., S.Ga. and S. R., INCa grant R08009AP to C. B., Fondation de France 2010 to R. B., INCa and Ligue National Contre le Cancer to I. D., Fond de maturation IGR and Fondation Gustave Roussy to B.B.-d.P., Societe Francaise de Dermatologie SDF2004 to R. B. and P. B., SFD2009 to B.B.-d.P., 2009 SGR 1337 from AGAUR, Generalitat de Catalunya, and FIS PS09/01393 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain to S. P. and C. B., and personal donations from C. and N. de Paillerets and M.-H.Wagner. to B.B.-d.P. B.B-d.P. holds an INSERM Research Fellowship for hospital-based scientists. Work at the Centre National de Genotypage (CNG) and Centre d'Etude du Polymorphisme Humain (CEPH) was supported in part by INCa., Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Génétique, Institut de cancérologie Gustave Roussy, Villejuif, France, Institut Gustave Roussy ( IGR ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), 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 Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), INSTITUT CURIE, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), 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 des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Centre François Baclesse, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, CRLCC Eugène Marquis ( CRLCC ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP), 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 ), 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 ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: multidisciplinary sciences, MESH : Germ-Line Mutation, SUMO protein, urologic and male genital diseases, medicine.disease_cause, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Gene Frequency, Cell Movement, MESH: Germ-Line Mutation, MESH : Cell Movement, MESH : Gene Frequency, MESH: Cell Movement, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Multidisciplinary, MESH: Sumoylation, Melanoma, MESH : Sumoylation, MESH: Genetic Predisposition to Disease, renal carcinoma, MESH: Carcinoma, Renal Cell, Microphthalmia-associated transcription factor, MESH : Microphthalmia-Associated Transcription Factor, 3. Good health, germline mutation, 030220 oncology & carcinogenesis, MESH: Microphthalmia-Associated Transcription Factor, science and technology, MESH: Melanoma, sumo, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Germline mutation, melanoma, MESH: Gene Frequency, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Neoplasm Invasiveness, Carcinoma, Renal Cell, neoplasms, Transcription factor, Germ-Line Mutation, 030304 developmental biology, Microphthalmia-Associated Transcription Factor, MESH: Humans, MESH : Humans, Sumoylation, MESH: Neoplasm Invasiveness, medicine.disease, HIF1A, cancer cells, Cancer research, MESH : Genetic Predisposition to Disease, Carcinogenesis
Abstract: International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
Published: 2011

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