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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. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Author: Mulligan, Anna Marie, Couch, Fergus J, Barrowdale, Daniel, Domchek, Susan M, Eccles, Diana, Nevanlinna, Heli, Ramus, Susan J, Robson, Mark, Sherman, Mark, Spurdle, Amanda B, Wappenschmidt, Barbara, Lee, Andrew, McGuffog, Lesley, Healey, Sue, Sinilnikova, Olga M, Janavicius, Ramunas, Hansen, Thomas vO, Nielsen, Finn C, Ejlertsen, Bent, Osorio, Ana, Muñoz-Repeto, Iván, Durán, Mercedes, Godino, Javier, Pertesi, Maroulio, Benítez, Javier, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Cattaneo, Elisa, Bonanni, Bernardo, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Ottini, Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Hamann, Ute, Verheus, Martijn, Meijers-Heijboer, Hanne EJ, Wijnen, Juul, Gómez García, Encarna B, Nelen, Marcel R, Kets, C Marleen, Seynaeve, Caroline, Tilanus-Linthorst, Madeleine MA, van der Luijt, Rob B, van Os, Theo, Rookus, Matti, Frost, Debra, Jones, J Louise, Evans, D Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Adlard, Julian, Davidson, Rosemarie, Cook, Jackie, Donaldson, Alan, Dorkins, Huw, Gregory, Helen, Eason, Jacqueline, Houghton, Catherine, Barwell, Julian, Side, Lucy E, McCann, Emma, Murray, Alex, Peock, Susan, Godwin, Andrew K, Schmutzler, Rita K, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ruehl, Ina, Arnold, Norbert, Niederacher, Dieter, Sutter, Christian, Deissler, Helmut, Gadzicki, Dorothea, Kast, Karin, Preisler-Adams, Sabine, Varon-Mateeva, Raymonda, Schoenbuchner, Ines, Fiebig, Britta, Heinritz, Wolfram, Schäfer, Dieter, Gevensleben, Heidrun, Caux-Moncoutier, Virginie, Fassy-Colcombet, Marion, Cornelis, François, Mazoyer, Sylvie, Léoné, Mélanie, Boutry-Kryza, Nadia, Hardouin, Agnès, Berthet, Pascaline, Muller, Danièle, Fricker, Jean-Pierre, Mortemousque, Isabelle, Pujol, Pascal, Coupier, Isabelle, Lebrun, Marine, Kientz, Caroline, Longy, Michel, Sevenet, Nicolas, Stoppa-Lyonnet, Dominique, Isaacs, Claudine, Caldes, Trinidad, de la Hoya, Miguel, Heikkinen, Tuomas, Aittomäki, Kristiina, Blanco, Ignacio, Lazaro, Conxi, Barkardottir, Rosa B, Soucy, Penny, Dumont, Martine, Simard, Jacques, Montagna, Marco, Tognazzo, Silvia, D'Andrea, Emma, Fox, Stephen, Yan, Max, Rebbeck, Tim, Olopade, Olufunmilayo, Weitzel, Jeffrey N, Lynch, Henry T, Ganz, Patricia A, Tomlinson, Gail E, Wang, Xianshu, Fredericksen, Zachary, Pankratz, Vernon S, Lindor, Noralane M, Szabo, Csilla, Offit, Kenneth, Sakr, Rita, Gaudet, Mia, Bhatia, Jasmine, Kauff, Noah, Singer, Christian F, Tea, Muy-Kheng, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Mai, Phuong L, Greene, Mark H, Imyanitov, Evgeny, O'Malley, Frances P, Ozcelik, Hilmi, Glendon, Gordon, Toland, Amanda E, Gerdes, Anne-Marie, Thomassen, Mads, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Soller, Maria, Henriksson, Karin, Wachenfeldt, von Anna, Arver, Brita, Stenmark-Askmalm, Marie, Karlsson, Per, Ding, Yuan Chun, Neuhausen, Susan L, Beattie, Mary, Pharoah, Paul DP, Moysich, Kirsten B, Nathanson, Katherine L, Karlan, Beth Y, Gross, Jenny, John, Esther M, Daly, Mary B, Buys, Saundra M, Southey, Melissa C, Hopper, John L, Terry, Mary Beth, Chung, Wendy, Miron, Alexander F, Goldgar, David, Chenevix-Trench, Georgia, Easton, Douglas F, Andrulis, Irene L, Antoniou, Antonis C, Breast Cancer Family Registry, EMBRACE, GEMO Study Collaborators, HEBON, kConFab Investigators, Ontario Cancer Genetics Network, SWE-BRCA, CIMBA, Pediatric Surgery, Neurology, Medical Oncology, Surgery, Clinical Genetics, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine and Pathology, Mayo Clinic, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Medicine, University of Pennsylvania [Philadelphia]-Abramson Cancer Center, Faculty of Medicine, University of Southampton-University Hospital Southampton, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Memorial Sloane Kettering Cancer Center [New York]-Weill Medical College of Cornell University [New York], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Queensland Institute of Medical Research, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Oncology, Human Genetics Group, Spanish National Cancer Research Centre-Spain and the Spanish Network on Rare Diseases, Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Instituto de investigación sanitaria de Aragón (IIS), Hospital clinico Universitario 'Lozano Blesa', Molecular Diagnostics Laboratory, National Center for Scientific Research 'Demokritos' (NCSR)-IRRP, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Fondazione Istituto FIRC di Oncologia Molecolare, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Unit of Medical Genetics, Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, Department of Genetics, Biology and Biochemistry, University of Turin, Medical Genetics Unit, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Division of Medical Oncology, Regina Elena Cancer Institute, Department of Experimental Oncology, Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia. Milan, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, Netherlands Cancer Institute, Department of Clinical Genetics, VU Medical Center, Department of Human Genetics and Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Medical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Surgical Oncology, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Barts Cancer Institute, Queen Mary University of London (QMUL), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, North of Scotland Regional Genetics Service, University of Aberdeen-NHS Grampian, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Cheshire and Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Leicestershire Clinical Genetics Service, University Hospitals Leicester, North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children [London] (GOSH), All Wales Medical Genetics Services, Singleton Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Lawrence], Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Klinikum Rechts der Isar, Ludwig-Maximillians University, University Hospital of Schleswig-Holstein (UKSH), University Hospital Düsseldorf, Institute of Human Genetics, Heidelberg University Hospital [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), University Hospital Carl Gustav Carus, Westfälische Wilhelms-Universität Münster (WWU), Campus Virchov Klinikum, Department of Medical Genetic, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Universität Regensburg (UR), University Hospital, Frankfurt, Breakthrough Breast Cancer Research Centre, Institute of cancer research, Service de Génétique Oncologique, Institut Curie [Paris], Service de génétique [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), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, CHU Clermont-Ferrand, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Unité d'oncogénétique, CRLCC Paul Strauss, Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, 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), Lombardi