Circulating Tumor DNA as a Novel Prognostic Biomarker of Therapeutic Efficacy in Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

Abstract

Hepatic arterial infusion (HAI) chemotherapy is an expanding treatment for patients with unresectable colorectal liver metastases (uCRLM). This study examined circulating tumor DNA (ctDNA) as a novel biomarker to prognosticate oncologic outcomes after HAI. The study examined HAI outcomes for patients with uCRLM at Duke University from February 2022-December 2024. Signatera was used to determine circulating tumor DNA (ctDNA) quantity as mean tumor molecules per mL (MTM/mL). Survival outcomes were calculated from the date of HAI initiation and compared using Kaplan-Meier and Cox proportional hazards methods. In this study, 37 patients had ctDNA collected with 20 months of median follow-up time.. The patients with pre-HAI ctDNA ≤ 100 MTM/mL had a significantly better overall survival (OS) (hazard ratio [HR] of 5.5 (95% confidence interval [CI] 1.3-22.7; p = 0.05). After 3 months of HAI, the patients whose ctDNA decreased by less than 75% had significantly worse progression-free survival (PFS) (< 75% vs 75-99% vs 100% decrease; median PFS, 3 vs 10 vs 11 months; p < 0.01, log rank test) and OS (< 75% vs 75-99% vs 100% change; median, 10 months vs not reached [NR] vs NR; p = 0.01, log rank test). Although the patients with initial carcinoembryonic antigen (CEA) ≤ 10 ng/mL had significantly better OS than those with a CEA > 10 ng/mL (HR 2.5; 95% CI 1-6; p = 0.04), the magnitude of CEA change after 3 months of HAI was not associated with OS or PFS. Preoperative ctDNA and ctDNA dynamics were associated with oncologic outcomes for patients who had uCRLM treated with HAI. These hypothesis-generating findings require validation before quantitative ctDNA is incorporated into patient selection algorithms and ctDNA dynamics are used to guide HAI therapy for uCLRM.