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1. Systemic chemotherapy plus cetuximab after complete surgery in the treatment of isolated colorectal peritoneal carcinoma: COCHISE phase II clinical trial

Author: Serge Evrard, Grégoire Desolneux, Carine Bellera, Thomas Esnaud, Yves Bécouarn, Denis Collet, Najim Chafai, Francois Marchal, Laurent Cany, Emilie Lermite, Michel Rivoire, and Simone Mathoulin-Pélissier
Subjects: Colorectal cancer, Peritoneal carcinomatosis, Cytoreductive surgery, KRAS gene, Hyperthermic intraperitoneal chemotherapy, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract: Abstract Objective The primary objective of this non-randomised phase II study was to evaluate the combination of systemic chemotherapy plus cetuximab after complete cytoreductive surgery (CCS) for treatment of isolated colorectal peritoneal carcinoma (CRPC). This multicentre, prospective phase II clinical trial was conducted in seven national cancer referral centres, however research published during study recruitment indicated cetuximab treatment as ineffective in patients with mutated KRAS genes, leading to an additional exclusion criterion to the current protocol, excluding patients with mutated KRAS genes. This significantly impacted recruitment and the study did not achieve the necessary recruitment of 46 patients. Results Fourteen patients underwent CCS and were included in the study, however one did not provide informed consent and another received only one cycle of chemotherapy leading to 12 patients in the per protocol population for analysis. Adjuvant Folfox Cetuximab was administered when CCS was achieved for patients > 18 years with histologically proven CRPC and no other metastatic disease (liver, lungs, lymphadenopathy, etc.). CRPC median index was 5.00 (range: 1–17). Median PFS was 12.3 months [95% CI (3.7–28.2)] with 8.3% [95% CI (0.5–31.1)] and 0% PFS at 3 and 5 years respectively. Median OS was 43.4 months [95% CI (16.8–60)]. Trial registration Clinical Trials NCT00766142, October 3, 2008. Retrospectively registered
Published: 2019
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2. Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False

Author: Marie Desjardin, Benjamin Bonhomme, Brigitte Le Bail, Serge Evrard, Véronique Brouste, Gregoire Desolneux, Marianne Fonck, Yves Bécouarn, and Dominique Béchade
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes. Patients and methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis. Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex ( P = .01), pre-operative platelets 0.36 ( P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m 2 ( P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively). Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.
Published: 2019
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3. Pancreatic Acinar Cell Carcinoma

Author: Dominique Béchade, Marie Desjardin, Emma Salmon, Grégoire Désolneux, Yves Bécouarn, Serge Evrard, and Marianne Fonck
Subjects: Acinar cell carcinoma, Pancreas, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Pancreatic acinar cell carcinoma (ACC) is a rare malignant neoplasm that accounts for 1–2% of all pancreatic neoplasms. Here we report two cases of ACC and describe their clinical features, the therapies used to treat them, and their prognosis. The first patient was a 65-year-old woman who had an abdominal CT scan for a urinary infection. Fortuitously, a rounded and well-delimited corporeal pancreatic tumor was discovered. An endoscopic ultrasound (EUS)-guided fine needle aspiration revealed an ACC. During the puncture, a hypoechoic cavity appeared inside the lesion, corresponding to a probable necrotic area. Treatment consisted of a distal splenopancreatectomy. The second patient was a 75-year-old man who complained of abdominal pain. An abdominal CT scan showed a cephalic pancreatic lesion and two hepatic metastases. An EUS-guided fine needle aspiration showed a pancreatic ACC. The patient received chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen), which enabled an objective response after 6 cycles.
Published: 2016
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4. Cytoreductive surgery of colorectal peritoneal metastases: outcomes after complete cytoreductive surgery and systemic chemotherapy only.

Author: Grégoire Désolneux, Camille Mazière, Jérémy Vara, Véronique Brouste, Marianne Fonck, Dominique Béchade, Yves Bécouarn, and Serge Evrard
Subjects: Medicine, Science
Abstract: BackgroundCytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC's role is less certain.MethodOverall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only.ResultsMedian peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1).ConclusionWith an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.
Published: 2015
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5. Pulmonary Thermal Ablation Enables Long Chemotherapy-Free Survival in Metastatic Colorectal Cancer Patients

Author: Xavier Buy, Yves Becouarn, Vittorio Catena, Véronique Verger, Véronique Brouste, Jean Palussière, Jean-Thomas Perez, Eric Brudieux, Dominique Béchade, Patrick Texereau, L. Cany, Valérie Le Brun-Ly, Laure Vayre, and Mariane Fonck
Subjects: Ablation Techniques, Male, medicine.medical_specialty, Lung Neoplasms, Percutaneous, Radiofrequency ablation, Colorectal cancer, medicine.medical_treatment, Thermal ablation, Gastroenterology, Disease-Free Survival, 030218 nuclear medicine & medical imaging, Metastasis, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Lung, Aged, Chemotherapy, business.industry, medicine.disease, Survival Rate, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Colorectal Neoplasms, Cardiology and Cardiovascular Medicine, business
Abstract: Chemotherapy (ct) is the preferred treatment option in metastatic colorectal cancer (mCRC). The objective of the study was to determine the overall survival (OS), disease-free survival (DFS) and ct-free survival (CFS) of pulmonary thermal ablation (TA) and its place in the treatment of mCRC. All consecutive patients treated (over 11 years) with percutaneous TA for lung metastasis of colorectal origin were reviewed. All sequences of treatments were considered. We determined the OS, DFS and CFS of pulmonary TA. Two hundred and nine patients underwent 323 TA procedures for 630 lung metastases. Majority of the metastases (71.5%) were unilateral with a median diameter of 10 mm (2–46). A single metastasis was treated in 95 patients (45.5%), and 2–8 in 114 patients (54.5%). One hundred and thirty-two patients (63.2%) had only a single procedure, 77 patients (36.8%) had 2–5 procedures. Following the first TA (n = 209), 125 patients (59.8%) resumed ct. Sixty-four out of the 126 patients presenting lung progression were treated again with TA. The median CFS was 12.2 months (95% CI: 10.3–17.7). Patients with no extra-pulmonary metastases showed a statistically better CFS than those who had extra-pulmonary metastases with a median of 20.9 and 9.2 months, respectively (p
Published: 2018
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6. Toxicité hépatique des inhibiteurs des tyrosines kinases : mécanismes en cause et conséquences pratiques

Author: Yves Becouarn, Marie Desjardin, Camille Chakiba, Dominique Béchade, and Marianne Fonck
Subjects: Liver injury, Cancer Research, Side effect, business.industry, Patient risk, Hematology, General Medicine, medicine.disease, Bioinformatics, 030226 pharmacology & pharmacy, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Toxicity, medicine, Radiology, Nuclear Medicine and imaging, Liver function, business, Adverse effect, Practical implications, Tyrosine kinase
Abstract: Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which can progress to severe liver injury in a minority of patients if treatment is maintained despite ongoing injury. This risk requires careful patient management to maintain treatment benefit without harm. This review highlights the various mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites and how this leads to toxicity. These critical events depend of the drug-specific characteristics of each TKI and the patient risk factors, especially genetic characterization. With improved understanding of the mechanisms leading to hepatotoxicity, several strategies have been adopted to prevent or treat this side effect. Recommendations on liver function liver test monitoring have been proposed according to each TKI.
Published: 2018
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7. Systemic chemotherapy plus cetuximab after complete surgery in the treatment of isolated colorectal peritoneal carcinoma: COCHISE phase II clinical trial

Author: Thomas Esnaud, Emilie Lermite, Francois Marchal, Simone Mathoulin-Pélissier, Carine Bellera, Denis Collet, Yves Becouarn, M. Rivoire, Gregoire Desolneux, L. Cany, Serge Evrard, and Najim Chafai
Subjects: 0301 basic medicine, Oncology, Male, Colorectal cancer, Phases of clinical research, lcsh:Medicine, Cetuximab, Kaplan-Meier Estimate, medicine.disease_cause, 0302 clinical medicine, FOLFOX, Antineoplastic Combined Chemotherapy Protocols, Cytoreductive surgery, 030212 general & internal medicine, Prospective Studies, lcsh:QH301-705.5, Peritoneal Neoplasms, education.field_of_study, General Medicine, Cytoreduction Surgical Procedures, Middle Aged, Research Note, Hyperthermic intraperitoneal chemotherapy, Female, KRAS gene, KRAS, Colorectal Neoplasms, medicine.drug, Adult, medicine.medical_specialty, Population, Hemorrhage, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, education, lcsh:Science (General), Retrospective Studies, business.industry, lcsh:R, medicine.disease, Clinical trial, 030104 developmental biology, lcsh:Biology (General), business, Peritoneal carcinomatosis, lcsh:Q1-390
Abstract: Objective The primary objective of this non-randomised phase II study was to evaluate the combination of systemic chemotherapy plus cetuximab after complete cytoreductive surgery (CCS) for treatment of isolated colorectal peritoneal carcinoma (CRPC). This multicentre, prospective phase II clinical trial was conducted in seven national cancer referral centres, however research published during study recruitment indicated cetuximab treatment as ineffective in patients with mutated KRAS genes, leading to an additional exclusion criterion to the current protocol, excluding patients with mutated KRAS genes. This significantly impacted recruitment and the study did not achieve the necessary recruitment of 46 patients. Results Fourteen patients underwent CCS and were included in the study, however one did not provide informed consent and another received only one cycle of chemotherapy leading to 12 patients in the per protocol population for analysis. Adjuvant Folfox Cetuximab was administered when CCS was achieved for patients > 18 years with histologically proven CRPC and no other metastatic disease (liver, lungs, lymphadenopathy, etc.). CRPC median index was 5.00 (range: 1–17). Median PFS was 12.3 months [95% CI (3.7–28.2)] with 8.3% [95% CI (0.5–31.1)] and 0% PFS at 3 and 5 years respectively. Median OS was 43.4 months [95% CI (16.8–60)]. Trial registration Clinical Trials NCT00766142, October 3, 2008. Retrospectively registered
Published: 2019

