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1. Management of neuroendocrine neoplasms: conformity with guidelines in and outside a center of excellence

Author

Carole Morin, Keo-Morakort Benedetto, Agathe Deville, Laurent Milot, Aurélie Theillaumas, Valérie Hervieu, Mathieu Pioche, Gilles Poncet, Julien Forestier, Laurent François, Francoise Borson-Chazot, Mustapha Adham, Catherine Lombard-Bohas, and Thomas Walter

Subjects
neuroendocrine neoplasm, enets center of excellence, diagnostic management, conformity to clinical guidelines, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Purpose: To improve neuroendocrine neoplasm (NEN) management, the European Neuroendocrine Tumor Society (ENETS) recognised 62 Centers of Excellence (CoE). This retrospective study compares conformity of patients’ initial management within vs outside an ENETS CoE with clinical practice guidelines (CPGs). Methods: Patients diagnosed with a NEN between August 2018 and July 2020 and presented in the Lyon-CoE Multidisciplinary Tumour Board (MDT) were included. Factors potentially associated with the conformity of initial management (work-up and first treatment) to CPG underwent univariate and multivariate analyses. Results: Among the 615 included patients, 170 (27.6%) were initially managed in the CoE and 445 (72.4%) were only presented at the CoE-MDT. Patients in the CoE group more often had intestinal or pancreatic primaries, metastatic disease (61.8% vs 33%), hereditary syndrome, and a functioning tumour. Work-up conformity was 37.1% in the CoE (vs 29.9%, P = 0.09); this was 95.8% for the first treatment (vs 88.7%, P = 0.01). After multivariate analysis, CPG conformity was significantly higher for patients managed in the CoE, for younger patients, for those having a grade 1–2 tumour, and a genetic syndrome. Pancreatic and small intestinal (SI) NET surgeries performed in the CoE had a higher splenic preservation rate during left pancreatectomy, better detection of multiple tumours in SI surgeries, and higher number of resected lymph nodes. Conclusions: Given the widespread observance of CPG, not all patients require management in the CoE. Referral should be considered for more complex cases such as metastatic diseases, G2 tumours, or carcinoid syndromes. Finally, we should encourage the centralization of NET surgery.

Published
2022
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2. Metformin and everolimus in neuroendocrine tumours: A synergic effect?

Author

Julien Forestier, Philip Robinson, Catherine Lombard-Bohas, Gérald Raverot, Laurent Milot, Annie Lemelin, Françoise Borson-Chazot, Lucia Hue-Fontaine, Thomas Walter, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Délégation à la recherche clinique et à l'innovation [CHU Dijon] (DRCI), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
Male, Oncology, medicine.medical_specialty, Lung Neoplasms, endocrine system diseases, [SDV]Life Sciences [q-bio], Population, Antineoplastic Agents, Neuroendocrine tumors, Digestive System Neoplasms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Clinical endpoint, Humans, Hypoglycemic Agents, Everolimus, Prospective cohort study, education, Aged, education.field_of_study, Univariate analysis, Hepatology, business.industry, Gastroenterology, Drug Synergism, Middle Aged, medicine.disease, Metformin, Progression-Free Survival, 3. Good health, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

To explore potential synergy in effectiveness between metformin and everolimus, 2 inhibitors of the mTOR pathway, for neuroendocrine tumours (NET).A cohort of patients with advanced gastroenteropancreatic or lung NETs treated by everolimus were stratified in to those without diabetes, those with diabetes and without metformin, and those with diabetes with metformin. The primary endpoint was the median progression-free survival (PFS).A total of 213 patients were included, 165 of which were non-diabetic; among diabetic patients, 19 were treated with metformin and 29 with others anti-diabetic drugs. No significant difference in median PFS [95%CI] was found between the three groups: 10.05 months [8.27;11.83] for non-diabetic patients, 15.24 [19.88;49.43] for diabetic w/metformin, and 9.03 months [4.01;14.06] for diabetic w/o metformin group. In univariate analysis, factors significantly associated with longer PFS was a functioning NET, a number of metastatic sites3, the absence of lung metastasis, and an uptake on Octreoscan®, but not the absence of metformin use; only uptake on Octreoscan® remained significant in multivariate analysis.In contrast with the literature, we did not find a synergy between everolimus and metformin in NET. Prospective studies are underway to improve the comprehension of the potential synergy regarding population and tumour type.

Published
2020
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3. Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms

Author

Julien Forestier, Thomas Walter, Philippe Ruszniewski, Mathieu Pioche, Ingrid Millot, Valérie Hervieu, Fabien Subtil, Pierre-Jean Valette, Louis de Mestier, Julie Perinel, Catherine Lombard-Bohas, Servane Gay-Chevallier, and Mustapha Adham

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Endocrinology, Diabetes and Metabolism, Oncological surgery, 030209 endocrinology & metabolism, Neuroendocrine tumors, Gastroenterology, Disease-Free Survival, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Duodenal Neoplasms, Internal medicine, medicine, Humans, In patient, Survival rate, Duodenal Neoplasm, Aged, Retrospective Studies, Aged, 80 and over, Univariate analysis, medicine.diagnostic_test, Endocrine and Autonomic Systems, business.industry, Middle Aged, medicine.disease, Endoscopy, Neuroendocrine Tumors, Outcome and Process Assessment, Health Care, Female, business, Follow-Up Studies
Abstract

Introduction: The characteristics, prognostic factors, and management of duodenal neuroendocrine neoplasms (dNEN) are ill-defined, given their rarity. Whether nonsurgical management might be appropriate for patients with nonmetastatic dNEN and a good prognosis, as is the case for pancreatic NEN (pNEN), is unknown. We aimed to describe the management and prognosis of nonmetastatic dNEN patients. Methods: All consecutive patients with nonmetastatic dNEN managed between 1981 and 2018 in 2 expert centers were included. Recurrence-free survival (RFS) and factors associated with recurrence were estimated. Results: A total of 145 patients with dNEN were included. Twenty-eight patients with sporadic, nonfunctioning, small (median 7 mm) dNEN underwent endoscopic resection, with a 5-year RFS rate of 89.4%. Local recurrence occurred in 2 patients, who underwent surgery with no new events. The 5-year RFS rate was 87.9% in patients who underwent surgery. Upon univariate analysis, age, size, Ki67 index, and lymph node involvement (LN+) were significantly associated with worse RFS for all dNEN treated (endoscopy/surgery); multivariate analysis found that age, size, and LN+ were associated with worse RFS. Conclusion: Selected nonmetastatic dNEN had a favorable outcome, and a less invasive therapeutic strategy appeared more suitable than oncological surgery.

