Ankit Dhiman, MBBS, MS
Postdoctoral Scholar
Department of Surgery, University of Chicago, Chicago, IL
Chicago, Illinois, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Over 50% of patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer recur after curative-intent cytoreductive surgery (CRS). A lack of sensitive imaging and diagnostic biomarkers is a significant cause of delay in detection and, thus, poor outcomes. Studies have suggested a promising role for plasma circulating tumor DNA (ctDNA) assays in monitoring recurrence and treatment response in various cancers, including CRC; however, their precise role in PM has yet to be defined. We investigated the role of a Next-generation Sequencing based tumor-informed Personalized ctDNA assay (Signatera™) in informing recurrence in patients with PM.
Methods:
Patients with PM from CRC or HGA adenocarcinoma underwent curative CRS and serial post-resection assessments of ctDNA. Patients with rising ctDNA levels were compared to those with stable, undetectable ctDNA levels. Primary outcomes were recurrence rates and ctDNA assay sensitivity in predicting recurrence. Secondary outcomes were ctDNA lead-time, disease-free survival (DFS), and performance of ctDNA compared to CEA levels.
Results:
Twenty-five patients (n=11 CRC, n=14 HGA) underwent CC-0/1 CRS and serial post-resection ctDNA assessments (median 2(2-5)). Rising ctDNA levels were seen in 14 patients, of which 86% recurred, compared to 18% in the stable ctDNA group (n=11) over a median follow-up of 12 months (p=0.001). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 86% and 82%, respectively. Median DFS in the rising ctDNA cohort was 11 months (IQR 6-12) and not reached in the stable ctDNA cohort (p=0.09). The median ctDNA lead-time was 2.5 months (IQR 1.5-4). CEA was less sensitive (57%) than ctDNA.
Conclusions:
This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with PM from CRC and HGA undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.