8. Sorafenib alone vs. sorafenib plus GEMOX as 1st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial

Author: Yves Becouarn, Jean-Marie Peron, Mohamed Ramdani, Georges-Philippe Pageaux, Sylvain Poujol, Marc Ychou, S. Thezenas, Valérie Boige, Hélène de Forges, Jean-Frédéric Blanc, Eric Assenat, Jean-François Seitz, Philippe Merle, Olivier Bouché, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cancer de Montpellier (ICM), Université de Montpellier (UM), Institut Bergonié [Bordeaux], UNICANCER, CHU Marseille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Saint-André, Centre Hospitalier Universitaire de Reims (CHU Reims), 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), and Institut Gustave Roussy (IGR)
Subjects: Sorafenib, Adult, Male, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, GemOx, Neutropenia, urologic and male genital diseases, Gastroenterology, Deoxycytidine, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Chemotherapy, Humans, heterocyclic compounds, Protein Kinase Inhibitors, neoplasms, Aged, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Gemcitabine, female genital diseases and pregnancy complications, digestive system diseases, 3. Good health, Oxaliplatin, Portal vein thrombosis, Oncology, 030220 oncology & carcinogenesis, Randomized controlled trials, Female, business, medicine.drug
Abstract: International audience; BACKGROUND:Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients.METHODS:Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate.RESULTS:Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18).CONCLUSIONS:Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.
Published: 2019
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9. Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study

Author: David Sefrioui, Julien Edeline, M. Baconnier, Karine Le Malicot, Barbara Dauvois, Alexandra Heurgue, Jean-Louis Jouve, Sébastien Dharancy, Julien Vergniol, Yves Rinaldi, Hervé Perrier, Maryline Debette-Gratien, Yves Becouarn, Mohamed Hebbar, Anthony Turpin, Christine Silvain, Côme Lepage, Thierry Lecomte, Gael Deplanque, Thierry de Baere, and Isabelle Ollivier-Hourmand
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, urologic and male genital diseases, Placebo, Placebo group, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Sunitinib, medicine, Humans, Chemoembolization, Therapeutic, Hepatology, business.industry, Liver Neoplasms, Liver failure, medicine.disease, Acute toxicity, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Dose reduction, business, Liver Failure, medicine.drug
Abstract: Summary Background Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection. Aims We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure. Methods Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated. Results No bleeding complication was reported. One and two liver failures were respectively observed in sunitinib and placebo patients. Compliance to sunitinib treatment was acceptable. Sunitinib dose reduction occurred in 37% of patients due to acute toxicity. Main grade 3–4 toxicities were: thrombocytopenia, neutropenia, increased bilirubin, increased ALT and asthenia. In the sunitinib group, the median PFS and OS were 9.05 [5.81;11.63] and 25.0 [13.5;36.8] months, respectively. In the placebo group, the median PFS and OS were 5.51 [4.14;7.79] and 20.5 [15.1;30.6] months, respectively. Conclusions TACE plus sunitinib in the first-line therapy for patients with HCC not suitable for surgical resection was feasible. ClinicalTrials.gov number NCT01164202.
Published: 2021
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10. Pancreatic Acinar Cell Carcinoma

Author: Marie Desjardin, Gregoire Desolneux, Marianne Fonck, Dominique Béchade, Emma Salmon, Serge Evrard, and Yves Becouarn
Subjects: Endoscopic ultrasound, Pathology, medicine.medical_specialty, Abdominal pain, Case Report, Lesion, 03 medical and health sciences, 0302 clinical medicine, Pancreatic tumor, medicine, lcsh:RC799-869, Pancreas, Acinar cell carcinoma, medicine.diagnostic_test, business.industry, Gastroenterology, medicine.disease, Gemcitabine, stomatognathic diseases, medicine.anatomical_structure, Fine-needle aspiration, 030220 oncology & carcinogenesis, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business, medicine.drug, Pancreatic Acinar Cell Carcinoma
Abstract: Pancreatic acinar cell carcinoma (ACC) is a rare malignant neoplasm that accounts for 1–2% of all pancreatic neoplasms. Here we report two cases of ACC and describe their clinical features, the therapies used to treat them, and their prognosis. The first patient was a 65-year-old woman who had an abdominal CT scan for a urinary infection. Fortuitously, a rounded and well-delimited corporeal pancreatic tumor was discovered. An endoscopic ultrasound (EUS)-guided fine needle aspiration revealed an ACC. During the puncture, a hypoechoic cavity appeared inside the lesion, corresponding to a probable necrotic area. Treatment consisted of a distal splenopancreatectomy. The second patient was a 75-year-old man who complained of abdominal pain. An abdominal CT scan showed a cephalic pancreatic lesion and two hepatic metastases. An EUS-guided fine needle aspiration showed a pancreatic ACC. The patient received chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen), which enabled an objective response after 6 cycles.
Published: 2016
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11. Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Author: Mireille Mousseau, Eric Francois, A. Fatisse, A. Bedjaoui, Abakar Mahamat, C. Lombard-Bohas, J. Ezenfis, Marc Porneuf, F. Subtil, M. Tissot, Emilie Maillard, M. Fayolle, J.F. Dor, A. Votte, P. Chiappa, P. Prost, Denis Cléau, P. Bergerault, J.C. Souquet, K. Beerblock, P. Chatrenet, J.M. Sabate, M. Carreiro, S. Beorchia, Vincent Hautefeuille, Jessika Moreau, N. Delas, C. Vilain, Christian Borel, Franck Audemar, M. Duluc, Touraj Mansourbakht, Bernard Denis, Gael Deplanque, Jean-Marc Phelip, C. Brezault, Anne Thirot-Bidault, L. Gasnault, Jean-Louis Jouve, Y. Rinaldi, B. Leduc, Y. Courouble, A. Alessio, Matthieu Schnee, P. Cassan, Antoine Adenis, Jocelyne Provencal, A. Botton, Laurent Cany, Françoise Desseigne, Marie-Christine Kaminsky, Mohamed Ramdani, B. Lafforgue, L. Rob, J.C. Barbare, S. Jacquot, A. Zaanan, J.-Y. Douillard, C. Cornila, B. Rhein, Benjamin Linot, Z. Ladhib, D. Zylberait, Cedric Lecaille, N. Hess-Laurens, H. Brixi-Benmansour, C. Rebischung, C. Giraud, L. Stefani, D. Pillon, J.P. Lafargue, J. Forestier, P. Laplaige, C. Paoletti, S. Lavau Denes, Etienne Suc, A. Patenotte, E. Echinard, François-Xavier Caroli-Bosc, D. Goldfain, V. Quentin, Hervé Perrier, J.D. Grangé, A. Marre, M. Baconnier, Bruno Coudert, Thomas Walter, R. Benoit, A. Blanchi, A.C. Dupont-Gossart, Emilie Barbier, X. Coulaud, D. Besson, Isabelle Trouilloud, D. Sevin-Robiche, M Giovannini, O. Boulat, C. Lobry, H. Castanie, Y. Molin, Thomas Aparicio, Valérie Boige, P. Lehair, J.P. Robin, J.P. Latrive, J. Goineau, Clément Belletier, G. Medinger, C. Lepere, Philippe Rougier, N. Bouaria, E. Carola, V. Derias, Bernard Paillot, Yves Becouarn, F. Kikolski, Martin Combe, Julie Vincent, C. Briac-Levaché, C. Becht, François Ghiringhelli, J. Charneau, Dany Gargot, Julien Vergniol, Denis Péré-Vergé, P. Pienkowski, Patrick Texereau, I. Baumgaertner, J.P. Ramain, Pierre-Luc Etienne, P. Claudé, Jean Francois Paitel, J.P. Plachot, M.-C. Clavero-Fabri, P. Geoffroy, A. Cadier-Lagnes, Y. Le Bricquir, S. Fratte, O. Favre, Aimery de Gramont, J. Butel, David Tougeron, B. Winkfield, E. Janssen, J. Meunier, Julien Volet, N. Gérardin, D. Soubrane, Vincent Bourgeois, Xavier Adhoute, Y.H. Lam, P.A. Haineaux, A. Rotenberg, J-B. Bachet, C. Berger, F. Almaric, J. Tuaillon, G. Gatineau-Saillant, F. Zerouala-Boussaha, E. Cuillerier, R. Lamy, D. Luet, D. Baudet-Klepping, E.A. Pariente, M. Gignoux, J. Martin, M. Blasquez, Romain Coriat, C. Bineau, J. Boutin, A. Aouakli, F. Dewaele, A.M. Queuniet, V. Sebbagh, P. Couzigou, N. Barrière, Faiza Khemissa, P. Follana, Laurence Chone, F. Petit-Laurent, N. Abdelli, Olivier Capitain, D. Bechade, Corinne Sarda, J.P. Herr, P. Pouderoux, Julien Taieb, M. Pauwels, E. Zrihen, L. Wander, Gael Goujon, G. Boilleau-Jolimoy, Anne Thirot Bidault, B. Landi, V. Jestin Le Tallec, Jaafar Bennouna, O. Berthelet, M. Glikmanas, H. Salloum, Côme Lepage, Thierry Lecomte, P. Amoyal, C. Platini, Veronique Guerin-Meyer, B. Garcia, Laetitia Dahan, Pascal Burtin, J. Villand, S. Nguyen, A. Roussel, F. Di Fiore, S. Oddou-Lagraniere, J.P. Aucouturier, Veronique Lorgis, Gerard Cavaglione, J.P. Lagasse, Dominique Auby, Pierre Michel, F. Bonnetain, Gilles Breysacher, R. Mackiewicz, Philippe Ruszniewski, T. Morin, J. Thaury, Clara Locher, J.M. Vantelon, S. Nasca, J.P. Barbieux, H. Maechel, Y. Coscas, May Mabro, S. Montembault, P. Novello, M. Charbit, J. Deguiral, A. Gagnaire, D. Festin, A. Gueye, Hélène Senellart, Achim Weber, Nadia Bouarioua, Jérôme Dauba, Michel Ducreux, Jean-Luc Raoul, G. Coulanjon, J.N. Vaillant, S. Chaussade, A. Gilbert, Anne-Laure Villing, Dominique Genet, P. Martin, M. Ben Abdelghani, M.P. Galais, A. Azzedine, A. Lemaire, C. Barberis, C. Buffet, J. Egreteau, G. Roquin, M. Mornet, Isabelle Cumin, M. Pelletier, P. Feydy, J. Lacourt, T. Chatellier, Jean-Louis Legoux, M. Benchalal, I. Graber, S. Nahon, P. Pantioni, A. Hollebecque, M. Zawadi, Pascal Hammel, M. Mignot, Roger Faroux, J. Lafon, Mohamed Gasmi, Jean-Philippe Spano, S. Pesque-Penaud, C. de la Fouchardiere, J. Cretin, Olivier Bouché, D. Smith, E. Norguet-Monnereau, G. Bordes, Sylvain Manfredi, Thévenet P, Herve Lacroix, E. Dorval Danquechin, Eric Terrebonne, Laurent Bedenne, P. Godeau, David Malka, V. Veuillez, Emmanuel Mitry, F. Riot, Sandrine Hiret, François Morvan, M.C. Gouttebel, Jean-François Seitz, Karine Bouhier-Leporrier, N. Stremsdoerfer, P. Souillac, M. Mozer, C. Couffon, F. Husseini, J.M. Cheula, J.-M. Gornet, K. Slimane Fawzi, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris-Saclay, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Privé des Côtes d'Armor (HPCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de la Loire [Saint-Priest en Jarez], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service De Gastroenterologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Hôpital Louis Pasteur [Colmar] (CH Colmar), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Overweight, Gastroenterology, Pooled analysis, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, Individual data, medicine, Overall survival, Humans, Neoplasm Metastasis, Objective response, Aged, 2. Zero hunger, Clinical Trials as Topic, Prognostic factor, business.industry, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Normal weight, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract: IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI
Published: 2018
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12. Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

Author: Jaafar Bennouna, Yves Becouarn, C. Lepere, for Prodige investigators, Gercor, Fédération Française de Cancérologie Digestive, Laurent Mineur, Gaël Deplanque, Aimery de Gramont, Louis Marie Dourthe, Ahmed Khalil, Joëlle Egreteau, Marine Hug de Larauze, Unicancer, Jean-Baptiste Bachet, Roger Faroux, Jérôme Desramé, Olivier Dupuis, S. Fratte, Jeremie Bez, Thierry André, Marc Ychou, François Ghiringhelli, Olivier Bouché, May Mabro, Julien Taieb, Dewi Vernerey, Marie Pierre Galais, Christophe Louvet, Jérôme Dauba, Sophie Paget-Bailly, Franck Bonnetain, Benoist Chibaudel, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut Sainte Catherine [Avignon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital privé Jean Mermoz, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CH Belfort-Montbéliard, Fédération Francophone de la Cancérologie Digestive, FFCD, Centre Hospitalier Layné, Institut Mutualiste de Montsouris (IMM), 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), Clinique Victor Hugo, Institut Bergonié [Bordeaux], Hôpital Foch [Suresnes], Groupe Hospitalier Bretagne Sud (GHBS), Hôpital universitaire Robert Debré [Reims], Groupe Hospitalier Paris Saint-Joseph, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Clinique Sainte Anne [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Institut hospitalier Franco-Britannique [Levallois-Perret], Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), CHU Saint-Antoine [APHP], Groupe cooperateur multidisciplinaire en oncologie (GERCOR), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Inserm UMR 1098, Centre René Gauducheau - ICO, institut de Cancerologie de l'Ouest, Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Bergonié - CRLCC Bordeaux, centre hospitalier Bretagne sud, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), CHU Pitié-Salpêtrière [APHP], and CHU Tenon [APHP]
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, medicine, education, education.field_of_study, Chemotherapy, business.industry, medicine.disease, 3. Good health, Oxaliplatin, 030104 developmental biology, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, business, Adjuvant, medicine.drug
Abstract: Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.
Published: 2018
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13. Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)

Author: Thomas Aparicio, Emmanuelle Samalin, Pierre Michel, Olivier Bouché, Blaise Batumona, Laurent Bedenne, Christophe Cellier, Benoit Chibaudel, Yves Becouarn, Marc Pocard, Yann Parc, Pauline Afchain, Nicolas Carrere, Christophe Locher, Centre Hospitalier de Meaux, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Purpan (CHU Purpan), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Rouen, Normandie Université (NU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-APHP, Institut hospitalier Franco-Britannique [Levallois-Perret], and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: medicine.medical_specialty, Colorectal cancer, Small bowel adenocarcinoma, Colonoscopy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Adenocarcinoma, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Intestinal Neoplasms, Intestine, Small, National recommendations, medicine, Humans, Stage (cooking), Intersectoral Collaboration, Neoplasm Staging, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Cancer, Platinum salts, medicine.disease, 3. Good health, Surgery, Clinical Practice, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, 030211 gastroenterology & hepatology, France, business
Abstract: IF 3.061; International audience; BackgroundThis document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016.MethodThis collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009).ResultsSmall bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement).ConclusionFew specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.
Published: 2018
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14. Secondary Metastases Resection After Bevacizumab Plus Irinotecan-Based Chemotherapy in First-Line Therapy of Metastatic Colorectal Cancer in a Real-Life Setting: Results of the ETNA Cohort

Author: Rosine Guimbaud, Magali Rouyer, Jérémy Jové, Denis Smith, Alain Ravaud, Pernelle Noize, Philip Robinson, Nicole Tubiana-Mathieu, Christophe Laurent, Pierre Michel, A. Balestra, Nicholas Moore, Annie Fourrier-Réglat, and Yves Becouarn
Subjects: Male, Cancer Research, medicine.medical_specialty, Pathology, Bevacizumab, Colorectal cancer, Radiofrequency ablation, medicine.medical_treatment, Population, Irinotecan, Gastroenterology, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), education, Aged, Neoplasm Staging, Chemotherapy, education.field_of_study, business.industry, Liver Neoplasms, Metastasectomy, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Survival Rate, Oncology, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cohort, Camptothecin, Female, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, Complication, Follow-Up Studies, medicine.drug
Abstract: Resection of metastases after chemotherapy improves survival outcomes of patients with initially inoperable metastatic colorectal cancer (mCRC), yet little data is available for those treated in the first-line setting with bevacizumab plus irinotecan. To provide data on this, the present study described the subgroup of the ETNA cohort who underwent metastases surgery. The population of operated patients was described according to metastatic site (exclusively hepatic, non-exclusively hepatic, and non-hepatic). Factors associated with overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox analysis. A total of 76 patients (21.1 % of the ETNA cohort) underwent metastases resection: 50 % male, median age 61.9 years, 85.5 % ECOG ≤ 1, and median duration of bevacizumab use 7.2 months. No surgery-related deaths were observed and 30.6 % of patients had at least one post-operative complication, mainly infections (11.8 % of resections), bleeding complications (3.5 %), or delayed wound healing (2.4 %). Complete remission was higher for those with exclusively hepatic metastases (22/32, 68.8 %) than those with non-exclusively hepatic metastases (12/24, 50.0 %), or non-hepatic metastases (12/20, 60.0 %). Among operated patients, 52.6 % had died after 5 years of follow-up. In multivariable analysis at 2 years of follow-up, death (HR 0.09 [95 % CI 0.02-0.35]) and progression (HR 0.35 [95 % CI 0.23-0.56]) were less likely for patients with complete remission (CR) after surgery R0-R1 or radiofrequency ablation (RFA) [CR RFA] compared with those who were not resected or with R2 resection. In real-life practice, bevacizumab with irinotecan in first-line therapy for mCRC allows secondary resection of metastases and survival is more favourable in those with complete remission (R0-R1/CR RFA).
Published: 2015
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15. Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition

Author: Serge Evrard, Olivier Degrandi, Benjamin Bonhomme, Gregoire Desolneux, Marianne Fonck, Dominique Béchade, Yves Becouarn, Véronique Brouste, and Marie Desjardin
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Tumor burden, Antineoplastic Agents, 030230 surgery, Resection, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Risk Factors, medicine, Clinical endpoint, Hepatectomy, Humans, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, business.industry, Liver Neoplasms, Liver failure, General Medicine, Middle Aged, Ablation, Combined Modality Therapy, Embolization, Therapeutic, Surgery, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Portal vein embolization, Female, Neoplasm Grading, business, Colorectal Neoplasms
Abstract: Background The definition of parenchymal sparing surgery (PSS) for colorectal liver metastases (CRLM) diverges requiring a clarification of the concept. Method A consecutive series of patients were treated by PSS for their CRLMs, either by resection or intra-operative ablation (IOA), whenever possible a one-stage surgery and minimal usage of portal vein embolization. Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Results Three hundred and eighty-seven patients underwent a PSS out of which 328 patients received a median of 9 pre-operative cycles of chemotherapy. One hundred and twenty-eight patients had a major resection, combined with IOA in 137 patients and IOA alone in 50 cases. The 5yr-overall survival was 50.3%. There was no difference in post-operative complications between minor and major resections, validating our PSS definition based on the Tumor burden/Healthy liver ratio and not just the retrieved volume. Conclusions PSS is defined as a high ratio of tumoral burden per specimen retrieved while favoring one-stage surgery approach. Our series, using combined resections and IOAs, matches this definition well. Furthermore, complications were correlated neither to chemotherapy nor to liver-induced toxicities, contrary to extended hepatectomies.
Published: 2017

16. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author: Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), 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 National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [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), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-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) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract: IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.
Published: 2017
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17. Hyperplasie nodulaire régénérative secondaire à une chimiothérapie à base d’oxaliplatine

Author: Isabelle Soubeyran, Marianne Fonck, Serge Evrard, Gregoire Desolneux, Dominique Béchade, and Yves Becouarn
Subjects: business.industry, Carcinoma, medicine, MEDLINE, General Medicine, medicine.disease, Nuclear medicine, business, Liver pathology, Oxaliplatin, medicine.drug
Published: 2013
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18. Unresectable colorectal cancer liver metastases treated by intraoperative radiofrequency ablation with or without resection19