Published
2020
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4. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer

Author

Violaine Randrian, Simon Pernot, Karine Le Malicot, Vittorio Catena, Isabelle Baumgaertner, Vania Tacher, Julien Forestier, Vincent Hautefeuille, Claire Tabouret-Viaud, Alice Gagnaire, Emmanuel Mitry, Boris Guiu, Thomas Aparicio, Denis Smith, Anthony Dhomps, Jean-Pierre Tasu, Rémy Perdrisot, Julien Edeline, Claude Capron, Catherine Cheze-Le Rest, Jean-François Emile, Pierre Laurent-Puig, Theodora Bejan-Angoulvant, Harry Sokol, Come Lepage, Julien Taieb, David Tougeron, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Bergonié [Bordeaux], UNICANCER, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, 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), Fédération Francophone de Cancérologie Digestive (FFCD), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Université de Genève = University of Geneva (UNIGE), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Universitaire [Rennes], CRLCC Eugène Marquis (CRLCC), Hôpital Ambroise Paré [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This study was supported in part by Roche and Biocompatibles UK Ltd, a wholly owned subsidiary of Boston Scientific Corporation. Fédération Francophone de Cancérologie Digestive (FFCD) is funding the bio-bank and molecular analysis.

Subjects
Hepatology, Rectal Neoplasms, Selective internal radiation therapy, Liver Neoplasms, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immune checkpoint inhibitor, Antibodies, Monoclonal, Humanized, Colorectal cancer, Bevacizumab, Liver metastases, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Humans, Sirtuins, Prospective Studies, Colorectal Neoplasms
Abstract

International audience; Abstract The cellular prion protein PrP C partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrP C and CAV1 across cancer. Using cell-based assays, we show that PrP C regulates the expression of and interacts with CAV1. PrP C additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrP C -dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrP C interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrP C -dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrP C axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.

Published
2022
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5. Elderly Patients with Metastatic Neuroendocrine Tumors Are Undertreated and Have Shorter Survival: The LyREMeNET Study

Author

Elisabeth Castel-Kremer, Philip Robinson, Catherine Lombard-Bohas, Valérie Hervieu, Marianne Lorcet, Julien Forestier, Annie Lemelin, Thomas Walter, Aurélie Theillaumas, Florent Boutitie, Delphine Maucort-Boulch, and Antoine Duclos

Subjects
Adult, Male, medicine.medical_specialty, Health Services for the Aged, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, 030209 endocrinology & metabolism, Neuroendocrine tumors, Health Services Misuse, 030218 nuclear medicine & medical imaging, Targeted therapy, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Internal medicine, Humans, Medicine, Age of Onset, Neoplasm Metastasis, Practice Patterns, Physicians', education, Aged, Retrospective Studies, Cause of death, Aged, 80 and over, Chemotherapy, education.field_of_study, Endocrine and Autonomic Systems, business.industry, Incidence (epidemiology), Age Factors, Cancer, Middle Aged, Patient Acceptance of Health Care, Prognosis, medicine.disease, Survival Analysis, Neuroendocrine Tumors, Radionuclide therapy, Female, France, business
Abstract

Introduction: The incidence of neuroendocrine tumors (NETs) is rising, especially in elderly patients. The elderly cancer population presents considerable challenges, yet little is known about the characteristics, treatment patterns, and outcomes of metastatic NET (mNET) patients. Methods: The Lyon Real-life Evidence in Metastatic NeuroEndocrine Tumors study (LyREMeNET, NCT03863106) included consecutive mNET patients, diagnosed between January 1990 and December 2017. The exclusion criteria were nonmetastatic NET, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-nonneuroendocrine neoplasms. We aimed to compare patients ≥70 years old to patients Results: A total of 866 patients were included, 198 (23%) were ≥70 years old. There was no significant difference in characteristics except that elderly patients had synchronous metastasis more frequently. Elderly patients received significantly fewer treatments (median of 2.0 vs. 3.0 lines, respectively, p < 0.0001), were significantly less frequently treated by chemotherapy (32 vs. 54%), targeted therapy (16 vs. 30%), peptide receptor radionuclide therapy (5 vs. 16%), and they underwent significantly less frequently locoregional intervention. Median overall survival was significantly shorter in elderly patients (5.2 vs. 9.6 years). The most frequent cause of death was related to disease progression (71%). Multivariate analysis found that, after adjustment for tumor location, tumor grade, and number of metastatic sites, age remained significantly associated with overall survival (HR 1.66, 95% CI 1.26–2.18), indicating a poorer survival in patients ≥70 years old in comparison with younger patients (p = 0.0003). Conclusion: Patients ≥70 years old have a worse survival, die frequently from their disease, and are undertreated compared to younger patients.

Published
2019
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6. Characterization, Prognosis, and Treatment of Patients With Metastatic Lung Carcinoid Tumors

Author

Michel Ducreux, Amandine Berdelou, Patrick Robelin, Valérie Hervieu, Pierre-Jean Valette, Sophie Leboulleux, Eric Baudin, Jean-Yves Scoazec, Julien Hadoux, David Planchard, Catherine Lombard-Bohas, Thomas Walter, Julien Forestier, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'oncologie médicale, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut Gustave Roussy (IGR), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], Carcinoid tumors, Carcinoid Tumor, Neuroendocrine tumors, Scintigraphy, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm Metastasis, Aged, Randomized Controlled Trials as Topic, Retrospective Studies, Aged, 80 and over, Performance status, medicine.diagnostic_test, business.industry, Hazard ratio, Middle Aged, Prognosis, medicine.disease, 3. Good health, Oxaliplatin, Survival Rate, 030104 developmental biology, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Radionuclide therapy, Female, business, medicine.drug
Abstract

