LAUSR

OBJECTIVE To investigate the role of a personalized, tumor-informed ctDNA assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative CRS-HIPEC. SUMMARY BACKGROUND DATA Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in detection of recurrence and initiation of further therapies. Plasma circulating tumor DNA (ctDNA) has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial post-resection ctDNA assessments were included. Patients with rising post-operative ctDNA levels were compared to those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival (OS), ctDNA sensitivity, lead-time, and performance of ctDNA compared to CEA. RESULTS 130 serial post-resection ctDNA assessments (median 4, Interquartile range [IQR], 3-5) were performed in 33 patients (n=13 CRC, n=20 HGA) who underwent CC-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n=14, P<0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6-12) and not reached in the stable (P=0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI, 1.06-12.66, P=0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead-time was 3 months (IQR 1-4). CEA was less sensitive (50%) than ctDNA. CONCLUSIONS This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.