PETACC-3 subpopulation of patients stratified by the 5-FU profile score, RFS.

<p>Same data as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155123#pone.0155123.g001" target="_blank">Fig 1A</a>, but presenting the results per treatment arm. Panel A shows the data of the patients in the 5-FU/FA arm, Panel B the data for the patients in the FOLFIRI treatment arm. The used endpoint is RFS.</p

Association between RFS and the 5-FU profile score in the subpopulation of the PETACC-3 study.

<p>Association between RFS and the 5-FU profile score in the subpopulation of the PETACC-3 study.</p

Patients from the Kennedy cohort stratified by the 5-FU profile score.

<p>Patients with a 5-FU profile score smaller or equal to 50 were labeled as low score, the other ones as high score in relation to 5-FU treatment. The curves show that the 5-FU profile does not separate the CC patients into good and poor outcome (using RFS as endpoint in panel A, OS in panel B).</p

PETACC-3 subpopulation of patients stratified by the 5-FU profile score.

<p>Patients with a 5-FU profile score smaller or equal to 50 were labeled as poor prognosis, the other ones as good prognosis in relation to 5-FU treatment. 5-FU was included in all patients' treatment. The curves show that the 5-FU profile significantly separates the patients into good and poor outcome (using RFS as endpoint in panel A, OS in panel B).</p

Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)—validation in two independent cohorts

<div><p>Introduction</p><p>Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented.</p><p>Methods</p><p>The profiles are correlations between <i>in vitro</i> sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel. An applied clinical samples filter focused the profiles to clinically relevant genes. The profiles were tested on 1) snap-frozen tumors from 133 patients with completely resected stage 1B-2 NSCLC randomized to adjuvant cisplatin and vinorelbine (ACV, n = 71) or no adjuvant treatment (OBS, n = 62) and 2) formalin-fixed paraffin-embedded (FFPE) tumors from 95 patients with completely resected stage 1A-3B NSCLC receiving adjuvant cisplatin and vinorelbine.</p><p>Results</p><p>The combined cisplatin and vinorelbine profiles showed: 1) univariate Hazard Ratio (HR) for sensitive versus resistant of 0.265 (95% CI:0.079–0.889, p = 0.032) in the ACV cohort and a HR of 0.28 in a multivariate model (95% CI:0.08–1.04, p = 0.0573); 2) significant prediction at 3 year survival from surgery in univariate (HR = 0.138 (95% CI:0.035–0.537), p = 0.004) and multivariate analysis (HR = 0.14 (95% CI:0.030–0.6), p = 0.0081). No discrimination was found in the OBS cohort (HR = 1.328, p = 0.60). The cisplatin predictor alone had similar figures with 1) univariate HR of 0.37 (95% CI:0.12–1.15, p = 0.09) in the ACV cohort and 2) univariate HR of 0.14 (95% CI:0.03–0.59, p = 0.0076) to three years. Functional analysis on the cisplatin profile revealed a group of upregulated genes related to RNA splicing as a part of DNA damage repair and apoptosis.</p><p>Conclusions</p><p>Profiles derived from snap-frozen and FFPE NSCLC tissue were prognostic and predictive in the patients that received cisplatin and vinorelbine but not in the cohort that did not receive adjuvant treatment.</p></div

Kaplan-Meier curves of the cohorts receiving adjuvant cisplatin and vinorelbine, disease-specific survival.

<p>The curves show the cohort receiving adjuvant chemotherapy (ACV) in JBR.10 (1A) divided by a score of 50 and of the RH-cohort also receiving ACV (1B) divided by a score of 50. Underneath each curve is a description of events and patients at risk at different time points. Red: Combined cisplatin and vinorelbine score > 50, predicted high-likelihood responders to ACV; black: Combined cisplatin and vinorelbine score ≤ 50, predicted low-likelihood responders to ACV.</p

Expected disease-specific survival based on a multivariable model in the ACV cohort of JBR.10.

<p>Curves shown for expected disease-specific survival based on the multivariate time-dependent model from JBR.10 with values of the combined profiles (DRP) of 10, 25, 50, 75 and 90 for a model including gender male, age 62 years, histology adenocarcinoma and stage 1 (A) and stage 2 (B).</p

Kaplan-Meier curve of observational cohort (OBS) JBR.10, disease-specific survival.

<p>The curves show the observational cohort from JBR.10 divided by a score of 50. Underneath the curve is a description of events and patients at risk at different time points. Black: Combined cisplatin and vinorelbine score > 50, predicted high-likelihood responders to ACV; red: Combined cisplatin and vinorelbine score ≤ 50, predicted low-likelihood responders to ACV.</p

Pooled cohorts, multivariate time-dependent model, endpoint disease-specific survival.

<p>Pooled cohorts, multivariate time-dependent model, endpoint disease-specific survival.</p

Uni- and multivariate model per study, endpoint disease-specific survival and overall survival.

<p>Uni- and multivariate model per study, endpoint disease-specific survival and overall survival.</p