Introduction Metastatic lung carcinoids (MLCs) remain poorly characterized and no prognostic stratification exists. Methods We conducted a retrospective study including patients with MLCs in two European expert centers. The aims were to characterize these cases and to identify prognostic factors of survival and effectiveness of their treatments. Results A total of 162 patients with MLC were included: 50% were women, and the median age was 61 years. Half of the patients had synchronous metastases, mainly located in the liver (75%), bone (42%), and lung (25%). According to WHO classification, MLCs were typical (28%), atypical (60%), or unspecified (12%). A functioning syndrome was observed in 43% of cases and an uptake at somatostatin receptor scintigraphy in 76% of cases. The 5-year overall survival rate was 60% and at 10 years this was 25%. In multivariate analysis, Eastern Cooperative Oncology Group performance status of 0-1 (hazard ratio [HR]: 5.81, 95% confidence interval [CI]: 2.10–16.11), uptake on SRS (HR: 0.38, 95% CI: 0.22–0.66), low serum chromogranin A (HR: 2.27, 95% CI: 1.36–3.81), and typical carcinoid (HR: 1.87, 95% CI: 1.26–2.78) were associated with better survival. According to Response Evaluation Criteria in Solid Tumors version 1.0, the highest objective response rates were obtained after radiofrequency ablation of metastases (86%), liver embolization (56%), peptide receptor radionuclide therapy (27%), and oxaliplatin-based chemotherapy (18%). Conclusions MLCs are characterized by a high frequency of atypical carcinoids, functioning syndrome, and liver/bone metastases. WHO classification, performance status, somatostatin receptor scintigraphy, and chromogranin A were associated with longer survival. Partial response was more frequent with locoregional therapies, peptide receptor radionuclide therapy, or oxaliplatin-based chemotherapy.

Published
2019
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7. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author

Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Published
2020
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8. Unifocal versus multiple ileal neuroendocrine tumors location: an embryological origin

Author

Thomas Walter, Gilles Poncet, Colette Roche, Ingrid Millot, Valérie Hervieu, Maroin Kalifi, Laurent Milot, Arnaud Pasquer, Julien Forestier, Catherine Lombard-Bohas, Benjamin Gibert, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Ileum, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neuroendocrine tumors, 030218 nuclear medicine & medical imaging, Resection, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ileocecal valve, 0302 clinical medicine, Endocrinology, medicine.artery, Internal medicine, medicine, Humans, Superior mesenteric artery, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Endocrine and Autonomic Systems, business.industry, Middle Aged, Neoplasms, Germ Cell and Embryonal, SMA, medicine.disease, Ileal Neoplasms, Neuroendocrine Tumors, medicine.anatomical_structure, Potential difference, Female, Nuclear medicine, business
Abstract

Introduction: Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET. Patients and Methods: Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least 1 non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40 cm from the ileocecal valve), and unifocal ones on the right side. Results: Ninety-four patients were included, 6 with unifocal jejunal-NET located 35 cm (range, 10–60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2–95), within a median small bowel segment of 105 cm (10–240). The median length between the proximal tumor and the DJA was 428 cm (300–635) and 540 cm (350–725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577 cm (305–820) from the DJA (p < 0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p < 0.001). Conclusion: Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.

Published
2020
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9. Endoscopic management of 345 small rectal neuroendocrine tumours: A national study from the French group of endocrine tumours (GTE)

Author

Christine Do Cao, Romain Coriat, Patricia Nicolli, Elise Coffin, Guillaume Roquin, Thomas Walter, Jeanne Ramos, Thierry Lecomte, Vincent Lepiliez, Sophie Dominguez, Paul Girot, Eric Terrebonne, Valérie Hervieu, Mathieu Pioche, Caroline Fine, Louis de Mestier, Guillaume Cadiot, Vincent Hautefeuille, Fritz-Line V Céphise, Julien Forestier, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Institut Cochin (IC 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), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital privé Jean Mermoz, CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Formation en Santé (IFsanté), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Application des ultrasons à la thérapie (LabTAU), Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Salvy-Córdoba, Nathalie, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université catholique de Lille - Institut de formation en santé (UCL IFS), Université catholique de Lille (UCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Reoperation, Transanal Endoscopic Microsurgery, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endoscopic management, Resection, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Endocrine system, Humans, Endoscopic resection, Neoplasm Invasiveness, Pathological, Neoplasm Staging, Retrospective Studies, Surgeons, medicine.diagnostic_test, business.industry, Rectal Neoplasms, Gastroenterology, Endoscopy, Original Articles, Middle Aged, 3. Good health, Neuroendocrine Tumors, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, National study, 030211 gastroenterology & hepatology, Female, Radiology, Rectal, neuroendocrine tumours, France, Neoplasm Grading, Neoplasm Recurrence, Local, business, management, Procedures and Techniques Utilization, Follow-Up Studies
Abstract

International audience; INTRODUCTION:Small rectal neuroendocrine tumours are good candidates for endoscopic resection provided that complete pathological resection (R0) is obtained and their risk of metastatic progression is low. We conducted a large multicentre nationwide study to evaluate the outcomes of the management of non-metastatic rectal neuroendocrine tumours ≤2 cm diagnosed endoscopically.PATIENTS AND METHODS:The medical records, the endoscopic and pathological findings of patients with non-metastatic rectal neuroendocrine tumours ≤2 cm managed from January 2000-June 2018 in 16 French hospitals, were retrospectively analysed. The primary objective was to describe the proportion of R0 endoscopic resections.RESULTS:A total of 329 patients with 345 rectal neuroendocrine tumours were included, 330 (96%) tumours were managed by local treatments: 287 by endoscopy only and 43 by endoscopy followed by transanal endoscopic microsurgery. The final endoscopic R0 rate was 134/345 (39%), which improved from the first endoscopy (54/225, 24%), to the second (60/100, 60%) and the third endoscopy (20/26, 77%). R0 was associated with endoscopic technique (90% for advanced techniques, 40% for mucosectomy and 17% for polypectomy), but not with tumour or patient characteristics. Twenty patients had metastatic disease, which was associated with tumour size ≥10 mm (odds ratio: 9.1, 95% confidence interval (3.5-23.5)), tumour grade G2-G3 (odds ratio: 4.2, (1.5-11.7)), the presence of muscular (odds ratio: ∞, (11.9-∞)) and lymphovascular invasion (odds ratio: 57.2, (5.6-578.9)).CONCLUSIONS:The resection of small rectal neuroendocrine tumours often requires multiple procedures. Training of endoscopists is necessary in order to better recognise these tumours and to perform the appropriate resection technique.