Author: Carine Bellera, Simone Mathoulin-Pélissier, Caroline Lalet, E. Lermite, Michel Rivoire, Marina Pulido, Marianne Fonck, J.-P. Arnaud, S. Evrard, and Yves Becouarn
Subjects: Chemotherapy, medicine.medical_specialty, business.industry, Radiofrequency ablation, Colorectal cancer, medicine.medical_treatment, Phases of clinical research, medicine.disease, law.invention, Surgery, law, Clinical endpoint, Medicine, Progression-free survival, Hepatectomy, business, Survival rate
Abstract: Background Despite neoadjuvant chemotherapy, few patients with colorectal cancer liver metastases (CRLM) are eligible for liver resection. The aim of the present study was to investigate the efficacy of intraoperative radiofrequency ablation (IRFA) in the treatment of unresectable CRLM. Methods Patients with unresectable metastases confined to the liver were eligible for this prospective, multicentre phase II study conducted between 2003 and 2008. They received IRFA treatment either with or without parenchymal resection, and underwent clinical and pathological examinations. The primary endpoint was complete hepatic response at 3 months. Overall, event-free and local progression-free survival, morbidity and quality of life were also examined. Results Fifty-two patients were included, all of whom received neoadjuvant chemotherapy. They had a median of 5 (range 1–13) metastases, mostly bilateral or recurrent. A complete hepatic response was observed in 39 patients (75 (95 per cent confidence interval (c.i.) 61 to 86) per cent). Of ten patients with hepatic recurrence at 3 months, two relapses were at the site of ablation. Median follow-up was 2·9 (95 per cent c.i. 2·5 to 3·6) years. The 1-year local progression-free survival rate was 46 (95 per cent c.i. 32 to 59) per cent, the 3-year event-free survival rate was 10 (95 per cent c.i. 4 to 21) per cent and the 5-year overall survival rate was 43 (95 per cent c.i. 21 to 64) per cent. Twenty patients had postoperative complications, including one death. Quality of life increased over time for patients without disease progression. Conclusion IRFA, either with or without resection, is a promising treatment option for patients with unresectable CRLM. Registration number: NTC00210106 (http://www.clinicaltrials.gov).
Published: 2012
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19. Chemotherapy does not impair parenchymal sparing surgery to treat colorectal liver metastases

Author: Serge Evrard, M. Fonck, Marie Desjardin, G. Desolneux, Dominique Béchade, Véronique Brouste, Yves Becouarn, and Benjamin Bonhomme
Subjects: Cancer Research, Chemotherapy, medicine.medical_specialty, Oncology, business.industry, medicine.medical_treatment, Parenchyma, medicine, business, Surgery
Published: 2017
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20. Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: A first-line phase II study

Author: Carine Bellera, C. Mertens, Simone Mathoulin-Pélissier, Pierre Soubeyran, Laurent Traissac, Jérôme Dauba, Jean-Louis Legoux, Yves Becouarn, René Brunet, Muriel Rainfray, Denis Smith, Dominique Auby, L. Cany, Eric Terrebonne, and Marianne Fonck
Subjects: Male, Oncology, medicine.medical_specialty, Colorectal cancer, Leucovorin, Folinic acid, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, FOLFIRI Regimen, Humans, Medicine, Aged, Aged, 80 and over, Hepatology, business.industry, Gastroenterology, Cancer, medicine.disease, Irinotecan, Regimen, FOLFIRI, Camptothecin, Female, Fluorouracil, business, Febrile neutropenia, medicine.drug
Abstract: Summary Objective Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients. Design In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m2], fluorouracil [5-FU] [400 mg/m2] and folinic acid 400 mg/m2 or 200 mg/m2 of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months. Results Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5–56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4–46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment. Conclusions Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.
Published: 2011
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21. Eight dietary advice cards to address the needs of elderly cancer patients treated with palliative chemotherapy: INOGAD study

Author: P. Soubeyran, J. Vergnol, Joël Ceccaldi, M. Fonck, C. Lecaille, E. Terrebonne, J. F. Blanc, F. Chomy, D. Smith, Isabelle Bourdel-Marchasson, C. Blanc-Bisson, D. Béchade, N. Houede, J. Durrieu, and Yves Becouarn
Subjects: Gynecology, medicine.medical_specialty, Oncology, Palliative treatment, business.industry, Dietary supplement, medicine, business
Abstract: Objectifs Le conseil dietetique dans l’etude interventionnelle randomisee INOGAD reposait sur l’utilisation de fiches de conseil expliquees au patient lors d’entretien en face-a-face au cours des cures successives de chimiotherapie. L’objectif de cette etude ancillaire etait d’en evaluer l’observance.
Published: 2011
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22. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment

Author: A. Kramar, P. Afchain, Rosine Guimbaud, M. Ychou, Thomas Aparicio, Emmanuelle Samalin, Françoise Desseigne, Antoine Adenis, Fadi Abbas, Emmanuel Mitry, Julien Edeline, Simon Thezenas, Yves Becouarn, Olivier Bouché, O. Romano, and Etienne Dorval
Subjects: Adult, Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Esophageal Neoplasms, Adenocarcinoma, Neutropenia, Irinotecan, Gastroenterology, Folinic acid, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, FOLFIRI Regimen, Humans, Medicine, Aged, Retrospective Studies, Aged, 80 and over, Hepatology, business.industry, Middle Aged, medicine.disease, Antineoplastic Agents, Phytogenic, Surgery, Docetaxel, Fluorouracil, FOLFIRI, Camptothecin, Female, Esophagogastric Junction, business, medicine.drug, Epirubicin
Abstract: Summary Objectives The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. Methods Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m 2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400 mg/m 2 i.v. over two hours followed by 5-FU 400 mg/m 2 i.v. bolus then 5-FU 2400 mg/m 2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. Results There was no difference between chemonaive and not chemonaive pts treated as first-line in terms of response rate 37% (95% CI: 25–50) vs 44% (95% CI: 21–69), median PFS, 6.7 (95% CI: 5.5–9.9) vs 5.3 months (95% CI: 3.6–6.9) ( P = 0.25), and OS, 13.1 (95% CI: 11.7–18.7) vs 8.8 months (95% CI: 7.3–15.6) ( P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8–39) vs 22% (95% CI: 6–48), median PFS, four months (95% CI: 2.8–5.4) vs 3.5 months (95% CI: 2.3–4.5) ( P = 0.56), and OS, 10.4 months (95% CI: 5.4–14.4) vs 5.3 months (95% CI: 3.5–11.3) ( P = 0.58), respectively. The global grade 3–4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). Conclusions This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.
Published: 2011
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23. Induction chemotherapy (CT) with FOLFIRINOX or FOLFOX/FOLFIRI, plus cetuximab (CET) or bevacizumab (BEV) (by RAS status), in patients (pts) with primarily unresectable colorectal liver metastases (CRLM): Results of the randomized UNICANCER PRODIGE 14-ACCORD 21 (METHEP-2) trial

Author: Claire Jouffroy-Zeller, Marie Pierre Galais, Philippe Houyau, François Ghiringhelli, Marc Ychou, Anne Mercier Blas, René Adam, Thomas Aparicio, Laurent Mineur, Eric Assenat, Rosine Guimbaud, Antoine Adenis, Marion Chauvenet, Olivier Bouché, Faiza Khemissa, Simon Thezenas, Michel Rivoire, Eric Francois, Yves Becouarn, and Franck Audemar
Subjects: Oncology, Liver surgery, Cancer Research, medicine.medical_specialty, Cetuximab, Bevacizumab, business.industry, FOLFIRINOX, Induction chemotherapy, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, FOLFIRI, 030211 gastroenterology & hepatology, In patient, business, medicine.drug
Abstract: 3535Background: pts with unresectable CRLM who respond to induction CT allowing curative-intent liver surgery have longer overall survival (OS) than pts who do not. Triplet (3-) or doublets (2-) CT...
Published: 2018
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24. Randomized clinical trial of telephoned-based physical activity intervention in onco-geriatric patients

Author: Eric Terrebonne, Sandrine Lavau-Denes, Haritz Arrieta, Isabelle Bourdel-Marchasson, V. Servent, Marianne Fonck, Aline Maillard, Brigitte Maget, Sophie C. Regueme, Jessica Durrieu, Christophe Laurent, Jérôme Dauba, Rodolphe Thiébaut, Cyril Astrugue, and Yves Becouarn
Subjects: Cancer Research, medicine.medical_specialty, business.industry, Physical activity, Cancer, Physical function, medicine.disease, law.invention, Oncology, Randomized controlled trial, law, Intervention (counseling), medicine, Physical therapy, business
Abstract: 10031Background: Cancer in older patient favors the loose of physical function. Physical activity could be a key factor to diminish the age and cancer-related decline. Methods: We conducted a multi...
Published: 2018
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25. KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications

Author: Antoine Italiano, Thibault Fabas, René Brunet, Isabelle Soubeyran, Florence Pedeutour, Eric Francois, Jean Gugenheim, Marie-Christine Saint-Paul, Isabelle Hostein, Marianne Fonck, Yves Becouarn, Serge Evrard, Daniel Benchimol, Laboratory of Solid Tumors Genetics, Nice University Hospital, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Department of Digestive Surgery, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Chirurgie Digestive et Transplantation Hépatique, Hôpital Archet II, Service d'Anatomie et Cytologie Pathologiques, and Hôpital Pasteur [Nice] (CHU)
Subjects: Male, Oncology, endocrine system diseases, Colorectal cancer, medicine.disease_cause, Polymerase Chain Reaction, 0302 clinical medicine, Surgical oncology, Epidermal growth factor receptor, Neoplasm Metastasis, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Aged, 80 and over, 0303 health sciences, Cetuximab, biology, DNA, Neoplasm, Middle Aged, Prognosis, 3. Good health, ErbB Receptors, 030220 oncology & carcinogenesis, Female, KRAS, Colorectal Neoplasms, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Antineoplastic Agents, Adenocarcinoma, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Growth factor receptor, Proto-Oncogene Proteins, Internal medicine, Biomarkers, Tumor, medicine, Humans, Panitumumab, neoplasms, Aged, Neoplasm Staging, 030304 developmental biology, business.industry, Wild type, medicine.disease, digestive system diseases, Mutation, ras Proteins, Cancer research, biology.protein, Surgery, business
Abstract: International audience; BACKGROUND: KRAS and BRAF mutations in primary colorectal tumors (PT) are predictive of nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). The question of primary resistance to anti-EGFR treatment as a result of the presence of KRAS or BRAF mutations only in metastases has been raised but not resolved. METHODS: We analyzed the mutational status of KRAS and BRAF in 64 new patients with mCRC and performed a systematic review of published data from 285 patients. RESULTS: A total of 285 and 95 matched PT/metastases were available for the analysis of the KRAS and the BRAF status, respectively. An identical mutational pattern of KRAS in PT and the matching metastases were reported in all the cases but 14 (5%). In six cases (2%), KRAS was mutated in the PT and wild type in the metastatic site, whereas in eight cases (3%), KRAS was wild type in the PT and mutated in the metastatic site. An identical mutational pattern of BRAF in PT and the matching metastases was reported in all but two cases (3%). In one case (1.5%), BRAF was mutated in the PT and wild type in the metastatic site, whereas in one case (1.5%), BRAF was wild type in the PT and mutated in the metastatic site. CONCLUSIONS: The acquisition by metastases of a KRAS or a BRAF mutation that was not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.
Published: 2010
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26. Traitement par radiofréquence des tumeurs hépatiques et pulmonaires