Comprehensive Cancer Center, Georgetown University, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Hereditary Cancer Program, Institut Català d'Oncologia-Hospital Duran i Reynals, Department of Pathology, Landspitali University Hospital, University of Iceland [Reykjavik], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Research Chair in Oncogenetics, Université Laval [Québec] (ULaval), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Oncology and Surgical Sciences, Universita degli Studi di Padova, Peter MacCallum Cancer Centre, Peter MacCallum Cancer Center, Department of Anatomical Pathology, Prince of Wales Hospital, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Chicago, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Departments of Medicine, and Preventive Medicine and Public Health, Creighton University, Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California-University of California, Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth)-Harold C. Simmons Comprehensive Cancer Center, Department of Pediatrics, The University of Texas Health Science Center at Houston (UTHealth), Department of Medical Genetics, University of Delaware [Newark], Epidemiology Research Program, American Cancer Society, Department of Obstetrics/Gynaecology and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Departments of Molecular VirologyImmunology and Medical Genetics and Internal Medicine, Ohio State University [Columbus] (OSU), University of Copenhagen = Københavns Universitet (KU)-Rigshospital, Odense University Hospital, Aarhus University Hospital, Vejle Hospital, Section of Genetic Oncology, University of Pisa - Università di Pisa, Lund University Hospital, Oncological Centre, Karolinska University Hospital [Stockholm], Department of Clinical and Experimental Medicine, Linköping University (LIU), Sahlgrenska University Hospital [Gothenburg], Department of Population Sciences, Beckman Research Institute of the City of Hope, UCSF Cancer Risk Program and Departments of Medicine and Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention Institute of California, Fox Chase Cancer Center, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Genetic Epidemiology Laboratory, University of Melbourne, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Columbia University [New York], Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Dermatology, University of Utah School of Medicine [Salt Lake City], This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175). ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow., for Breast Cancer Family Registry, for EMBRACE, for Ontario Cancer Genetics Network, for SWE-BRCA, for CIMBA, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, University of Pennsylvania-Abramson Cancer Center, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia [Milano] (IEO), University of Kansas Medical Center [Kansas City, KS, USA], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Julius-Maximilians-Universität Würzburg (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Georgetown University [Washington] (GU), Università degli Studi di Padova = University of Padua (Unipd), University of Pennsylvania-University of Pennsylvania, University of California (UC)-University of California (UC), Rigshospital-University of Copenhagen = Københavns Universitet (UCPH), Vejle Hospital [Danemark], University of California [San Francisco] (UC San Francisco), Lee, Andrew [0000-0003-0677-0252], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, University of Cambridge [UK] ( CAM ), University of Southampton [Southampton]-University Hospital Southampton, University of Southern California ( USC ) -Keck School of Medicine [Los Angeles], Memorial Sloan-Kettering Cancer Center-Weill Medical College of Cornell University [New York], National Cancer Institute ( NIH ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), 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 ), Instituto de investigación sanitaria de Aragón ( IIS ), National Center for Scientific Research 'Demokritos' ( NCSR ) -IRRP, IFOM, University of Florence, Università degli Studi di Roma 'La Sapienza' [Rome], Deutsches Krebsforschungszentrum ( DKFZ ), Erasmus University Medical Center-Family Cancer Clinic, University Medical Center Utrecht, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Queen Mary University of London ( QMUL ), Sheffield Children's Hospital, University Hospitals of Leicester, Great Ormond Street Hospital for Children [London] ( GOSH ), University of Kansas Medical Center, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, University Hospital Ulm, Hannover Medical School [Hannover] ( MHH ), Westfälische Wilhelms-Universität Münster ( WWU ), University Wurzburg-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, University Regensburg, INSTITUT CURIE, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire Clermont-Ferrand, Centre François Baclesse, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, 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 ), Laval University [Québec], University of Padua and Istituto Oncologico Veneto IOV - IRCCS, University of Pennsylvania Perelman School of Medicine, University of California at Los Angeles [Los Angeles] ( UCLA ), University of Texas at Houston [Houston] ( UTHealth ) -Harold C. Simmons Comprehensive Cancer Center, University of Texas Health Science, Medical University of Vienna, Mount Sinai Hospital, The Ohio State University Comprehensive Cancer Center, University of Copenhagen ( KU ) -Rigshospital, University of Pisa [Pisa], Linköping University ( LIU ), Sahlgrenska University Hospital, the Beckman Research Institute of the City of Hope, University of California [San Francisco] ( UCSF ), European Project : 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS ( 2009 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Human Genetics, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Universität Leipzig, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Roswell Park Cancer Institute [Buffalo] (RPCI)
Subjects: Risk, Heterozygote, endocrine system diseases, Population, Genes, BRCA2, Genes, BRCA1, Social Sciences, Estrogen receptor, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 610 Medical sciences Medicine, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Genotype, medicine, Humans, Genetic Predisposition to Disease, education, skin and connective tissue diseases, Estrogen Receptor Status, Alleles, 030304 developmental biology, Medicine(all), 0303 health sciences, education.field_of_study, Samhällsvetenskap, medicine.disease, 3. Good health, TOX3, Receptors, Estrogen, Cancer and Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Ovarian cancer, Receptors, Progesterone, Research Article
Abstract: [Introduction]: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. [Methods]: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. [Results]: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. [Conclusions]: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.
Published: 2011

35. NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia

Author: Nathalie Gault, Federica Ferri, Sophie Kusy, Nicolas Goardon, Paul-Henri Romeo, Bastien Gerby, Françoise Pflumio, André Baruchel, Florence Armstrong, Jean-Michel Cayuela, Delphine Gérard, Paola Ballerini, Laboratoire de biologie et de génétique du cancer [Caen] (UNICANCER - Centre François Baclesse), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Département de biostatistiques [AP-HP Hôpital Bichat, Paris], Unité de recherche clinique [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris]-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Lorraine (UL), Inorganic Chemistry Laboratory [Oxford], University of Oxford [Oxford], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), CEA Direction des Sciences du Vivant (CEA/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), University of Oxford, CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Tumor suppressor gene, T cell, [SDV]Life Sciences [q-bio], Immunology, Notch signaling pathway, [SDV.CAN]Life Sciences [q-bio]/Cancer, GATA3 Transcription Factor, Biology, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, urologic and male genital diseases, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Proto-Oncogene Proteins, Metalloproteins, Basic Helix-Loop-Helix Transcription Factors, Gene Knockdown Techniques, medicine, Animals, Humans, Immunology and Allergy, Genes, Tumor Suppressor, Transcription factor, T-Cell Acute Lymphocytic Leukemia Protein 1, ComputingMilieux_MISCELLANEOUS, Adaptor Proteins, Signal Transducing, Cell Proliferation, 030304 developmental biology, Homeodomain Proteins, Regulation of gene expression, 0303 health sciences, Gene knockdown, urogenital system, Stem Cells, Prostate, LIM Domain Proteins, DNA-Binding Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Neoplasm Transplantation, Protein Binding, Transcription Factors, TAL1
Abstract: TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1–expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1–LMO–Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-α (heterochromatin protein 1 α) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.
Published: 2010