Published
2019
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11. Type 1 serrated polyposis represents a predominantly female disease with a high prevalence of dysplastic serrated adenomas, without germline mutation in MUTYH, APC , and PTEN genes

Author

Valérie Hervieu, Marie-Odile Joly, Thomas Walter, Jean-Christophe Saurin, Marco Petronio, Stéphane Pinson, and Julien Forestier

Subjects
medicine.medical_specialty, business.industry, Colorectal cancer, medicine.medical_treatment, Genetic counseling, Gastroenterology, Original Articles, medicine.disease, Germline, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Oncology, Hyperplastic Polyp, Dysplasia, MUTYH, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, Colectomy
Abstract

The aim of this article is to clarify the epidemiologic, clinical, endoscopic, biological and genetic characteristics of type 1 serrated polyposis patients.Consecutive patients responding to the WHO definition of type 1 serrated polyposis in one reference center for polyposis patients accepted genetic counseling. Detailed data on previous endoscopies, histology, and life habits were recorded, after informed consent, germline analysis of MUTYH, APC, and PTEN germline mutations. Molecular biology was tested on available fixed tissue from different lesion types.We included 29 patients (mean age 53.5 years, 21 women (72.4%)), four with a personal history of colorectal cancer (CRC), with a mean of 11.6 SSAs, with associated hyperplastic polyps in 93.1% and adenomas in 82.8%. SSAs showed no dysplasia in 46.9% of lesions (three of 29 patients), LGD in 51.9% (22/29 patients), and HGD in 1.2% (four of 29 patients). Dysplasia was more frequent in proximal SSAs and in women. Colectomy 15 patients (51.7%), upper digestive neoplasms: eight patients (27.5%); smokers: 24 patients (82.8%); family history of CRC: 16 patients (55.2%). Biology: MSI-H phenotype in one SSA, V600E BRAF mutation in 95% of SSAs; MGMT hypermethylation in three of 17 SSAs. No germline mutation was detected in MYH, APC or PTEN genes.Type 1 serrated polyposis corresponds to a majority of women, with a high prevalence of smokers, a high prevalence of dysplastic serrated adenomas, particularly in females, without identified germline mutation in targeted predisposing genes.

Published
2016
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12. Gastric neuroendocrine tumors display deep invasive features, with amorphous pit and irregular vascular pattern, using narrow-band imaging and magnification

Author

Pierre-Marie Lavrut, Thomas Walter, Adrien Choné, Jean-Christophe Saurin, Jérôme Rivory, Julien Forestier, and Mathieu Pioche

Subjects
Male, medicine.medical_specialty, Endoscopic Mucosal Resection, Magnification, Endoscopic mucosal resection, Neuroendocrine tumors, 03 medical and health sciences, Narrow Band Imaging, 0302 clinical medicine, Stomach Neoplasms, Gastroscopy, medicine, Humans, Ulcer, Aged, Narrow-band imaging, business.industry, Gastroenterology, medicine.disease, Amorphous solid, Capillaries, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Radiology, business
Published
2018

13. Gemcitabine and oxaliplatin or alkylating agents for neuroendocrine tumors: Comparison of efficacy and search for predictive factors guiding treatment choice

Author

Julien Forestier, Jean-Yves Scoazec, Cécile Vercherat, Valérie Hervieu, Thomas Walter, Marie-Odile Joly, Catherine Lombard-Bohas, and Anne-Sophie Dussol

Subjects
Oncology, Cancer Research, medicine.medical_specialty, education.field_of_study, Temozolomide, business.industry, Dacarbazine, Population, Cancer, GemOx, Pharmacology, medicine.disease, Chemotherapy regimen, Gemcitabine, Oxaliplatin, Internal medicine, medicine, business, education, medicine.drug
Abstract

BACKGROUND The alkylating agents (ALKYs) streptozotocin, dacarbazine, and temozolomide currently are the main drugs used in systemic chemotherapy for neuroendocrine tumors (NETs). The promising activity shown by gemcitabine and oxaliplatin (GEMOX) in previous studies prompted this study 1) to confirm the use of GEMOX in a larger population of NET patients, 2) to compare its efficacy with that of ALKYs, and 3) to explore whether the O6-methylguanine-DNA methyltransferase (MGMT) status could help in selecting the chemotherapy regimen. METHODS One hundred four patients with metastatic NETs (37 pancreatic NETs, 33 gastrointestinal NETs, 23 bronchial NETs, and 11 NETs of other/unknown origin) were treated with GEMOX between 2004 and 2014. Among these patients, 63 also received ALKYs. MGMT promoter gene methylation was assessed via pyrosequencing in 42 patients. RESULTS Patients received a median of 6 courses of GEMOX. Twenty-four (23%) had an objective response (OR). The median progression-free survival (PFS) and overall survival were 7.8 and 31.6 months, respectively. In the 63 patients treated with both ALKYs and GEMOX, the ORs (22% and 22%) and the PFSs (7.5 and 7.3 months) were similar. The response was concordant in 53% of the patients. Promoter gene methylation of MGMT was associated with better outcomes with ALKYs (P = .03 for OR and P = .04 for PFS) but not GEMOX. CONCLUSIONS GEMOX is effective against NETs; its activity is comparable to that of ALKYs, and it is not influenced by the MGMT status. Our data suggest that GEMOX might be preferred for patients with unmethylated MGMT tumors. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

Published
2015
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14. Surgical Management of Small Bowel Neuroendocrine Tumors: Specific Requirements and Their Impact on Staging and Prognosis

Author

Arnaud Pasquer, Thomas Walter, Catherine Lombard-Bohas, Valérie Hervieu, Gilles Poncet, Jean-Yves Scoazec, and Julien Forestier

Subjects
Adult, Male, medicine.medical_specialty, Adenocarcinoma, Neuroendocrine tumors, Palpation, Surgical oncology, Intestinal Neoplasms, Intestine, Small, medicine, Humans, Neoplasm Metastasis, Lymph node, Survival rate, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Disease Management, Perioperative, Middle Aged, Prognosis, medicine.disease, Primary tumor, Surgery, Survival Rate, Neuroendocrine Tumors, medicine.anatomical_structure, Oncology, Lymph Node Excision, Female, Radiology, Neoplasm Grading, Neoplasm Recurrence, Local, business, Carcinoid syndrome, Follow-Up Studies
Abstract