Author: Jean Palussière, Michèle Kind, Edouard Descat, Françoise Bonichon, Alain Ravaud, F. Chomy, Yves Becouarn, A. Avril, and Marianne Fonck
Subjects: Cancer Research, medicine.medical_specialty, Radiofrequency ablation, business.industry, medicine.medical_treatment, Cancer, Hematology, General Medicine, medicine.disease, Ablation, law.invention, Surgery, Oncology, law, Hepatocellular carcinoma, medicine, Carcinoma, Radiology, Nuclear Medicine and imaging, Liver cancer, Lung cancer, business, Prospective cohort study
Abstract: Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over the last fifteen years in the field of oncology. RF directed toward a specific tumor mass is known to be very effective (over 90%) for treating tumors less than 2.5 cm. RF is used for patients with early-stage lung or liver cancers who are not surgical candidates, With improvements in systemic therapy, increasing interest in the use of local therapy for metastases has arisen. Eradication of residual metastases via local therapies has a sense in patients with stabilized disease. Nonsurgical alternative like RF has become popular because it is less invasive than surgery and has demonstrated great efficiency. Nevertheless prospective randomized trials to compare RF with surgery are difficult to achieve, prospective studies are needed to better evaluate the technique.
Published: 2009
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27. Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort

Author: Alain Ravaud, Angela Grelaud, Jérémy Jové, Magali Rouyer, Nicole Tubiana-Mathieu, Annie Fourrier-Réglat, Pernelle Noize, Philip Robinson, Rosine Guimbaud, Denis Smith, Yves Becouarn, and Nicholas Moore
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, genetic structures, Bevacizumab, Colorectal cancer, Leucovorin, Disease-Free Survival, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Neoplasm Metastasis, Survival rate, Aged, Proportional Hazards Models, business.industry, Middle Aged, medicine.disease, Oxaliplatin, Survival Rate, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, FOLFIRI, Camptothecin, Female, Fluorouracil, Geriatrics and Gerontology, business, Colorectal Neoplasms, Cohort study, medicine.drug
Abstract: Effectiveness of bevacizumab for metastatic colorectal cancer in elderly patients has been investigated in observational studies, mainly associated with oxaliplatin-based regimens. Here, using the ETNA cohort in which the majority of patients received bevacizumab+FOLFIRI, the effectiveness of this combination in elderly patients is explored.Patients initiating first-line therapy with bevacizumab between January 2006 and December 2007 were identified in 28 French centres and followed for 24months. Vital status was collected over 36months. In the present analysis those who received FOLFIRI were retained (85% of those included), and patients were stratified by age (70/≥70years). The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS), and Cox models were used to assess the independent effect of age on survival outcomes.Among the 351 patients who received bevacizumab+FOLFIRI, 33.9% were aged ≥70years, 66.1%70years. Respectively 15.1% and 9.5% of patients had ECOG-PS ≥2; 49.6% and 40.1% used 'stop-and-go' treatment scheduling; and 56.3% and 44.4% experienced grade 3/4 adverse events. Overall response rate was 58.8% and 62.5%. Median [95% confidence interval, CI] OS was respectively 24.1 [20.4; 26.2] and 28.5 [25.0; 31.0] months; age≥70years and ECOG-PS≥2 were significantly associated with death. Median PFS [95% CI] was respectively 10.9 [9.4; 12.6] and 9.8 [9.2; 11.2] months; hepatic metastases was associated with progression, and age ≥70years was associated with progression after 14months of follow-up but not before.The present study adds to the literature on the safe and beneficial effect of bevacizumab in the elderly receiving FOLFIRI regimen.
Published: 2015

28. Cytoreductive Surgery of Colorectal Peritoneal Metastases: Outcomes after Complete Cytoreductive Surgery and Systemic Chemotherapy Only

Author: Dominique Béchade, Serge Evrard, Jeremy Vara, Yves Becouarn, Marianne Fonck, Véronique Brouste, Gregoire Desolneux, and Camille Maziere
Subjects: Male, medicine.medical_specialty, Science, medicine.medical_treatment, Antineoplastic Agents, Metastasis, Peritoneal Neoplasm, Surgical oncology, medicine, Humans, Survival analysis, Peritoneal Neoplasms, Chemotherapy, Multidisciplinary, business.industry, Standard treatment, medicine.disease, Combined Modality Therapy, Survival Analysis, Surgery, Conventional PCI, Peritoneal Cancer Index, Medicine, Female, business, Colorectal Neoplasms, Research Article
Abstract: BackgroundCytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC's role is less certain.MethodOverall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only.ResultsMedian peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1).ConclusionWith an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.
Published: 2015

29. Could bipolar vessel sealers prevent bile leaks after hepatectomy?

Author: René Brunet, Caroline Larrue, Serge Evrard, Marianne Fonck, Simone Mathoulin-Pélissier, and Yves Becouarn
Subjects: Adult, Aged, 80 and over, Male, medicine.medical_specialty, business.industry, medicine.medical_treatment, Anastomosis, Surgical, Liver Neoplasms, Middle Aged, Protein coagulation, Surgery, Hepatic parenchyma, Catheter Ablation, Electrocoagulation, Feasibility Studies, Hepatectomy, Humans, Medicine, Female, business, Aged
Abstract: The aim of this work was to test the feasibility of using a bipolar low thermal acting system inducing collagenic sealing but not protein coagulation to secure hepatic parenchyma cutting.Thirty consecutive hepatectomies were carried out using kellyclasy plus ligatures and clips (controls), while the following 50 hepatectomies used kellyclasy plus bipolar vessels sealer (BVS). Blood loss, duration of hepatic pedicle clamping, length of hospital stay, and complications were recorded.There was no statistically significant difference in blood loss and duration of clamping between controls and BVS. Specific complications (9/21 in the control group vs 1/49 for the BVS group, p0.00045) and length of hospital stay (14 days in the control group vs 11 days in the BVS group, p0.014) were statistically lower in BVS group than in the controls, mainly due to prevention of bile duct leakages.Our data suggest that BVS may be particularly efficient to achieve bilistasis leading to the highest level of safety in performing hepatectomies. Further studies are now needed to confirm its superiority on the classical biliary ducts occlusion techniques.
Published: 2006
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30. Cancer of the pancreas

Author: Françoise Mornex, Pascal Hammel, Thierry André, Yves Becouarn, Laurent Palazzo, and François Lacaine
Subjects: Oncology, medicine.medical_specialty, Pancreatic disease, Palliative care, MEDLINE, Pancreaticoduodenectomy, Internal medicine, medicine, Humans, Neoplasm Staging, Clinical Trials as Topic, business.industry, General surgery, Palliative Care, Gastroenterology, Cancer, General Medicine, medicine.disease, Neoadjuvant Therapy, Pancreatic Neoplasms, medicine.anatomical_structure, Practice Guidelines as Topic, Stents, Neoplasm staging, France, Pancreas, business
Published: 2006
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31. Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients

Author: Jean-Luc Raoul, E. Francois, J.-Y. Douillard, Jaafar Bennouna, E. Gamelin, Philippe Barthélémy, Jean Francois Seitz, A. Fandi, Thierry Conroy, S. Nasca, F. Bertheault-Cvitkovic, Bernard Paillot, Yves Becouarn, and M. Ychou
Subjects: Adult, Male, medicine.medical_specialty, Organoplatinum Compounds, Pyridines, Nausea, medicine.medical_treatment, Phases of clinical research, Thiophenes, Adenocarcinoma, Neutropenia, Gastroenterology, Drug Administration Schedule, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Ambulatory Care, medicine, Humans, Infusions, Intravenous, Aged, Neoplasm Staging, Chemotherapy, Dose-Response Relationship, Drug, Performance status, business.industry, Biopsy, Needle, Hematology, Middle Aged, medicine.disease, Survival Analysis, Oxaliplatin, Surgery, Treatment Outcome, Oncology, Quinazolines, Vomiting, Female, medicine.symptom, Colorectal Neoplasms, business, Raltitrexed, Follow-Up Studies, medicine.drug
Abstract: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients.Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance statusor=2 and good baseline organ function. Most (56%) had only one disease site. All patients were assessed for safety, and 66 of 69 eligible patients were assessed for response.A total of 404 cycles were administered, with a median of six cycles per patient (range 1-12 cycles). Relative dose intensities were 0.98 and 0.98 for oxaliplatin and raltitrexed, respectively. The most common grade 3-4 toxicities (National Cancer Institute Common Toxicity Criteria) among treated patients were as follows: neutropenia (21 patients, 30%), asthenia (eight, 11%), diarrhea (12, 17%), liver function test abnormalities (24, 34%), nausea (nine, 13%) and vomiting (nine, 13%). Two treatment-related deaths occurred (hematotoxicity in one patient and gastrointestinal toxicity in the other) and two further deaths were possibly related to treatment (hepatic dysfunction in one patient and neuropathy in the other). Thirty-seven objective responses (one complete) were obtained [objective response rate 54%; 95% confidence interval (CI) 42% to 65%] in eligible patients. The median response duration was 8.5 months (95% CI 6.7-12.2 months), while median progression-free and overall survival among eligible patients were 6.2 (95% CI 5.1-6.9 months) and 14.6 months (95% CI 11.0-18.9 months), respectively.The present study confirms the feasibility of the raltitrexed plus oxaliplatin combination and its activity in non-pretreated advanced colorectal cancer patients.
Published: 2002
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32. Three versus six months’ adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: Per-protocol, subgroups and long-lasting neuropathy results

Author: Gael Deplanque, Dewi Vernerey, Jérôme Dauba, L. Mineur, C. Louvet, May Mabro, C. Lepere, Olivier Dupuis, Jaafar Bennouna, O. Bouche, T. Andre, Roger Faroux, S. Fratte, Jérôme Desramé, Yves Becouarn, F. Bonnetain, Marc Ychou, Julien Taieb, A. de Gramont, and Joëlle Egreteau
Subjects: 0301 basic medicine, Oncology, Long lasting, medicine.medical_specialty, Chemotherapy, Intention-to-treat analysis, business.industry, medicine.medical_treatment, Hematology, Colon cancer stage iii, Oxaliplatin, Stage III Colon Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Adjuvant, medicine.drug
Published: 2017
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33. Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition

Author: Yves Becouarn, Dominique Béchade, Véronique Brouste, Marie Desjardin, Benjamin Bonhomme, Gregoire Desolneux, Marianne Fonck, and Serge Evrard
Subjects: stomatognathic diseases, Cancer Research, medicine.medical_specialty, Oncology, Colorectal cancer, business.industry, Public health, medicine, medicine.disease, business, Surgery
Abstract: e15013 Background: Colorectal cancer metastases (CRLM) are major public health issue. Recently, surgeons have advocated the use of parenchymal sparing surgery (PSS) however, a common definition of the concept is lacking.To clarify and try to validate the concept of PSS to treat CRLM through the available retrospectives studies, including ours. Methods: Retrospective analysis of a cohort of patients treated by combined resections and intra-operative ablation (IOA) based on PSS, prospectively recorded in a database from 2003 to 2015 in a regional referral cancer center. All the patients benefited from the same strategy, constituting a homogenous series.PSS consists of using resection or IOA in order to spare the healthy parenchyma. One-stage is favored over two-stage surgery and use of portal vein embolization was restricted to the minimum.Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Liver toxicities and overall survival were also scrutinized. Results: Three hundred and eighty-seven patients underwent a PSS out of which 348 patients received a median of 9 pre-operative cycles of oxaliplatin or irinotecan with targeted therapies for half of them. Resection was major in 128 patients, combined with IOA in 137 patients and IOA alone in 50 cases. Thirty-eight patients had a PVO by strict necessity. The 5yr-overall survival was 50.3%. Seventy-eight patients had a complication > grade 3 out of which 10 patients died. Nine patients had a liver failure (LF) grade B and C and four died. There was no difference in post-operative complications comparing minor and major resections, validating our PSS definition. Chemotherapy and liver toxicity were not related to more post-operative complications. Only one patient died from a primitive LF. Conclusions: With PSS, healthy liver is no more a target. Routine use of chemotherapy does not impair the results and severe LFs are rare. PSS is the optimal strategy to treat CRLM. Definition of PSS cannot be based just on the retrived volume but on the ratio Tumor burden/Healthy liver. A major hepatectomy can be a PSS and a minor may not be one. That is why PSS defintion must be clarify especially for further prospective validations.
Published: 2017
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34. Three versus six months adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: The French participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project

Author: Jaafar Bennouna, Dewi Vernerey, Julien Taieb, Olivier Dupuis, Roger Faroux, Céline Lepère, Joëlle Egreteau, Christophe Louvet, May Mabro, Aimery de Gramont, Marc Ychou, Laurent Mineur, Olivier Bouché, Jérôme Desramé, Jérôme Dauba, Franck Bonnetain, Nasredine Aissat, Gael Deplanque, Yves Becouarn, and Thierry André
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Adjuvant chemotherapy, medicine.medical_treatment, Population, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, 030212 general & internal medicine, Stage (cooking), education, Chemotherapy, education.field_of_study, business.industry, Surgery, Oxaliplatin, Stage III Colon Cancer, 030211 gastroenterology & hepatology, business, Adjuvant, medicine.drug
Abstract: 3500 Background: The IDEA international collaboration was established to combine data from 6 randomized trials to assess whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) for 3-year disease free survival (DFS) in stage III colon cancer (CC). Methods: French IDEA randomized patients (pts) between 3M and 6M of CT with mFOLFOX6 or XELOX (physician/pts choice). DFS was estimated using the Kaplan–Meier method and described using 3 years DFS rate. Results: Among 2022 randomized pts between May 2009 and May 2014, 2010 (99.4%) received CT and were enrolled in the mITT population: 49.9 and 50.1% in 3M and 6M, respectively. 99.5% of the mITT pts had stage III (N1: 74.9%; N2: 25.2%); median age 63.9 years; mFOLFOX6: 90% and XELOX 10% of pts. DFS median follow-up is 50.2 months. There were 578 DFS events (314 in 3M and 264 in 6M arm) leading to a 3-year DFS rate of 72.1% in the 3M vs. 75.7% in the 6M (HR=1.24; 95%CI 1.05–1.46, p=0.0112). For pts receiving mFOLFOX6, 3-year DFS rate was 72.0% in the 3M vs. 76.3% in the 6M (HR=1.27; 95%CI 1.07–1.51 p=0.0069). 94.2% and 78.0% of pts completed 3 and 6 months of CT, respectively. Median oxaliplatin doses intensity were 96.9% in 3M and 72.1% in 6M (495.0 and 735.1 mg/m2). By considering the neuropathy grade with 15375 neuropathy longitudinal measurements the overall maximal neuropathy grade 0-1/2/3-4 was 63.6/28.5/7.9% in 3M and 33.4/41.3/25.3% in 6M; p
Published: 2017
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35. Low response rate after cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: Long-term results of the UNICANCER ACCORD 16 phase II trial

Author: Beata Juzyna, Julie Leclercq, Laurent Miglianico, Yves Becouarn, Patrick Ezra, Isabelle Martel-Lafay, Thierry Conroy, Anne Delarochefordiere, C. Lemanski, D. Azria, Katty Malekzadeh, David Malka, A. Levy, Jean-Pierre Pignon, Eric Deutsch, Emmanuel Rio, Radiothérapie moléculaire (UMR 1030), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), 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 du Cancer de Montpellier (ICM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Curie [Paris], Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Onco-génétique, Département de médecine oncologique [Gustave Roussy], UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre hospitalier privé Saint-Grégoire, 35768 Saint-Grégoire, France, parent, Institut Bergonié [Bordeaux], Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), UNICANCER-UNICANCER, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, Institut de Cancérologie de l'Ouest, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)
Subjects: Oncology, medicine.medical_specialty, Locally advanced, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, Clinical Trials, Phase II as Topic, Internal medicine, medicine, Humans, Anal cancer, Radiology, Nuclear Medicine and imaging, In patient, ComputingMilieux_MISCELLANEOUS, Response rate (survey), business.industry, Chemoradiotherapy, Hematology, Long term results, Anus Neoplasms, medicine.disease, 3. Good health, Clinical trial, business, medicine.drug
Abstract: International audience
Published: 2015
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36. Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial†

Author: L. Miglianico, D. Azria, E. Paris, Patrick Ezra, C. Lemanski, Beata Juzyna, Katty Malekzadeh, Anne Delarochefordiere, Emmanuel Rio, J.P. Pignon, Eric Deutsch, Isabelle Martel-Lafay, T. Conroy, Yves Becouarn, David Malka, Antonin Levy, Institut Gustave Roussy (IGR), CRLCC Val d'Aurelle - Paul Lamarque, Institut Curie [Paris], Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre Hospitalier Privé Saint-Grégoire, Institut Bergonié [Bordeaux], UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie, Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Institut Bergonié - CRLCC Bordeaux
Subjects: Male, MESH: Radiotherapy, Phases of clinical research, Gastroenterology, chemoradiotherapy, MESH: Anus Neoplasms, 0302 clinical medicine, MESH: Cetuximab, cetuximab, Medicine, MESH: Chemoradiotherapy, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, Cetuximab, Hematology, Middle Aged, phase II, Anus Neoplasms, targeted therapy, MESH: Drug-Related Side Effects and Adverse Reactions, 3. Good health, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Female, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, anal cancer, Population, Antibodies, Monoclonal, Humanized, Loading dose, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Anal cancer, Humans, education, Adverse effect, 030304 developmental biology, Aged, MESH: Humans, Radiotherapy, business.industry, toxicity, MESH: Adult, medicine.disease, MESH: Male, Surgery, MESH: Cisplatin, MESH: Antibodies, Monoclonal, Humanized, MESH: Disease-Free Survival, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cisplatin, Neoplasm Recurrence, Local, business, MESH: Fluorouracil, MESH: Female, Chemoradiotherapy
Abstract: Background The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). Patients and methods Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m2 with a loading dose of 400 mg/m2 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. Results The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18–27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%–86%), 62% (95% CI: 36%–82%), and 92% (95% CI: 67%–99%), respectively. Conclusion CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. Eudra CT No 2007-007029-38.
Published: 2013
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37. Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort

Author: Rosine Guimbaud, Magali Rouyer, Pernelle Noize, Alain Ravaud, Olivier Bernard, Nicholas Moore, Denis Smith, Jacques Benichou, Annie Fourrier-Réglat, and Yves Becouarn
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, Antineoplastic Agents, Kaplan-Meier Estimate, Antibodies, Monoclonal, Humanized, Irinotecan, Disease-Free Survival, Cohort Studies, Young Adult, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Molecular Targeted Therapy, Neoplasm Metastasis, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Confidence interval, Surgery, Clinical trial, Regimen, Treatment Outcome, Oncology, Cohort, Camptothecin, Female, France, business, Colorectal Neoplasms, medicine.drug, Cohort study
Abstract: Although the real-life benefits of bevacizumab may differ from clinical trials, observational data are rare. In this cohort study, the effectiveness of bevacizumab in first-line treatment of metastatic colorectal cancer was investigated. Patients initiating bevacizumab between January 2006 and December 2007 were identified in 28 French centres. Outcomes were investigated in the whole cohort and in those with irinotecan-based treatment that was used in the pivotal clinical trial; patients were stratified using inclusion/exclusion criteria of the pivotal clinical trial (PCT) (eligible for the PCT, not eligible or unclassifiable). The Kaplan–Meier method estimated progression-free survival (PFS) and overall survival (OS). A total of 411 patients were included: 57 % male, median age 65.1 years, 78 % Eastern Cooperative Oncology Group performance status ≤1, 88 % irinotecan-based regimen, median duration of bevacizumab use 5.5 months, median OS = 25.3 months (95 % confidence interval, CI [23.3; 27.0]) and median PFS = 10.1 months (95 % CI [9.5; 11.0]). Among the 360 patients who received irinotecan-based chemotherapy, 144 would have been eligible for the PCT, 194 not eligible and 22 unclassifiable. Median OS in those considered eligible was 29.1 (95 % CI [25.4; 33.6]) and in those considered not eligible this was 24.9 months (95 % CI [21.3; 26.9]); median PFS was respectively 11.5 months (95 % CI [10.3; 12.0]) and 9.4 months (95 % CI [8.8; 10.3]). The effectiveness of bevacizumab was found to be similar to that found in other studies including clinical trials which is reassuring.
Published: 2013