36. Comparison between the EKFC-equation and machine learning models to predict Glomerular Filtration Rate.

Author: Nakano FK, Åkesson A, de Boer J, Dedja K, D'hondt R, Haredasht FN, Björk J, Courbebaisse M, Couzi L, Ebert N, Eriksen BO, Dalton RN, Derain-Dubourg L, Gaillard F, Garrouste C, Grubb A, Jacquemont L, Hansson M, Kamar N, Legendre C, Littmann K, Mariat C, Melsom T, Rostaing L, Rule AD, Schaeffner E, Sundin PO, Bökenkamp A, Berg U, Åsling-Monemi K, Selistre L, Larsson A, Nyman U, Lanot A, Pottel H, Delanaye P, and Vens C
Subjects: Humans, Male, Female, Middle Aged, Aged, Cystatin C blood, Adult, Creatinine blood, Kidney Function Tests methods, Glomerular Filtration Rate, Machine Learning
Abstract: In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC., (© 2024. The Author(s).)
Published: 2024
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37. Where do we stand with screening for colorectal cancer and advanced adenoma based on serum protein biomarkers? A systematic review.

Author: Grancher A, Cuissy S, Girot H, Gillibert A, Di Fiore F, and Guittet L
Subjects: Humans, Colorectal Neoplasms diagnosis, Colorectal Neoplasms blood, Biomarkers, Tumor blood, Early Detection of Cancer methods, Adenoma diagnosis, Adenoma blood, Blood Proteins analysis
Abstract: Colorectal cancer (CRC) screening has been proven to reduce both mortality and the incidence of this disease. Most CRC screening programs are based on fecal immunochemical tests (FITs), which have a low participation rate. Searching for blood protein biomarkers can lead to the development of a more accepted screening test. The aim of this systematic review was to compare the diagnostic potential of the most promising serum protein biomarkers. A systematic review based on PRISMA guidelines was conducted in the PubMed and Web of Science databases between January 2010 and December 2023. Studies assessing blood protein biomarkers for CRC screening were included. The sensitivity, specificity, and area under the ROC curve of each biomarker were collected. Among 4685 screened studies, 94 were considered for analysis. Most of them were case-control studies, leading to an overestimation of the performance of candidate biomarkers. The performance of no protein biomarker or combination of biomarkers appears to match that of the FIT. Studies with a suitable design and population, testing new assay techniques, or based on algorithms combining FIT with serum tests are needed., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Published: 2024
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38. Potential of PSMA for breast cancer in nuclear medicine: digital quantitative immunohistochemical analysis and implications for a theranostic approach.

Author: Neviere Z, Blanc-Fournier C, Guizard AV, Elie N, Giffard F, Lequesne J, Emile G, Poulain L, and Lasnon C
Subjects: Humans, Female, Male, Retrospective Studies, Middle Aged, Aged, Adult, Theranostic Nanomedicine methods, Nuclear Medicine methods, Biomarkers, Tumor metabolism, Aged, 80 and over, Precision Medicine methods, Breast Neoplasms pathology, Breast Neoplasms metabolism, Breast Neoplasms therapy, Glutamate Carboxypeptidase II metabolism, Antigens, Surface metabolism, Immunohistochemistry
Abstract: Background: Further research is still needed to fully understand the potential of prostate-specific membrane antigen (PSMA) in breast cancer (BC) and to develop and optimize targeted therapies and imaging modalities. The objective of this study was to present a comprehensive analysis of immunohistochemistry data on PSMA staining in BC and to discuss its potential value in a theranostic approach., Methods: Fifty-eight male and female patients were randomly selected from a retrospective database of patients who underwent surgery for breast cancer between January 2012 and December 2017 and for whom a specimen is available in our tumour library. Immunodetection of PSMA and CD31 was performed on serial slides. The digitized slides were reviewed and analysed by an experienced pathologist. Additionally, the corresponding TIFF images were processed to calculate the percentage of positive neovessels., Results: Eighteen patients (31.6%) had no expression, 29 (50.9%) had PSMA neovascular expression scored as "1", and 10 (17.5%) had neovascular expression scored as "2". Digital immunohistochemistry analysis for this last specific group of patients showed a median proportion of positive neovessels equal to 5% (range: 3-19). A multivariable logistic regression demonstrated that the odds of PSMA positivity were 4.55 times higher in non-luminal tumours and decreased by a factor of 0.12 in lobular subtypes. There was no association between sex or the presence of a germline BRCA1/2 mutation and PSMA expression in tumours., Conclusions: Our study highlights generally low neovascular expression of PSMA in specific histopathological subtypes of breast cancer, which will likely hamper the development of an adequate theranostic strategy., Trial Registration: The procedure has been retrospectively registered to the French National Institute for Health Data (N° F20220615153900)., (© 2024. The Author(s).)
Published: 2024
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39. CYRAD: a translational study assessing immune response to radiotherapy by photons or protons in postoperative head and neck cancer patients through circulating leukocyte subpopulations and cytokine levels.