Small bowel neuroendocrine tumors (SB-NETs) are characterized by two main features: they usually are metastatic at diagnosis and multiple in 30 % of cases. As such, SB-NETs require specific surgical management. This retrospective study examined local recurrence, survival, and prognosis of SB-NETs after adapted surgery. All consecutive patients with SB-NETs who underwent resection of at least one primary tumor between 1 January 2000 and 1 January 2013 were analyzed. The preoperative morphologic workup, histologic classification, and metastatic lymph node (LN) ratio (LNs involved/removed) were recorded. The study enrolled 107 patients, 35 (33 %) of whom had multiple SB-NETs (range 1–44; mean 3.1). Preoperative imaging and perioperative surgical examination missed 61 and 33 % of SB-NETs, respectively, in contrast to pathologic examination. Of the 107 patients, 43 % had carcinoid syndrome, 70 % had metastatic disease, and 90 % had LN involvement. The median number of LNs retrieved was 12 (range 1–69). The LN ratio (LNs involved/removed) was 0.25. The highest tumoral grades were G1 (in 61 % of patients) and G2 (in 37 % of patients). Of the 107 patients, 13 (12 %) had local LN recurrence. The rate of LN recurrence-free survival at 5 years was 88 %. The median overall survival (OS) time was 128 months (range 91–165 months). In the multivariate analysis, high chromogranin A (CgA) levels and peritoneal carcinomatosis were significantly associated with shorter OS. Systematic palpation of the entire small bowel detects more multiple NETs than preoperative imaging. Systematic surgery with extensive LN resection is associated with low local recurrence. High CgA levels and carcinomatosis are linked with shorter survival.

Published
2015
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15. Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

Author

Emmanuelle Graillot, Mustapha Adham, Thomas Walter, Valérie Hervieu, Philip Robinson, Julien Forestier, Jean-Yves Scoazec, Pascal Rousset, Margaux Foulfoin, and Catherine Lombard-Bohas

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Liver tumor, Indoles, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Antineoplastic Agents, Bone Neoplasms, Guidelines as Topic, Kaplan-Meier Estimate, Neuroendocrine tumors, Gastroenterology, Metastasis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Sunitinib, Humans, Pyrroles, Everolimus, Young adult, Societies, Medical, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, business.industry, Liver Neoplasms, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Pancreatic Neoplasms, Neuroendocrine Tumors, Oncology, 030220 oncology & carcinogenesis, Female, business, Progressive disease, medicine.drug
Abstract

The choice of first-line treatment for metastatic pancreatic neuroendocrine tumors (mP-NET) is mainly based on prognostic factors. ENETS-2016 guidelines stratified treatment according to 3 groups: Group 1, patients in whom all lesions could be removed; Group 2, patients with Ki67 10% or significant tumor burden or progressive disease, for whom a systemic chemotherapy is proposed. This retrospective study aimed to determine patient distribution, characteristics and outcome among these 3 groups. Patients with mP-NET diagnosis from 2004 to 2016 were categorized into the three groups. Prognosis was calculated using the Kaplan–Meier method. All treatments were recorded, and consistency with ENETS guidelines was explored. 104 patients were analyzed: 64% synchronous mP-NET, 80% grade 2 tumors and median overall survival (OS) of 104 (95% CI: 65–143) months. There were 15 patients in ENETS Group 1, 16 in Group 2 and 73 in Group 3. Median OS was not reached in Groups 1 and 2 and was 64 months (35–93) in Group 3. High liver tumor volume, high-grade tumor and progressive disease were associated with worse OS in multivariate analysis. The first-line treatment was in accordance with guidelines in 82%. 77% percent of deceased patients received less than 4 lines of treatment. Most patients are in Group 3 and do not receive all available treatments. Thus, trials are warranted to improve first-line chemotherapy. Alternative treatments may be considered for less aggressive disease.

Published
2016

16. Lymphadenectomy during Small Bowel Neuroendocrine Tumor Surgery: The Concept of Skip Metastases

Author

Arnaud Pasquer, Valérie Hervieu, Thomas Walter, Gilles Poncet, Pascal Rousset, Julien Forestier, and Catherine Lombard-Bohas

Subjects
Oncology, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Neuroendocrine tumors, Complete resection, 03 medical and health sciences, 0302 clinical medicine, Mesenteric Veins, Surgical oncology, Internal medicine, Intestine, Small, medicine, Humans, Prospective Studies, Lymph node, Pancreas, Aged, Aged, 80 and over, Jejunal Neoplasms, business.industry, Middle Aged, medicine.disease, Primary tumor, Mesenteric Arteries, Ileal Neoplasms, Neuroendocrine Tumors, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Lymph Node Excision, 030211 gastroenterology & hepatology, Surgery, Lymphadenectomy, Tumor surgery, Female, Radiology, Lymph Nodes, business
Abstract

More than half of small bowel neuroendocrine tumors (SB-NETs) are metastatic at diagnosis, but complete resection of the primary tumor and lymph node (LN) is recommended by most authors. Our aim was to describe the pattern of involved LN after an extensive LN resection.Between July 2013 and December 2015, all consecutive patients who underwent resection of at least one SB-NET in our European Neuroendocrine Tumor Society Center of Excellence were prospectively included, while patients with duodenal SB-NETs were excluded. The resection and pathological analysis of LNs were standardized using three groups (group 1, along the small intestine; group 2, along the mesenteric vessel; and group 3, retropancreatic and mesenteric vessel origin).Twenty-eight patients with SB-NET resection were prospectively enrolled in the study, with seven patients being excluded from the analysis because it was impossible to divide the operative piece into nodal groups due to retractile mesenteritis. Among the remaining 21 patients, 20 (95 %) had LNs involved; 8 (38 %) in group 1, 13 (62 %) in group 2, and 12 (57 %) in group 3. Skip metastases were found in 14 patients (67 %): 4 (19 %) with an invasion pattern of group 3+ without group 2+, and 12 (57 %) with an invasion pattern of group 2+ or group 3+ without group 1+.As a result of skip metastases, systematic, extensive LN resection in retropancreatic portion may be required to prevent unresectable locoregional recurrence.