38. FOLFIRINOX combined to targeted therapy according RAS status for colorectal cancer patients with liver metastases initially non-resectable: A phase II randomized Study—Prodige 14 – ACCORD 21 (METHEP-2), a unicancer GI trial

Author: Faiza Khemissa, Michel Rivoire, Eric Francois, Thomas Aparicio, Franck Audemar, Driffa Moussata, Philippe Houyau, Simon Thezenas, Marie-Pierre Galais, René Adam, Yves Becouarn, François Ghiringhelli, Eric Assenat, Rosine Guimbaud, Laurent Mineur, Olivier Bouché, Trevor Stanbury, Marc Ychou, and Anne Mercier-Blas
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, FOLFIRINOX, business.industry, medicine.medical_treatment, Induction chemotherapy, medicine.disease, Targeted therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, business
Abstract: 3512Background: Liver metastases (LM) from colorectal cancer (CRC) are initially resectable in only 10-15% of patients (pts). The conversion to resectability following induction chemotherapy is an ...
Published: 2016
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39. Les traitements symptomatiques des douleurs des métastases osseuses vertébrales

Author: Cl. Thonnier, Alain Ravaud, D. Monnin, E. Bussières, Yves Becouarn, F. Lakdja, and A. Lobera
Subjects: Gynecology, medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Advanced stage, medicine, business
Abstract: Les metastases osseuses sont les causes les plus frequentes des douleurs chroniques chez les malades cancereux. Les sites les plus communs sont les vertebres: 70% sont thoraciques, 20% lombo-sacrees, 10% cervicales. Le myelome multiple, les cancers du sein, de la prostate, des poumons representent les causes les plus frequentes de ces localisations osseuses secondaires. La douleur resulte de l’invasion osseuse directe avec activation des nocicepteurs locaux, et/ou de la compression des nerfs, des structures vasculaires et des tissues mous voisins. Les localisations multiples sont frequentes et les douleurs sont donc souvent multifocales. En plus de la douleur et de l’immobilite, les metastases osseuses generent des fractures, une hypercalcemie et des compressions medullaires qu’il faudra traiter. Le schema therapeutique general des douleurs en oncologie inclut les traitements de la ou des causes, le traitement du symptome douloureux, les moyens adjuvants. Cependant des moyens plus specifiques aux douleurs osseuses sont pour certains d’entre eux valides et pour d’autres a mieux preciser. Les facteurs psychologiques, culturels et sociaux sont egalement a prendre en compte. En effet, une prise en charge holistique est habituellement necessaire dans ce contexte pathologique. Le traitement de ces douleurs doit rester etiologique, autant que faire se peut, et fait appel selon le cas a la chimio-hormonotherapie, a la radiotherapie, a la chirurgie. L’approche therapeutique symptomatique se fera en utilisant une strategie conforme a des donnees validees et actualisees.
Published: 1995
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40. The prospective French participitation to IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study in stage III colon cancer: Patients’ characteristics and safety analysis of 3 versus 6 months of adjuvant chemotherapy

Author: Marine Hug de Larauze, Julien Taieb, Olivier Dupuis, Simon Pernot, Karine Le Malicot, Jérôme Dauba, Jérôme Desramé, Laurent Mineur, Jaafar Bennouna, Thierry André, May Mabro, Yves Becouarn, Aimery de Gramont, Franck Bonnetain, Christophe Louvet, Olivier Bouché, Roger Faroux, and Joëlle Egreteau
Subjects: Cancer Research, medicine.medical_specialty, Adjuvant chemotherapy, business.industry, medicine.medical_treatment, Standard treatment, Planned Duration, Surgery, law.invention, Oxaliplatin, 03 medical and health sciences, 0302 clinical medicine, Oncology, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, Clinical endpoint, 030211 gastroenterology & hepatology, Stage (cooking), business, Adjuvant, medicine.drug
Abstract: 633 Background: The IDEA international collaboration was established to prospectively combine/analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the French IDEA study was 2,000 patients. Methods: French IDEA randomized patients with stage III CC between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Oxaliplatin was stopped in case of persistent neuropathy grade ≥2 with fluoropyrimidines continuation for the planned duration. Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to May 2014, 2,023 patients were randomized in 129 French centers either to arm A (n=1009, 49.9%) or to arm B (n=1014, 50.1%). 2012 (99.5%) patients had stage III disease (N1: 75%; N2: 25%) and 11 patients had stage II (n=2) or stage IV disease (n=9). Median age was 64 years (18-85). 89.4% of patients received mFOLFOX6, 10.1% of patients received XELOX, and 0.5% of patients did not receive any study treatment. Overall, 94.1% and 77.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 500 mg/m2 in arm A and 747 mg/m2in arm B. Toxicity profiles depended on the FU backbone with more grade 3/4 neutropenia on mFOLFOX6 (15.0% vs 6.5%) and more grade 3/4 diarrhea (4.7% vs 8.1%) on XELOX. Grade 2/3-4 peripheral neuropathy was less common in arm A than in arm B (23.2/6% vs 37.9/20.4%). Grade 2/3-4 residual neuropathy for patients with a follow-up of at least 3 years (n=811, median follow-up of 3.91 years) was 2.3/0.5% in arm A vs 3.9/ 2.4% in arm B. At 6 months after randomization, mortality rate was 0.7% (n=7) on arm A and 0.5% (n=5) on arm B. Median follow-up is 2.74 years for the whole population. Conclusions: Both mFOLFOX6 and XELOX were safe. Peripheral neuropathy was lower in arm A than in arm B. Clinical trial information: 2009-010384-16.
Published: 2016
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41. Quality indicators for colorectal cancer surgery and care according to patient-, tumor-, and hospitalrelated factors

Author: Simone Mathoulin-Pélissier, Dominique Auby, E. Rullier, Gaëlle Coureau, Anne Jaffre, Elodie Pinon, Geneviève Belleannée, Yves Becouarn, Jean-Louis Renaud-Salis, Unité de Recherche en Epidémiologie Clinique, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Cancéropôle du Grand Sud-Ouest, Centre d'investigation clinique et d'épidémiologie clinique 7 (CIC-EC7), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cancéropôle du Grand Sud-Ouest, Département d'Oncologie médicale, Service de pathologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Cancéropôle du Grand Sud-Ouest, Le Réseau de Cancérologie d'Aquitaine, Agence Nationale Sanitaire et Scientifique en Cancérologie (ANSSC)-Institut national du cancer [Boulogne] (INCA), Registre Général des Cancers de la Gironde, Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED), Département de Médecine, Centre Hospitalier Libourne, Service de Chirurgie Générale (A), CHU Bordeaux [Bordeaux]-Hôpital Saint-André, The authors thank I. Cirilo-Cassaigne for participation in data collection, physicians of the cancer units, the Aquitaine Gastro Association, the Committee of Regional Medical Information for regional data, the 'Ligue contre le cancer' for financial support, Regional Aquitaine Group for Colorectal cancer (GRACCOR), and BMC, Ed.
Subjects: Male, medicine.medical_specialty, Cancer Research, Quality Assurance, Health Care, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymph node evaluation, lcsh:RC254-282, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Internal medicine, Medical practice, medicine, Genetics, Humans, Cancer care, Prospective Studies, Stage (cooking), Digestive System Surgical Procedures, Aged, Quality Indicators, Health Care, Gynecology, Chemotherapy, business.industry, Cancer, Pathology Report, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Hospitals, 3. Good health, Radiation therapy, Cancer care organization, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Observational study, Female, France, Guideline Adherence, Patient Care, business, Colorectal Neoplasms, Research Article
Abstract: Background Colorectal cancer (CRC) care has improved considerably, particularly since the implementation of a quality of care program centered on national evidence-based guidelines. Formal quality assessment is however still needed. The aim of this research was to identify factors associated with practice variation in CRC patient care. Methods CRC patients identified from all cancer centers in South-West France were included. We investigated variations in practices (from diagnosis to surgery), and compliance with recommended guidelines for colon and rectal cancer. We identified factors associated with three colon cancer practice variations potentially linked to better survival: examination of ≥12 lymph nodes (LN), non-use and use of adjuvant chemotherapy for stage II and stage III patients, respectively. Results We included 1,206 patients, 825 (68%) with colon and 381 (32%) with rectal cancer, from 53 hospitals. Compliance was high for resection, pathology report, LN examination, and chemotherapy use for stage III patients. In colon cancer, 26% of stage II patients received adjuvant chemotherapy and 71% of stage III patients. 84% of stage US T3T4 rectal cancer patients received pre-operative radiotherapy. In colon cancer, factors associated with examination of ≥12 LNs were: lower ECOG score, advanced stage and larger hospital volume; factors negatively associated were: left sided tumor location and one hospital district. Use of chemotherapy in stage II patients was associated with younger age, advanced stage, emergency setting and care structure (private and location); whereas under-use in stage III patients was associated with advanced age, presence of comorbidities and private hospitals. Conclusions Although some changes in practices may have occurred since this observational study, these findings represent the most recent report on practices in CRC in this region, and offer a useful methodological approach for assessing quality of care. Guideline compliance was high, although some organizational factors such as hospital size or location influence practice variation. These factors should be the focus of any future guideline implementation.
Published: 2012
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42. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802)

Author: Laurent Bedenne, M. Ychou, L. Mineur, J.F. Seitz, E. Gamelin, Thierry Conroy, Sophie Gourgou-Bourgade, Roland Bugat, Michel Ducreux, Andrew Kramar, Jean-Luc Raoul, O. Bouche, Frédéric Viret, J.-Y. Douillard, Yves Becouarn, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Bolus (medicine), Internal medicine, medicine, Clinical endpoint, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, Hematology, medicine.disease, Confidence interval, 3. Good health, Surgery, Irinotecan, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Adjuvant, medicine.drug
Abstract: Background: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. Patients and methods: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m 2 , 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m 2 bolus, 600 mg/m 2 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m 2 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). Results: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P 0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (Cl) 53% to 66%] and 51 % (95% Cl 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% Cl 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% Cl 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% Cl 59% to 73%) and 61% (95% Cl 53% to 67%) in arms A and B, respectively. Conclusion: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.
Published: 2009