Author: Thariat J, Pham TN, Coupey J, Clarisse B, Grellard JM, Rousseau N, Césaire M, and Valable S
Subjects: Humans, Prospective Studies, Male, Female, Middle Aged, Lymphopenia etiology, Adult, Aged, Head and Neck Neoplasms radiotherapy, Head and Neck Neoplasms immunology, Head and Neck Neoplasms blood, Head and Neck Neoplasms surgery, Proton Therapy methods, Cytokines blood, Cytokines metabolism, Leukocytes radiation effects, Leukocytes metabolism, Leukocytes immunology, Photons therapeutic use
Abstract: Background: Radiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer., Methods: CYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes., Discussion: Previous research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes., Protocol Version: Version 2.1 dated from January 18, 2023., Trial Registration: The CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961., (© 2024. The Author(s).)
Published: 2024
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40. Fine mapping of RNA isoform diversity using an innovative targeted long-read RNA sequencing protocol with novel dedicated bioinformatics pipeline.

Author: Aucouturier C, Soirat N, Castéra L, Bertrand D, Atkinson A, Lavolé T, Goardon N, Quesnelle C, Levilly J, Barbachou S, Legros A, Caron O, Crivelli L, Denizeau P, Berthet P, Ricou A, Boulouard F, Vaur D, Krieger S, and Leman R
Subjects: Humans, Alternative Splicing, Female, BRCA2 Protein genetics, BRCA1 Protein genetics, High-Throughput Nucleotide Sequencing methods, Hereditary Breast and Ovarian Cancer Syndrome genetics, Sequence Analysis, RNA methods, Computational Biology methods, RNA Isoforms genetics
Abstract: Background: Solving the structure of mRNA transcripts is a major challenge for both research and molecular diagnostic purposes. Current approaches based on short-read RNA sequencing and RT-PCR techniques cannot fully explore the complexity of transcript structure. The emergence of third-generation long-read sequencing addresses this problem by solving this sequence directly. However, genes with low expression levels are difficult to study with the whole transcriptome sequencing approach. To fix this technical limitation, we propose a novel method to capture transcripts of a gene panel using a targeted enrichment approach suitable for Pacific Biosciences and Oxford Nanopore Technologies platforms., Results: We designed a set of probes to capture transcripts of a panel of genes involved in hereditary breast and ovarian cancer syndrome. We present SOSTAR (iSofOrmS annoTAtoR), a versatile pipeline to assemble, quantify and annotate isoforms from long read sequencing using a new tool specially designed for this application. The significant enrichment of transcripts by our capture protocol, together with the SOSTAR annotation, allowed the identification of 1,231 unique transcripts within the gene panel from the eight patients sequenced. The structure of these transcripts was annotated with a resolution of one base relative to a reference transcript. All major alternative splicing events of the BRCA1 and BRCA2 genes described in the literature were found. Complex splicing events such as pseudoexons were correctly annotated. SOSTAR enabled the identification of abnormal transcripts in the positive controls. In addition, a case of unexplained inheritance in a family with a history of breast and ovarian cancer was solved by identifying an SVA retrotransposon in intron 13 of the BRCA1 gene., Conclusions: We have validated a new protocol for the enrichment of transcripts of interest using probes adapted to the ONT and PacBio platforms. This protocol allows a complete description of the alternative structures of transcripts, the estimation of their expression and the identification of aberrant transcripts in a single experiment. This proof-of-concept opens new possibilities for RNA structure exploration in both research and molecular diagnostics., (© 2024. The Author(s).)
Published: 2024
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41. Eligibility for Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in Endocrine Receptor-Positive and HER2-Negative Early Breast Cancer by Age and Type of Surgery.

Author: Houvenaeghel G, Classe JM, Chauvet MP, Colombo PE, Jouve E, Reyal F, Daraï E, Rouzier R, Faure-Virelizier C, Gimbergues P, Coutant C, Mazouni C, Azuar AS, Martino M, Bouteille C, Cohen M, and de Nonneville A
Abstract: Background: Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients. Methods: In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. Results: Eligibility rates in patients ≤40 years and >80 years who underwent mastectomy were 27.8% and 24.7% for abemaciclib, respectively, and 56.6% and 65.2% for ribociclib, respectively. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. Conclusions: If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population.
Published: 2024
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42. Contribution of [ 18 F]FET PET in the Management of Gliomas, from Diagnosis to Follow-Up: A Review.

Author: Robert JA, Leclerc A, Ducloie M, Emery E, Agostini D, and Vigne J
Abstract: Gliomas, the most common type of primary malignant brain tumors in adults, pose significant challenges in diagnosis and management due to their heterogeneity and potential aggressiveness. This review evaluates the utility of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) positron emission tomography (PET), a promising imaging modality, to enhance the clinical management of gliomas. We reviewed 82 studies involving 4657 patients, focusing on the application of [ 18 F]FET in several key areas: diagnosis, grading, identification of IDH status and presence of oligodendroglial component, guided resection or biopsy, detection of residual tumor, guided radiotherapy, detection of malignant transformation in low-grade glioma, differentiation of recurrence versus treatment-related changes and prognostic factors, and treatment response evaluation. Our findings confirm that [ 18 F]FET helps delineate tumor tissue, improves diagnostic accuracy, and aids in therapeutic decision-making by providing crucial insights into tumor metabolism. This review underscores the need for standardized parameters and further multicentric studies to solidify the role of [ 18 F]FET PET in routine clinical practice. By offering a comprehensive overview of current research and practical implications, this paper highlights the added value of [ 18 F]FET PET in improving management of glioma patients from diagnosis to follow-up.
Published: 2024
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43. Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.