Published
2016

17. PRODIGE 29-UCGI 26(NEOPAN): A randomised trial of chemotherapy with folfirinox or gemcitabine in locally advanced pancreatic carcinoma (PC)

Author

F. El Hajbi, Laetitia Dahan, P. Follana, J.P. Pignon, T. Brotelle, C. Jouffroy, P. Vanelslander, N. Baba Hamed, Olivier Capitain, Michel Ducreux, Y. Rinaldi, F. Di Fiore, M. Texier, A. Parzy, Julien Forestier, O. Bouche, R. Desgrippes, and Rosine Guimbaud

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Chemotherapy, FOLFIRINOX, business.industry, medicine.medical_treatment, Locally advanced, Hematology, Gemcitabine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Pancreatic carcinoma, business, medicine.drug
Published
2018
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18. Gemcitabine and oxaliplatin or alkylating agents for neuroendocrine tumors: Comparison of efficacy and search for predictive factors guiding treatment choice

Author

Anne-Sophie, Dussol, Marie-Odile, Joly, Cecile, Vercherat, Julien, Forestier, Valérie, Hervieu, Jean-Yves, Scoazec, Catherine, Lombard-Bohas, and Thomas, Walter

Subjects
Adult, Aged, 80 and over, Male, Alkylating Agents, Antimetabolites, Antineoplastic, Organoplatinum Compounds, Middle Aged, Deoxycytidine, Gemcitabine, Disease-Free Survival, Oxaliplatin, Neuroendocrine Tumors, Treatment Outcome, Humans, Female, Antineoplastic Agents, Alkylating, Aged, Retrospective Studies
Abstract

The alkylating agents (ALKYs) streptozotocin, dacarbazine, and temozolomide currently are the main drugs used in systemic chemotherapy for neuroendocrine tumors (NETs). The promising activity shown by gemcitabine and oxaliplatin (GEMOX) in previous studies prompted this study 1) to confirm the use of GEMOX in a larger population of NET patients, 2) to compare its efficacy with that of ALKYs, and 3) to explore whether the O(6) -methylguanine-DNA methyltransferase (MGMT) status could help in selecting the chemotherapy regimen.One hundred four patients with metastatic NETs (37 pancreatic NETs, 33 gastrointestinal NETs, 23 bronchial NETs, and 11 NETs of other/unknown origin) were treated with GEMOX between 2004 and 2014. Among these patients, 63 also received ALKYs. MGMT promoter gene methylation was assessed via pyrosequencing in 42 patients.Patients received a median of 6 courses of GEMOX. Twenty-four (23%) had an objective response (OR). The median progression-free survival (PFS) and overall survival were 7.8 and 31.6 months, respectively. In the 63 patients treated with both ALKYs and GEMOX, the ORs (22% and 22%) and the PFSs (7.5 and 7.3 months) were similar. The response was concordant in 53% of the patients. Promoter gene methylation of MGMT was associated with better outcomes with ALKYs (P = .03 for OR and P = .04 for PFS) but not GEMOX.GEMOX is effective against NETs; its activity is comparable to that of ALKYs, and it is not influenced by the MGMT status. Our data suggest that GEMOX might be preferred for patients with unmethylated MGMT tumors. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Published
2015

19. Endoscopic management of gastric wall bleeding and stent blood clot occlusion after endoscopic ultrasound-guided hepaticogastrostomy

Author

Jean Christophe Saurin, Caroline Fine, Mathieu Pioche, Jérôme Rivory, Leonardo Sosa-Valencia, Julien Forestier, and Thierry Ponchon

Subjects
Male, Endoscopic ultrasound, medicine.medical_specialty, medicine.medical_treatment, Hepatic Duct, Common, Endoscopic management, Endosonography, 03 medical and health sciences, 0302 clinical medicine, Melena, Gastroscopy, Occlusion, Humans, Medicine, Gastric wall, Ultrasonography, Interventional, Gastrostomy, medicine.diagnostic_test, business.industry, Anastomosis, Surgical, Hemostasis, Endoscopic, Stomach, Gastroenterology, Stent, Thrombosis, Middle Aged, Prosthesis Failure, Surgery, Hepaticogastrostomy, 030220 oncology & carcinogenesis, Stents, 030211 gastroenterology & hepatology, Radiology, business
Published
2016
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20. Macroscopic and histologic regression of duodenal polyposis with FOLFOX4 chemotherapy for an ileal pouch adenocarcinoma in a patient with familial adenomatous polyposis

Author

G. Aguero Garcete, C. Nozières, Catherine Lombard-Bohas, Julien Forestier, Jean-Christophe Saurin, Vincent Lepilliez, and Mathieu Pioche

Subjects
Adult, medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, Leucovorin, Colonic Pouches, Adenocarcinoma, Stage ii, Risk Assessment, Gastroenterology, Familial adenomatous polyposis, Duodenal Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, Duodenal polyposis, Duodenoscopy, Chemotherapy, business.industry, Biopsy, Needle, Proctocolectomy, Restorative, medicine.disease, Pancreaticoduodenectomy, Immunohistochemistry, Surgery, Treatment Outcome, Adenomatous Polyposis Coli, Chemotherapy, Adjuvant, Female, Fluorouracil, Pouch, business, Follow-Up Studies
Abstract

Severe (stage IV) duodenal polyposis is difficult to manage in patients with familial adenomatous polyposis (FAP), with no effective medical treatment, complex endoscopic treatment modalities, and a high morbidity and mortality from pancreaticoduodenectomy. We present the case of a 44-year-old woman with FAP, stage IV duodenal polyposis, and with an ileal pouch adenocarcinoma that required surgery and adjuvant chemotherapy. Her duodenal polyposis regressed to stage II after four sessions of FOLFOX4 adjuvant chemotherapy, which avoided the need for aggressive endoscopic therapy or pancreatoduodenectomy in this patient.

Published
2012
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22. Comparison of BEAMing assays and competitive approaches in the detection of main alteration of RAS in circulating DNA of non small-cell lung cancer (NSCLC) and metastatic colon cancer. Manuscript 2016

Author

Marie Brevet, Carole Ferraro Peyret, Anne-Sophie Wozny, Léa Payen, Thomas Walter, Claire Rodriguez-Lafrasse, Marielle Guillet, Karen Brengel-Pesce, Sébastien Couraud, Jessica Garcia, Marion Chauvenet, Valérie Cheynet, Eric Dusserre, and Julien Forestier

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Oncology, business.industry, Colorectal cancer, Cancer research, medicine, non-small cell lung cancer (NSCLC), Circulating DNA, medicine.disease, business, Metastatic colon cancer
Abstract

e23056 Background: A number of RAS mutations confer resistance to anti-EGFR therapies routinely used in the treatment of colon cancer. The objective of this study was to evaluate the pertinence of analyzing circulating-free plasma DNA (cfDNA) as an indicator of the mutational status of a tumor, in order to use liquid biopsies instead of invasive and painful tumor biopsies during tumor progression. Methods: A cohort of 24 lung and 25 colon cancer patients was constituted in the Hospices Civils of Lyon. Liquid biopsy plasma samples were collected at diagnosis (colon cancer) and during tumor progression (lung cancer) for the purpose of the current study. KRAS and NRAS somatic alterations were quantified using three different technologies: the Droplet Digital polymerase chain reaction (ddPCR) from BioRad, the BEAMing Digital PCR from Sysmex Inostics, and the NGS NextSeq 500 by Illumina with the Accel-Amplicon 56G Oncology Panel from SWIFT BIOSCIENCES. Results: We observed a high level of sensitivity and specificity with the BEAMing technology, which provided us with excellent matches, around 96% and 73%, between solid and liquid biopsies taken at diagnosis (colon cancer) or during tumor progression (lung cancer), respectively. Indeed, when examining cfDNA from patients displaying one of the KRAS or NRAS mutations, 11 of the 13 mutations were confirmed using this technology, whereas only 5-6 matched the initial NGS status, using the two other technologies. The detection threshold was estimated at 1% for samples containing at least 0.8 ngctDNA/µL for the multiplex screening ddPCR from BioRad and for the 56G Oncology Panel from SWIFT BIOSCIENCES. The threshold was lower, at 0.03%, in samples containing only 0.25 ng ctDNA/µL for the BEAMing technology, which includes a PCR pre-amplification step. Conclusions: The advantage of the Illumina NGS technology is the larger coverage of longer gene regions, and thus the detection of more genetic mutations. Finally, the BEAMing technology enabled us to follow the appearance and disappearance of somatic alterations, with a very high level of sensitivity.

Published
2017
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23. Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors

Author

C. Micol, V. Chey, Catherine Lombard-Bohas, V. Lepiliez, Thomas Walter, X. Chopin-laly, and Julien Forestier

Subjects
Male, Abdominal pain, medicine.medical_specialty, medicine.medical_treatment, Carcinoid tumors, Carcinoid Tumor, Catheterization, Hepatic Artery, medicine, Humans, Embolization, Chemoembolization, Therapeutic, Transcatheter arterial chemoembolization, Hepatology, business.industry, Liver Neoplasms, Gastroenterology, Middle Aged, medicine.disease, Pancreatitis, Hepatocellular carcinoma, Acute Disease, Acute pancreatitis, Radiology, medicine.symptom, Complication, business
Abstract

Acute pancreatitis is a rare side effect of non-selective transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma with an incidence ranging from 2% (clinical pancreatitis) to 40% (biological pancreatitis). This complication, due to embolization of extrahepatic arterial collaterals, has never been reported for treatment of well-differentiated endocrine carcinoma. We report here a case of acute clinical pancreatitis developing within 24 hours after a first selective TACE into the proper hepatic artery, with two peaks of hyperlypasemia, and intend to discuss its mechanism. Since it may clinically mimic a postembolization syndrome, dosage of serum pancreatic enzymes should be performed systematically in case of abdominal pain following TACE.

Published
2011
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25. Well-differentiated pancreatic islet cell carcinoma: Is there reversibility in mTOR inhibitor resistance?

Author

Jean-Yves Scoazec, Julien Forestier, Jean-Alain Chayvialle, Catherine Lombard-Bohas, Christophe Couderc, Thomas Walter, Colette Roche, DOCOMO Euro-Labs, DOCOMO Communications Laboratories Europe GmbH, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and Hospices Civils de Lyon (HCL)

Subjects
MESH : Carcinoma, Islet Cell, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, Lanreotide, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, Pancreatic tumor, MESH: Protein Kinase Inhibitors, MESH : Neoplasm Staging, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, MESH: Middle Aged, medicine.diagnostic_test, Sunitinib, MESH: Neoplasm Staging, Hematology, General Medicine, MESH: Drug Resistance, Neoplasm, 3. Good health, Portal vein thrombosis, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Drug Resistance, Neoplasm, Oncology, 030220 oncology & carcinogenesis, MESH : TOR Serine-Threonine Kinases, MESH: Pancreatic Neoplasms, MESH : Cell Differentiation, medicine.drug, MESH: Cell Differentiation, medicine.medical_specialty, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Biopsy, medicine, Carcinoma, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, MESH: TOR Serine-Threonine Kinases, Chemotherapy, MESH: Humans, Everolimus, business.industry, MESH : Humans, medicine.disease, MESH : Protein Kinase Inhibitors, MESH: Male, Surgery, chemistry, MESH: Carcinoma, Islet Cell, business, MESH : Pancreatic Neoplasms
Abstract

