457P Circulating tumor DNA (ctDNA) from patients (pts) with advanced colorectal cancer (CRC) is enriched for EGFR extracellular domain (ECD) mutations

Abstract

Background: Tumor lymphocyte infiltrates (e.g. Immunoscore) and systemic inflammatory indices (SII) are highly prognostic in colon cancer but combined assessment is less well studied. The aim of this study was to investigate the prognostic and predictive value of CD8 + tumor-infiltrating lymphocytes (TIL) in combination with SII in patients with resected stage II-III colon cancer (CC).Methods: Patients with stage II-III CC (n¼304) diagnosed between 2008-2016 in our hospital were included. Pan-immune inflammation value (PIV) was calculated as; (neutrophil count  platelet count  monocyte count)/lymphocyte count. The mean density of CD8 + TILs in the periphery and center of the tumor was assessed and dichotomized at the 75 th percentile. Combined inflammation score (CIS) was classified as "high" in patients with high PIV (>median) and low mean CD8 + TIL density, and "low" in the remaining patients.Results: Five year DFS was 71% (78% in stage II, 64% in stage III). CD8 + TIL density was lower in node positive tumors and higher in mismatch repair deficient tumors, no association was observed with age, tumor sidedness or systemic inflammation indices. High PIV (>491), low CD8 + (<46 /mm 2 ) and high CIS were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 (vs <65) years (HR: 3.12 95% CI 1.78-5.48 p <0.001), stage 3 (vs. 2) disease (HR: 1.82 95% CI 1.06 3.12 p ¼ 0.029) and high (vs low) CIS (HR: 3.82 95% CI 2.21-6.61 p <0.001) were associated with shorter DFS. Among patients with stage II disease, 78 patients (52%) received adjuvant chemotherapy. Patients with high CIS derived significant benefit from adjuvant chemotherapy (5 yr DFS 100% vs 60%, p¼0.008) while those with low CIS derived no benefit (5 yr DFS 88 vs 89% p¼0,94). (Table ) Conclusions: Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.Legal entity responsible for the study: The authors.

Early circulating tumor DNA dynamics as a pan‐tumor biomarker for long‐term clinical outcome in patients treated with durvalumab and tremelimumab

“…Baseline, week 4 and week 8 MTM/mL values, number of variants tracked per sample, as well as TMB and PD‐L1 are listed in Table S1. Higher ctDNA shed into blood was anticipated in the colorectal and mixed solid tumor disease groups based on previous analyses [16,26]; accordingly, in these groups, 100% and 87.5% of successfully assayed samples, respectively, had detectable baseline ctDNA, compared with the lower shed groups of glioma (50%) and sarcoma (28.6%). The median quantitative measure of baseline ctDNA in detectable samples similarly varied as follows: colorectal (325 MTM/mL), mixed solid tumor (135 MTM/mL), glioma (0.20 MTM/mL), and sarcoma (0 MTM/mL; Fig.…”