Author: Poumeaud F, Morisseau M, Cabel L, Gonçalves A, Rivier C, Trédan O, Volant E, Frenel JS, Ladoire S, Jacot W, Jamelot M, Foka Tichoue H, Patsouris A, Teixeira L, Bidard FC, Loirat D, Brunet M, Levy C, Bailleux C, Cabarrou B, Deleuze A, Uwer L, Deluche E, Grellety T, Franchet C, Fiteni F, Bischoff H, Vion R, Pagliuca M, Verret B, Bécourt S, Reverdy T, de Nonneville A, and Dalenc F
Subjects: Humans, Female, Middle Aged, Aged, Retrospective Studies, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Metastasis, Progression-Free Survival, Aged, 80 and over, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Trastuzumab therapeutic use, Trastuzumab administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Camptothecin administration & dosage, Receptor, ErbB-2 metabolism, Immunoconjugates therapeutic use, Immunoconjugates administration & dosage
Abstract: Background: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody-drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown., Methods: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC., Results: One hundred and seventy-nine patients were included: the majority with HR-negative tumours received SG first (ADC1) (n = 100/108) while most with HR-positive tumours received T-DXd first (n = 56/71). Median progression-free survival 2 was short: 2.7 months (95% CI: 2.4-3.3) in the whole population, respectively, 3.1 (95% CI: 2.6-3.6) and 2.2 months (95% CI: 1.9-2.7) for patients receiving T-DXd or SG second (ADC2). Intermediary lines of chemotherapy between ADC1 and ADC2 had no impact. Primary resistance to ADC2 occurred in 54.4% of patients. Certain patients showed initial response to ADC2., Conclusions: Clinical benefit of sequentially administered SG and T-DXd is limited for most patients. Nevertheless, a subset of patients might benefit-on the short term-from a second ADC. Additional studies are needed to identify patients who could benefit from two ADCs with similar payloads., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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44. Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET.

Author: Gilbert A, Tudor M, Delaunay A, Leman R, Levilly J, Atkinson A, Castéra L, Dinischiotu A, Savu DI, Valable S, and Chevalier F
Subjects: Humans, Cell Line, Tumor, Radiation-Sensitizing Agents pharmacology, Cell Survival drug effects, Cell Survival radiation effects, Phthalazines pharmacology, Bone Neoplasms drug therapy, Bone Neoplasms pathology, Bone Neoplasms radiotherapy, Bone Neoplasms metabolism, Piperazines pharmacology, DNA Repair drug effects, Chondrosarcoma radiotherapy, Chondrosarcoma drug therapy, Chondrosarcoma pathology, Chondrosarcoma genetics, Chondrosarcoma metabolism, Chondrocytes drug effects, Chondrocytes radiation effects, Chondrocytes metabolism, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Linear Energy Transfer
Abstract: Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested.
Published: 2024
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45. Role of Oxidative Stress Signaling, Nrf2, on Survival and Stemness of Human Adipose-Derived Stem Cells Exposed to X-rays, Protons and Carbon Ions.

Author: Hammad M, Salma R, Balosso J, Rezvani M, and Haghdoost S
Abstract: Some cancers have a poor prognosis and often lead to local recurrence because they are resistant to available treatments, e.g., glioblastoma. Attempts have been made to increase the sensitivity of resistant tumors by targeting pathways involved in the resistance and combining it, for example, with radiotherapy (RT). We have previously reported that treating glioblastoma stem cells with an Nrf2 inhibitor increases their radiosensitivity. Unfortunately, the application of drugs can also affect normal cells. In the present study, we aim to investigate the role of the Nrf2 pathway in the survival and differentiation of normal human adipose-derived stem cells (ADSCs) exposed to radiation. We treated ADSCs with an Nrf2 inhibitor and then exposed them to X-rays, protons or carbon ions. All three radiation qualities are used to treat cancer. The survival and differentiation abilities of the surviving ADSCs were studied. We found that the enhancing effect of Nrf2 inhibition on cell survival levels was radiation-quality-dependent (X-rays > proton > carbon ions). Furthermore, our results indicate that Nrf2 inhibition reduces stem cell differentiation by 35% and 28% for adipogenesis and osteogenesis, respectively, using all applied radiation qualities. Interestingly, the results show that the cells that survive proton and carbon ion irradiations have an increased ability, compared with X-rays, to differentiate into osteogenesis and adipogenesis lineages. Therefore, we can conclude that the use of carbon ions or protons can affect the stemness of irradiated ADSCs at lower levels than X-rays and is thus more beneficial for long-time cancer survivors, such as pediatric patients.
Published: 2024
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46. Particle Beam Radiobiology Status and Challenges: A PTCOG Radiobiology Subcommittee Report.