43. Cancer chemotherapy in the elderly: a series of 51 patients aged>70 years

Author: Binh Bui, Alain Ravaud, Yves Becouarn, and René Brunet
Subjects: Pharmacology, Cancer Research, medicine.medical_specialty, Series (stratigraphy), Chemotherapy, Cancer chemotherapy, Karnofsky Performance Status, business.industry, medicine.medical_treatment, Pharmacology toxicology, Cancer, Toxicology, medicine.disease, Surgery, Oncology, Internal medicine, Toxicity, medicine, Pharmacology (medical), business, Grading scale
Abstract: A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were>70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was ≥70% for 40 patients. Malignancies were hematopoietic in 24 cases (47%) and digestive in 15 patients (29%), and 12 subjects (24%) had other types of cancers. The first chemotherapy course was given at the full dose to 23/51 (45.1%) patients. The drug dose was reduced for 28/51 (54.9%) patients, due in 25 cases to the subjects being>70 years old. Neither age, KPS, pretreatment assessment, nor cancer extent was correlated with the modifications made to the first cycle. An overall toxicity of grade 3+4 (WHO grading scale) was noted in 10 subjects (19.6%). Although these elderly patients were probably selected, analysis of their charts did not evidence an increase in chemotherapy toxicity, regardless of the dose they received.
Published: 1991
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44. A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer

Author: Pierre Senesse, J.H. Jacob, S. Thezenas, E. Boucher, Yves Becouarn, C. Montoto-Grillot, Antoine Adenis, L. Cany, F. Cvitkovic, and M. Ychou
Subjects: medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, Phases of clinical research, Irinotecan, Gastroenterology, Folinic acid, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, Chemotherapy, business.industry, Hematology, medicine.disease, Chemotherapy regimen, Surgery, Oxaliplatin, Oncology, Fluorouracil, Camptothecin, business, Colorectal Neoplasms, Febrile neutropenia, medicine.drug
Abstract: Background To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer. Patients and methods In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m2 and irinotecan 180 mg/m2 biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m2 in a 2-h infusion and bolus injection of 5FU 400 mg/m2 on day 1, then a two 400 mg/m2 continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m2 (20 patients) or irinotecan 180 mg/m2 (20 patients). Results Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%. Conclusion The IRINOX arm has a manageable toxicity and is active.
Published: 2007

45. 2294 Growth modulation index (GMI) to assess salvage chemotherapy benefit after FOLFIRINOX progression in metastatic pancreatic adenocarcinoma

Author: Mohamed Hebbar, Nicolas Penel, Stéphanie Clisant, Vincent Hautefeuille, F. El Hajbi, C. Desauw, A. Ducoulombier, Antoine Adenis, O. Bouche, Jaafar Bennouna, Aurélie Parzy, J. Quintin, Yves Becouarn, M. Desjardin, and Bruno Chauffert
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, FOLFIRINOX, Internal medicine, Salvage treatment, Modulation index, Medicine, Metastatic Pancreatic Adenocarcinoma, business
Published: 2015
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46. An investigation of the role of irinotecan and oxaliplatin in liver toxicity during first-line neoadjuvant chemotherapy

Author: Gregoire Desolneux, Dominique Béchade, Benjamin Bonhomme, Yves Becouarn, Marie Desjardin, Serge Evrard, Jeremy Vara, Marianne Fonck, Isabelle Soubeyran, and Véronique Brouste
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Liver toxicity, business.industry, First line, medicine.medical_treatment, medicine.disease, Oxaliplatin, Irinotecan, Increased risk, Internal medicine, Toxicity, medicine, Steatohepatitis, business, medicine.drug
Abstract: 689 Background: Neoadjuvant chemotherapy (CT) have been associated with an increased risk of surgery for colorectal liver metastases (CRLM). Irinotecan (IRI) is claimed to induce CT-associated steatohepatitis (CASH) and oxaliplatin (OX) to induce sinusoidal obstruction (SOS). Imputability is sometimes difficult to establish and the impact on postoperative complications is unclear. The objective of this study is to investigate the impact of IRI and OX on induced liver toxicity, and to study the effects of toxicity on surgical outcomes. Methods: Patients (Pts) who received only one line of CT before resection of CRLM were retrospectively included. CASH and SOS were described according to Kleiner and Rubbia-Brandt classifications respectively. Associations were sought between CASH or SOS and various patient and treatment factors, and between patient and treatment factors and the occurrence of post-operative complications grade 3 or over. Results: Among 379 pts operated on for CRLM from 2003 to 2013, 223 were eligible for inclusion; 57 were excluded as there was no healthy hepatic parenchyma to be analyzed. Median age was 64 y [34-88], BMI ≥25 kg/m² for 52%, 8% had diabetes, and 28% had a dyslipidemia. CRLM were synchronous in 76.5%. 65 (39.2%) received Folfox, 95 (57.2%) Folfiri and 6 (3.6%) Folfirinox. Bevacizumab, cetuximab and panitumumab were given in 71 (42.8%), 30 (17.5%), 4 (2.4%) respectively. Extra-hepatic resections were performed in 78 pts (47%). 90-day mortality was 1.8% and 31 pts encountered complications more severe than 3A. Histological hepatoxicity was established for 82 pts (49%) including 33 (19.9%) with grade 2 or 3 SOS and 22 (13%) with CASH. No significant associations were identified between SOS and OX, nor CASH and IRI. BMI ≥ 25 kg/m² was correlated with an increased risk of CASH. Only septic extra-hepatic surgeries were correlated with the prediction of postoperative complications. Conclusions: In this selected series, preoperative CT was not associated to liver toxicity. The presence of histological lesions did not worsen post-operative outcomes. BMI and extra-hepatic surgery were the only co-factors correlated with CASH and post-operative complications respectively.
Published: 2015
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47. Surgical treatment of liver metastases by radiofrequency ablation, resection, or in combination

Author: Simone Mathoulin-Pélissier, V. Picot, Yves Becouarn, Serge Evrard, Marianne Fonck, and René Brunet
Subjects: Adult, Male, medicine.medical_specialty, Colorectal cancer, Radiofrequency ablation, medicine.medical_treatment, Computed tomography, Pilot Projects, Resection, law.invention, Lesion, Postoperative Complications, law, medicine, Humans, Prospective Studies, Surgical treatment, Aged, Aged, 80 and over, Intention-to-treat analysis, medicine.diagnostic_test, business.industry, Liver Neoplasms, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Surgery, Treatment Outcome, Oncology, Catheter Ablation, Female, Radiology, Hepatectomy, medicine.symptom, Neoplasm Recurrence, Local, business, Colorectal Neoplasms
Abstract: Aims. Radiofrequency ablation (RFA) has a role in the treatment of unresectable liver metastases either percutaneously or in open surgery. The aim of this study was to determine the feasibility and value using RFA, resection or in combination to cure liver metastases of colorectal or other origin. Methods. Fifty-two consecutive patients were operated on with the intention to treat their liver metastases using both techniques of RFA and resection in the same curative intent. A CT scan was performed 2 months postoperatively and then every 4 months. Results. Fifty patients with 137 metastases could be treated: 55 lesions were resected and 82 were ablated. Curative treatment of 13 patients could only be achieved by using RFA combined with resection. Morbidity was 16% and local treatment proved insufficient in three cases. Estimated 1-year survival probabilities were, respectively, 0.85 in the colorectal group and 0.80 in the non-colorectal group. Conclusions. RFA increased resectability of liver metastases and reduced the morbidity. Respective indications of both techniques were complementary and depend on the size and the topography of the lesion to be treated.
Published: 2004

48. 6011 ORAL Unresectable Colorectal Liver Metastases Treated by Intraoperative Radiofrequency Ablation With or Without Resection: the ARF2003 Study

Author: René Brunet, Serge Evrard, Michel Rivoire, E. Lermite, J.-P. Arnaud, M. Fonck, Carine Bellera, Caroline Lalet, Simone Mathoulin-Pélissier, and Yves Becouarn
Subjects: Cancer Research, medicine.medical_specialty, Oncology, business.industry, Radiofrequency ablation, law, General surgery, medicine, Radiology, business, Resection, law.invention
Published: 2011
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49. 45. Colorectal peritoneal carcinomatosis treated by completed surgery + systemic chemotherapy: Futility of HIPEC?

Author: C. Maziere, Serge Evrard, J. Vara, Gregoire Desolneux, Yves Becouarn, Marianne Fonck, and Dominique Béchade
Subjects: medicine.medical_specialty, Oncology, Systemic chemotherapy, business.industry, medicine, Surgery, General Medicine, business, Peritoneal carcinomatosis
Published: 2014
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50. Métastases hépatiques coloroectales initialement non résécables : vers une désescalade chirurgicale ? Le concept CARe

Author: Yves Becouarn, Serge Evrard, S. Staettner, Jeremy Vara, Graeme J. Poston, Gregoire Desolneux, Peter Kissmeyer-Nielsen, Marianne Fonck, and Yuman Fong
Subjects: Surgery
Abstract: Introduction Associer ablathermie peroperatoire (APO) et resection dans la chirurgie des metastases hepatiques colorectales (MHCR) non resecables. Les objectifs etaient d’evaluer : survie globale (SG), sans recidive locale (SSRL), sans recidive hepatique (SSRH) et sans progression (SSP) a 3 ans. Les complications postoperatoires et facteurs pronostiques de survie etaient etudies. Patients et methodes Quatre centres partageant le meme paradigme ont mis en commun leurs databases de MHCR non resecables traitees par resections plus APO. Resultats De 2001 a 2011, 288 patients ont beneficie de cette approche : 232 (81 %) ont recu une chimiotherapie preoperatoire, 210 avaient des MHCR synchrones (73,4 %) bilaterales chez 255 patients (88,5 %). Le nombre median de MHCR etait 5 [2–21], resequees 2 [1–19] et ablatees 2 [1–12]. Les tailles moyennes etaient : 15 mm pour resection et 11 mm pour ablation. La mortalite etait a 1 %, la morbidite a 34,7 %. Le suivi moyen etait 3,17 ans. La SG mediane etait 3,33 ans [95 % CI (3,08- 4,17)]. La SSRL etait respectivement a 1, 2 et 3 ans : 89,4 %, 85,5 % et 81,2 %. La mediane de SSRH etait de14 mois [95 % CI11–18], la SSP mediane de 9 mois [95 % CI 8–11]. En multivarie, la survenue d’une complication etait un facteur pronostique independant avec une diminution des taux de survie a 3 ans : SG (HR 1,93, p = 0,002), SSRL (HR 1,396, p = 0,035) et SSP (HR 1,399, p = 0,022). Conclusion L’APO combinee a la resection est une alternative a l’hepatectomie extensive.
Published: 2014
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