Overall Survival Prediction and Usefulness of Second-Line Chemotherapy in Advanced Pancreatic Adenocarcinoma

J Natl Cancer Inst. 2017 Oct 1;109(10). doi: 10.1093/jnci/djx037.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Ascites / etiology
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cancer Pain / etiology
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / secondary
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Gemcitabine
  • Health Status
  • Humans
  • Irinotecan
  • Jaundice / etiology
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nomograms*
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Proportional Hazards Models
  • Prospective Studies
  • Retreatment
  • Risk Factors
  • Smoking
  • Survival Rate

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Fluorouracil
  • Camptothecin
  • Gemcitabine