In 2000, a 48-year-old man presented with epigastralgia. Computed tomography scan revealed a hypervascular pancreatic tumor with multiple liver and mediastinal lymph node metastases. The diagnosis of metastatic well-differentiated pancreatic islet cell carcinoma (pNET) was made by biopsy of the liver lesions. The mitotic index was 3/10 HPF (x40); Ki67 index was 5%. Serum levels of digestive hormones were within normal limits and chromogranin A levels was 220 μg/l. Octreotide scintigraphy showed high-grade activity in liver and mediastinal metastases. The patient was successively treated with chemotherapy (six cycles of streptozotocin-doxorubicin); surgery (cephalic duo-denopancreatectomy in March 2002, due to the local risk of compression and presence segmental portal hypertension); without any treatment and stable disease until February 2004; alpha-interferon for 15 months; chemotherapy (ten cycles of Folfi ri); and everolimus in December 2006 (RADIANT 1 trial). The treatment resulted in a decrease in tumor size (34% using RECIST criteria) at four months; the dis-ease was controlled for 24 months. Because of occur-rence of two new liver metastases, the patient was then included in a phase 3 trial and received sunitinib throughout 12 months; sunitinib was stopped because of occurrence of portal vein thrombosis under enox-aparin; the disease was stable. The patient was then treated with lanreotide in order to maintain disease stabilization; however, new progression ( after a break in treatment or maybe induced by 10% among RECIST criteria and elevation of Chromogranin A from 1982 to 2932 μg/l) occurred three months later. In June 2010, as the patient refused cytotoxic chemo-therapy and because of the particular initial good response to the everolimus, it was decided to add everolimus in association with lanreotide. Three months after starting the treatment, the weight of the patient had increased by 3 kg, fatigue had disappeared and imaging studies showed a response of 23% on RECIST criteria. His disease remains stable six months after this combination started. To our knowledge, this is the fi rst case showing a second effi cacy of mTOR inhibitor for treatment of solid advanced cancer. It enables us to discuss the reversibility of resistance mechanisms of evero-limus, and potential interest of a combined therapy with somatostatin analogs. It has recently been shown that, in patients with pNET, sunitinib or everolimus signifi cantly increase progression-free survival [1,2]. However, even if a control of the disease is frequently achieved, objective responses, such as the one observed in our case, are rare. How can we explain the second effi cacy of everolimus in combination with somatostatin analogs 18 months after the end of the fi rst treatment, as reported here? Some hypotheses may be discussed: a) syner-getic antitumor effect between everolimus and somatostatin analogs; b) emergence of a predomi-nant tumor cell clone, responding to everolimus

Published
2011
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26. Carcinome endocrine bien différencié pancréatique métastatique : discussion de la stratégie thérapeutique

Author

Catherine Lombard-Bohas, Thomas Walter, and Julien Forestier

Subjects
Gynecology, medicine.medical_specialty, Pancreatic disease, Endocrine Tumor, business.industry, medicine.medical_treatment, Cancer, medicine.disease, Targeted therapy, Metastasis, medicine.anatomical_structure, medicine, General Earth and Planetary Sciences, Pancreas Carcinoma, business, Pancreas, General Environmental Science
Abstract

Les carcinomes endocrines bien differencies (CEBD) du pancreas sont des tumeurs rares. Leur prise en charge est complexe, ce qui a justifie la creation d'un reseau national de prise en charge des tumeurs endocrines (RENATEN), valide par l'INCa en 2009. Nous rapportons un cas de CEBD pancreatique avec metastases hepatiques et mediastinales synchrones. La longue evolution de la maladie (9 ans a ce jour) permet de discuter la strategie therapeutique autour de la multiplicite des traitements actuellement disponibles dans cette pathologie: chimiotherapie, chirurgie de la tumeur primitive et/ou des metastases hepatiques, analogue de la somatostatine, interferon, therapies ciblees (everolimus, sunitinib) radiotherapie metabolique.

Published
2010
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27. Prospective Endoscopic, Genetic, Molecular and Oncogenetic Characterization of Serrated Polyposis Patients

Author

Françoise Berger, Thomas Walter, Marco Petronio, Stéphane Pinson, Jean-Christophe Saurin, Jean-Yves Scoazec, Valérie Hervieu, Julien Forestier, and Marie-Odile Joly

Subjects
medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Genetic molecular, medicine.disease, Serrated polyposis, Alternative treatment, Surgery, Stenosis, medicine, Severe pain, Complication, business, Abscess, Severe complication
Abstract

according to the Goligher's classification. Results: The operation duration was significantly longer (p

Published
2011
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28. Prognostic value of metabolic liver function tests: A study on 711 cirrhotic patients

Author

Olivier Guillaud, Marie Ecochard, Fanny Lebossé, Sabine Roman, Julien Forestier, François Mion, Olivier Boillot, and Jérôme Dumortier

Subjects
Adult, Indocyanine Green, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, Decision Support Techniques, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Model for End-Stage Liver Disease, Liver Function Tests, Predictive Value of Tests, Internal medicine, medicine, Humans, Aminopyrine, Coloring Agents, Aged, Retrospective Studies, Breath test, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Reproducibility of Results, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Liver Transplantation, Breath Tests, Liver, ROC Curve, Area Under Curve, 030220 oncology & carcinogenesis, Predictive value of tests, Female, 030211 gastroenterology & hepatology, Liver function tests, business, Biomarkers
Abstract

Background & Aims: The prognosis of cirrhotic patients is usually assessed by Child-Pugh and MELD scores. Metabolic liver function tests such as aminopyrine breath test (ABT) and indocyanine green clearance (IGC) have been shown to reveal hepatocellular dysfunction. The aim of this retrospective study was to compare the prognostic value of the MELD score, Child-Pugh score, ABT and IGC in a large cohort of cirrhotic patients. Methods: Between January 1996 and June 2008, 711 cirrhotic patients were included and the primary endpoint was survival without LT. The ROC curves with c-statistics, correlation coefficient and survival were calculated. Results: Metabolic function tests and scores were strongly correlated. At the time of evaluation, 111 patients had died and 520 had received a transplant. Prognostic ability (estimated by the AUROC curve) to predict survival without LT at 6 months was 0.662, 0.691, 0.738 and 0.715 for ABT, IGC, Child-Pugh score and MELD score, respectively. Similarly, at 1 year, AUROC was 0.738 for Child-Pugh score, 0.716 for MELD score, 0.693 for IGC clearance and 0.651 for ABT. Conclusions: Our results strongly confirm that IGC and ABT have a high prognostic value in cirrhotic patients, similar to Child-Pugh and MELD scores. They could be developed to routinely evaluate the prognosis of patients in addition to clinical and biochemical data. Key words: – – – – – – . Abbreviations: ABT: Aminopyrine Breath Test; AUROC: area under the receiver operating characteristics curve; CP score: Child-Pugh score; DRI: deceased donor risk index; IGC: Indocyanine Green Clearance; LT: Liver transplantation; MELD: Model for End stage Liver Disease.

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