Author: Ahmad R, Barcellini A, Baumann K, Benje M, Bender T, Bragado P, Charalampopoulou A, Chowdhury R, Davis AJ, Ebner DK, Eley J, Kloeber JA, Mutter RW, Friedrich T, Gutierrez-Uzquiza A, Helm A, Ibáñez-Moragues M, Iturri L, Jansen J, Morcillo MÁ, Puerta D, Kokko AP, Sánchez-Parcerisa D, Scifoni E, Shimokawa T, Sokol O, Story MD, Thariat J, Tinganelli W, Tommasino F, Vandevoorde C, and von Neubeck C
Abstract: Particle therapy (PT) represents a significant advancement in cancer treatment, precisely targeting tumor cells while sparing surrounding healthy tissues thanks to the unique depth-dose profiles of the charged particles. Furthermore, their linear energy transfer and relative biological effectiveness enhance their capability to treat radioresistant tumors, including hypoxic ones. Over the years, extensive research has paved the way for PT's clinical application, and current efforts aim to refine its efficacy and precision, minimizing the toxicities. In this regard, radiobiology research is evolving toward integrating biotechnology to advance drug discovery and radiation therapy optimization. This shift from basic radiobiology to understanding the molecular mechanisms of PT aims to expand the therapeutic window through innovative dose delivery regimens and combined therapy approaches. This review, written by over 30 contributors from various countries, provides a comprehensive look at key research areas and new developments in PT radiobiology, emphasizing the innovations and techniques transforming the field, ranging from the radiobiology of new irradiation modalities to multimodal radiation therapy and modeling efforts. We highlight both advancements and knowledge gaps, with the aim of improving the understanding and application of PT in oncology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
Published: 2024
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47. Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.

Author: Dufresne A, Pokras S, Meurgey A, Chabaud S, Toulmonde M, Bompas E, Le Cesne A, Robin YM, Duffaud F, Valentin T, El Zein S, Leroux A, Dubray-Longeras P, Firmin N, de Pinieux G, Noal S, Delfour C, Bollard J, Tonon L, Biette A, Gadot N, Attignon V, Jean-Denis M, Woessner M, Klohe E, Thayaparan T, Eleftheriadou I, Blouch K, Nathenson MJ, and Blay JY
Subjects: Humans, Male, Female, Retrospective Studies, Prognosis, Middle Aged, Adult, Aged, Biomarkers, Tumor metabolism, Neoplasm Metastasis, Sarcoma, Synovial genetics, Sarcoma, Synovial metabolism, Sarcoma, Synovial pathology, Sarcoma, Synovial mortality, Membrane Proteins metabolism, Antigens, Neoplasm metabolism
Abstract: Background: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed., Patients and Methods: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes., Results: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting., Conclusions: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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48. Cognition and Return to Work Status 2 Years After Breast Cancer Diagnosis.

