Is liquid biopsy useful in patients with GI malignancies and exclusive peritoneal disease?

Abstract

809 Background: Peritoneal carcinomatosis (PC) is a common manifestation in gastro-intestinal (GI) cancers.10-20 % of patients (pts) will present isolated, unresectable peritoneal disease with poor prognosis. In the past years, circulating tumor DNA (ctDNA) has emerged as a novel and less invasive biomarker for molecular diagnosis and disease monitoring. We aimed to evaluate the ability of PC to shed ctDNA into circulation in a cohort of pts with GI cancers and isolated PC treated in our institution. Methods: We reviewed retrospectively the results of liquid biopsies obtained at progression or at diagnosis. Genomic analysis was done using Foundation One liquid CDx panel. Data on demographics, tumor type, clinical outcomes and molecular alterations (MA) have been collected. Results: Out of 400 GI pts tested, 85 with exclusively PC were included in the analysis. The main characteristics were as follows: 45(53%) female, median age of 57 years (IQR: 24-79), majority have received systemic chemotherapy (all were progressive) (n=63, 74%) with median number of previous lines 1 (range: 0-3). Most common tumor types were as follows: gastric (n=24, 28%), colorectal (n=22, 26%) and primary peritoneal (n=20, 24%) cancers. The median index of peritoneal carcinomatosis was 23(IQR: 6-39). The tumor fraction was very low or undetectable in a proportion of 81% (n=69), median Tumor Mutational Burden was 1 mutation per megabase and was not correlated to tumor volume. Gene alterations were found in a proportion of 56% of pts (n=48) but most common alteration were TP 53 (n=22 pts, 26%) and KRAS mutation (n=14 pts, 16%). Targetable MA were identified only in 11 pts (13%) as follows: ATM, ARID1A, BRAFV600E, ERBB2, krasG12C. Three of them were included in a clinical trial. Germline mutations were found in 5 pts: ATM, CDH1, BRCA2, MSH6, BAP1. For colorectal pts known KRAS and BRAF V600E mutations were confirmed in plasma in a proportion of 32% (7 pts out of 22), for pancreatic cancer the KRAS in 17% (3 out of 18) and for gastric cancer, ERBB2 amplification in 5% (1 out of 22 pts). In pts with primary peritoneal disease: pseudomyxoma and mesothelioma, one patient harbored a known germline BAP 1 and kras G12C mutation without other targetable MA. The median survival in MA group was higher compared to non-MA. Conclusions: Isolated Pc and primary peritoneal cancers have distinct clinical and biological characteristics. The clinical utility of ctDNA seems to be limited in isolated PC or primary peritoneal cancers. However, it is not very clear if this to tumor location or to the ability of peritoneum to seed ctDNA.