Multiomic analysis for minimal residual disease detection: Addressing challenges in stage II-III colon cancer from COSMOS-CRC-01.

• DOI: 10.1200/jco.2024.42.3_suppl.180
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Yoshiaki Nakamura; Yuichiro Tsukada; Nobuhisa Matsuhashi; Tatsuro Murano; Manabu Shiozawa; Takeshi Kato; Eiji Oki; Masahiro Goto; Yoshinori Kagawa; Akiyoshi Kanazawa; Takashi Ohta; Akira Ouchi; Hideaki Bando; Hiroshi Uchigata; Chiemi Notake; Mingyang Cai; Shile Zhang; Thereasa A. Rich; Kimberly Banks; Takayuki Yoshino
• Keywords: Clinical endpoint; Regimen; Minimal Residual Disease

180 Background: A considerable number of patients with stage II-III colon cancer experience disease recurrence following definitive treatment while others may receive unnecessary toxicity from adjuvant chemotherapy. Minimal residual (MRD) detection through ctDNA analysis can be evaluated without reliance on tissue which comes logistic advantages and the only option for limited tumor specimens. Methods: COSMOS-CRC-01 is an ongoing biomarker study that enrolled resectable 0-III colorectal between January 2020 April 2021. Plasma samples clinical data were collected 28 days post-operatively every 3-6 months up to 5 years alongside radiographic imaging. Samples tested Guardant Reveal Infinity Oncology Platform MRD detection. This analytically validated multiomic NGS assay interrogates >700 genes ~15Mb methylated regions. bioinformatics algorithm trained CRC classifies each sample as detectable or undetectable based a predefined statistical likelihood threshold returns quantitative fraction. The primary endpoint was time (TTR) status. Results: subgroup 801 post-surgical plasma (4mL each, median input 19ng, 96% passed QC) 136 R0 resected follow-up months. at Day post-surgery chemotherapy both associated significantly shorter TTR (p<0.0001; Table). Sensitivity serial measurement 80% (95% CI, 56.3-94.3%), lead 5.3 highest locoregional (2/2), brain (1/1), liver (7/7), multiple (3/3) metastasis compared isolated lung (2/4) peritoneal (1/3) metastasis. Tumor fraction increased expected in closer Three recurred had KRAS G12C variants detected prior recurrence, suggesting potential early intervention targeted agents. Among 553 post-treatment 114 non-recurred patients, specificity 97.3% CI 95.6-98.5%). Conclusions: We show plasma-only genomic- methylation-based have sensitive specific cancer. Serial provides superior performance versus one-time detects targetable recurrence. [Table: see text]