Prognostic value of circulating tumor DNA (ctDNA) detection during adjuvant chemotherapy in patients with stage III colorectal cancer: The interim report of a prospective, observational study.

Abstract

29 Background: Adjuvant chemotherapy (ACT) is the standard treatment for stage III colorectal cancers (CRC). However, optimal biomarker were still needed for individualized adjuvant strategies. Here, we conducted a prospective study in patients with stage III CRCs with combined ACT, to explore the prognostic effect of circulating tumor DNA (ctDNA) before and after ACT. Methods: The study enrolled 130 patients with stage III colon and rectal cancer (≥10cm from anal) who received curative resection without neoadjuvant therapy at Fudan University Shanghai Cancer Center. All patients received 3 or 6 months of ACT. The Roche AVENIO Surveillance Kit was used to assess somatic mutations by next-generation sequencing (NGS) in tissue, pre- and post-chemo plasma samples. The plasmas were collected 3-5 weeks after surgery and after last cycle of ACT, respectively. Patients were classified as ctDNA (+) or (-) based on the detection of SNVs identified in tumor tissue at an AF of at least 5%. Results: In the interim analysis, 116 tissues, 123 pre-chemo and 98 post-chemo plasmas were prospectively collected and detected, and a total of 86 matched samples were analyzed with a median follow-up of 12.0 months. ctDNA was detectable in 14 of 86 patients (16.3%) before ACT, and in 10 (11.6%) patients after ACT. After 1-year follow-up, longitudinal ctDNA analysis identified 6 of 12 early relapses (50.0%), while 6 in 69 patients (8.7%) who were both ctDNA (-) in pre- and post-chemo samples had early relapse. Before ACT, ctDNA(+) patients were 7 times more likely to relapse early than ctDNA(-) patients (HR, 7.372; 95% CI, 1.543-35.22; P = 0.012). Similarly, after ACT, ctDNA(+) patients were 13 times (HR, 13.37; 95% CI, 2.026-88.23; P = 0.007) more likely to relapse. Monitoring after ACT indicated that 7 of the 14 ctDNA(+) patients (50.0%) were cleared, and the early relapse rate decreased from 43.9% (3/7) to 28.6% (2/7) if ctDNA turned negative. Conclusions: ctDNA analysis can potentially change the postoperative management and surveillance strategies for stage III CRC by enabling risk stratification, monitoring ACT efficacy, and detecting early relapse. Clinical trial information: ChiCTR1800018754.