Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study

Abstract

Background: The Immunoscore (IS), which prognostically classifies stage IeIII colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. Patients and methods: Densities of CD3þ and CD8þ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. Results: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int þ High [hazard ratio (HR) ¼ 1.54; 95% confidence interval (CI) 1.24e1.93, P ¼ 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23e70.94) for IS Low and 77.14% (95% CI 73.50e80.35) for IS Int þ High. In multivariable analysis, IS remained significantly independently associated with DFS (P ¼ 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P ¼ 0.057). IS Int þ High significantly predicted benefit of 6 months of treatment (HR ¼ 0.53; 95% CI 0.37e0.75; P ¼ 0.0004), including clinically low-and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. Conclusions: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatinbased chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int þ High. These results will be validated in an external independent cohort.

Immunity to live: an immunopathoscore using the consensus Immunoscore to best define the risk of recurrence and death in stage IV metastatic patients

“…The prognostic value of Immunoscore has been demonstrated in Stage I/II/III, Stage II, Stage III, [6][7][8] and its predictive value of response to chemotherapy demonstrated for randomized phase 3 trial of Stage III patients. 13 These results further reinforce the clinical utility of Immunoscore in Stage IV patients. 1 Tumor and immunological markers are shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches.…”

Adjuvant Chemotherapy for Stage III Colon Cancer

“…The relative contribution of the Immunoscore ® to predict survival was better than the known prognostic factors: N stage, T stage, differentiation, VELIPI, sex, and MSI status [77]. The results of Immunoscore ® in the IDEA-France trial (including 1062 patients), recently published, have confirmed the prognostic value of Immunoscore ® in stage III CC and a beneficial effect of 6 months of FOLFOX/CAPOX in high or intermediate Immunoscore ® patients, independently of high-risk/low-risk group (T4/N2 or T1-3/N1), in contrast to patients with a low Immunoscore, for whom 6 months of treatment did not seem to improve patient outcomes [78]. A recent work using artificial intelligence showed that a predictive nomogram based on immune infiltrates and clinical variables identified a group of patients with less than 10% relapse risk and a group with a 50% relapse risk in stage III patients [79].…”

The consensus Immunoscore in phase 3 clinical trials; potential impact on patient management decisions

“…Densities of CD3+ and CD8 + T cells in the tumor and invasive margin of each patient were determined by immunohistochemistry, quantified by digital pathology, and converted into the pre-defined consensus Immunoscore for the 1062 available patients of the study. 3 Immunoscore Low and High were observed in 43.6%, 56.4% of patients, respectively. Immunoscore-Low identified patients at higher risk of relapse or death compared to Immunoscore-High (HR = 1.54; 95% CI, 1.24-1.93, P = .0001).…”

“…1 The Immunoscore-IDEA France study was conducted in collaboration with PRODIGE, a digestive oncology intergroup gathering the GERCOR, the FFCD and UNICANCER organizations. 2,3 The two studies were performed, using the pre-defined consensus Immunoscore, and included 559 patient samples from the FOLFOX alone arm of the NCCTG-N0147 trial, and 1062 patient samples from both arms (3 vs 6 months) of the IDEA France trial.…”