title: Overall Survival Prediction and Usefulness of Second-Line Chemotherapy in Advanced Pancreatic Adenocarcinoma.
abstract: In advanced pancreatic ductal adenocarcinoma (aPDAC), there is no consensual strategy for second-line chemotherapy (L2). Better discrimination of overall survival (OS) may help clinical decision-making. We aimed to predict OS from the beginning of L2 and to assess the benefit from chemotherapy among the identified risk groups.
  
  
  
  Analyses were derived from all consecutive aPDAC patients treated at Besancon University Hospital, Besancon, France, between January 2003 and December 2013 (n = 462). The association of 50 parameters with OS was evaluated using univariate and multivariable Cox analyses. Based on the final model, a prognostic nomogram and score were developed and externally validated. Patients in the external validation cohort who received L2 (n = 163) were treated at three French institutions between January 2010 and April 2016. All statistical tests were two-sided.
  
  
  
  In the development cohort, 395 patients (85.5%) were eligible for L2, of which 261 (66.1%) were treated. Age, smoking status, liver metastases, performance status, pain, jaundice, ascites, duration of first-line, and type of L2 regimen were identified as independent prognostic factors for OS in L2. The score determined three groups with median OS of 11.3 months (95% confidence interval [CI] = 9.1 to 12.9 months), 3.6 months (95% CI = 2.6 to 4.7 months), and 1.4 months (95% CI = 1.2 to 1.7 months), for low-, intermediate-, and high-risk groups, respectively ( P < .001). By applying the score in the population eligible for L2 but untreated, the chemotherapy benefit was statistically significant across all groups, but with a magnitude of the effect decreased statistically significantly from low- to high-risk groups ( P = .001 for treatment and risk groups interaction term). The ability of the score to discriminate OS was confirmed in the external validation cohort.
  
  
  
  This prognostic nomogram and score in patients with aPDAC can accurately predict OS before administration of L2 and may help clinicians in their therapeutic decisions.
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Vienot
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Beinse
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Louis
authors.initials: L
authors.lastname: de Mestier
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Meurisse
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Fein
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Heyd
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Cleau
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: d'Engremont
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Dupont-Gossart
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Lakkis
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Neuzillet
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001201:Ascites / Q000209:etiology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000072716:Cancer Pain / Q000209:etiology; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006304:Health Status; D006801:Humans; D000077146:Irinotecan; D007565:Jaundice / Q000209:etiology; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D049451:Nomograms; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019233:Retreatment; D012307:Risk Factors; D012907:Smoking; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine