1. Association of prognostic value of primary tumor location in stage III colon cancer with RAS and BRAF mutational status
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Julien Taieb, Jean-François Emile, Thomas Aparicio, Claire Mulot, Pierre Laurent-Puig, Josep Tabernero, Hampig Raphael Kourie, John Bridgewater, Jean-Luc Van Laethem, Ralyath Balogoun, Ramon Salazar, Enrico Mini, Pierre Michel, Côme Lepage, Karine Le Malicot, Gunnar Folprecht, Josef Thaler, Géraldine Perkins, Eric Van Cutsem, Olivier Bouché, Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Fédération Francophone de la Cancérologie Digestive, FFCD, Université Sorbonne Paris Cité ( USPC ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Vall d'Hebron University Hospital [Barcelona], Carl Gustav Carus University Hospital, Hôpital Erasme (Bruxelles), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Klinikum Wels Grieskirchen, UCL Cancer Institute [University College London], University College of London [London] ( UCL ), University Hospitals Leuven [Leuven], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Université Sorbonne Paris Cité (USPC), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University College of London [London] (UCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
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0301 basic medicine ,Oncology ,Cancer Research ,Colorectal cancer ,medicine.medical_treatment ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,0302 clinical medicine ,FOLFOX ,Gastrointestinal Cancer ,Medicine ,OXALIPLATIN ,Stage (cooking) ,education.field_of_study ,Cetuximab ,Brief Report ,Gastroenterology ,Prognosis ,Primary tumor ,3. Good health ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Life Sciences & Biomedicine ,Adjuvant ,medicine.drug ,medicine.medical_specialty ,Pronòstic mèdic ,Population ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,LEUCOVORIN ,PANITUMUMAB ,Stage III colon, RAS, BRAF ,Folinic acid ,03 medical and health sciences ,Càncer colorectal ,Internal medicine ,Gastrointestinal cancer ,education ,neoplasms ,Pathological ,Colorectal Cancer ,Splenic flexure ,Science & Technology ,Genetics and Genomics Oncology ,business.industry ,Proportional hazards model ,Cancer ,medicine.disease ,FLUOROURACIL ,digestive system diseases ,METASTATIC COLORECTAL-CANCER ,030104 developmental biology ,business - Abstract
IMPORTANCE: We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. OBJECTIVE: To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure. MAIN OUTCOMES AND MEASURES: The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status. RESULTS: Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results were found independently of the treatment received, and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. CONCLUSIONS AND RELEVANCE: Although right-sided tumor location is associated with poor survival in patients with metastatic CC as previously reported, the association with disease recurrence appears to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type. ispartof: JAMA ONCOLOGY vol:4 issue:7 ispartof: location:United States status: published
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- 2017
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