Author: Lange M, Lequesne J, Dumas A, Clin B, Vaz-Luis I, Pistilli B, Rigal O, Lévy C, Lerebours F, Martin AL, Everhard S, Menvielle G, and Joly F
Subjects: Humans, Female, Middle Aged, Adult, Cognitive Dysfunction etiology, France epidemiology, Prospective Studies, Depression, Breast Neoplasms psychology, Breast Neoplasms complications, Return to Work statistics & numerical data, Cognition
Abstract: Importance: Return to work after breast cancer (BC) treatment depends on several factors, including treatment-related adverse effects. While cancer-related cognitive impairment is frequently reported by patients with BC, to date, no longitudinal studies have assessed its association with return to work., Objective: To examine whether cognition, assessed using objective and subjective scores, was associated with return to work 2 years after BC diagnosis., Design, Setting, and Participants: In a case series of the French Cancer Toxicities (CANTO) cohort, a study of patients with stage I to III BC investigated cognition from April 2014 to December 2018 (2 years' follow-up). Participants included women aged 58 years or younger at BC diagnosis who were employed or looking for a job., Main Outcomes and Measures: The outcome was return to work assessed 2 years after BC diagnosis. Objective cognitive functioning (tests), cognitive symptoms, anxiety, depression, and fatigue were prospectively assessed at diagnosis (baseline), 1 year after treatment completion, and 2 years after diagnosis. Multivariable logistic regression models were used to explain return to work status at year 2 according to each cognitive measure separately, adjusted for age, occupational class, stage at diagnosis, and chemotherapy., Results: The final sample included 178 women with BC (median age: 48.7 [range, 28-58] years), including 37 (20.8%) who did not return to work at year 2. Patients who returned to work had a higher (ie, professional) occupational class and were less likely to have had a mastectomy (24.1% vs 54.1%; P < .001). Return to work at year 2 was associated with lower overall cognitive impairment (1-point unit of increased odds ratio [1-pt OR], 0.32; 95% CI, 0.13-0.79; P = .01), higher working memory (1-pt OR, 2.06; 95% CI, 1.23-3.59; P = .008), higher processing speed (1-pt OR, 1.97; 95% CI, 1.20-3.36; P = .01) and higher attention performance (1-pt OR, 1.63; 95% CI, 1.04-2.64; P = .04), higher perceived cognitive abilities (1-pt OR, 1.12; 95% CI, 1.03-1.21; P = .007), and lower depression (1-pt OR, 0.83; 95% CI, 0.74-0.93; P = .001) at year 2 assessment. Return to work at year 2 was associated with several measures assessed at baseline and year 1: higher processing speed (1-pt OR, 2.38; 95% CI, 1.37-4.31; P = .003 and 1.95; 95% CI, 1.14-3.50; P = .02), higher executive performance (1-pt OR, 2.61; 95% CI, 1.28-5.75; P = .01, and 2.88; 95% CI, 1.36-6.28; P = .006), and lower physical fatigue (10-pt OR, 0.81; 95% CI, 0.69-0.95; P = .009 and 0.84; 95% CI, 0.71-0.98; P = .02)., Conclusions and Relevance: In this case series study of patients with BC, return to work 2 years after diagnosis was associated with higher cognitive speed performance before and after BC treatment. Cognitive difficulties should be assessed before return to work to propose suitable management.
Published: 2024
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49. Local relapse patterns after preoperative radiotherapy of limb and trunk wall soft tissue sarcomas: Prognostic role of imaging and pathologic response factors.

Author: Cuenin M, Levy A, Peiffert D, Sunyach MP, Ducassou A, Cordoba A, Gillon P, Thibouw D, Lapeyre M, Lerouge D, Helfre S, Leroux A, Salleron J, Sirveaux F, Marchal F, P Teixeira, Debordes PA, and G Vogin
Abstract: Purpose: To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS)., Methods and Materials: This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the "Conticabase". Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR., Results: 257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates < 20 %; and NUS with cellularity rates < 20 %, which shared similar prognostic risks with LG sarcomas., Conclusions: HG and LG tumors have different morphological and biological behaviors in response to RT. Combination of cellularity rate with histotype could be a major prognostic for LR. Patients with undifferentiated HG sarcomas with cellularity rates ≥ 20 % after preoperative RT had the highest risk of LR and disease-specific death., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)
Published: 2024
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50. External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer.

Author: Oufkir N, Rouzier R, Paoletti X, and Bonneau C
Subjects: Humans, Female, Middle Aged, Aged, Adult, CA-125 Antigen blood, Neoadjuvant Therapy methods, Platinum therapeutic use, ROC Curve, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial pathology, Drug Resistance, Neoplasm, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Ovarian Neoplasms mortality, Neoplasm Recurrence, Local
Abstract: Background: Neoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KELIM) and the Platinum Resistant Recurrence (PtRR) Score have been proposed as markers of tumor chemosensitivity. The aim of our study was to validate these tools for predicting platinum sensitivity in a real-world population of patients with advanced EOC treated with neoadjuvant chemotherapy., Experimental Design: All patients with advanced EOC treated with neoadjuvant chemotherapy at the Institut Curie between 2000 and 2015 were included. The Std KELIM was calculated with the CA-125 concentrations during the first 100 days of chemotherapy. The predictive value of Std KELIM and PtRR scores for the risk of subsequent PtRR was assessed using receiver operating characteristic (ROC) curve analysis, logistic regression and calibration curve. Kaplan-Meier survival analysis was performed for the treatment-free interval from platinum (TFIp) therapy and overall survival (OS)., Results: Std KELIM data were available for 149 patients. The AUC was 0.67 for PtRR. A low Std KELIM was significantly associated with PtRR (OR = 0.19 (95% CI [0.06, 0.53], p = 0.002)) according to the univariate analysis. The calibration curve of the PtRR showed a slight but significant underestimation (p = 0.02) of the probability of platinum resistance. Favorable Std KELIM (≥ 1) alone and combined with the completeness of surgery were associated with significantly better survival in terms of TFIp and OS., Conclusions: Std KELIM is an early prognostic marker of chemosensitivity in a real-life setting complementary to surgical status. It could help the clinician in the early management of patients by identifying those with a worse prognosis., (© 2024. The Author(s).)
Published: 2024
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