Faculty, Staff and Student Publications

Publication Date

5-1-2025

Journal

Translational Oncology

Abstract

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) had CPM with extraperitoneal metastases. Patients with synchronous CPM and CLM had worse overall survival (HR 1.67 [95 %CI 1.26-2.22]). Mutations in ctDNA were noted in 110/145 (75.9 %) of CPM patients, with mutations in KRAS or PIK3CA ctDNA being associated with worse survival. Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly BRAF and KRAS, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.

Keywords

BRAF mutation, Circulating tumoral DNA, Colorectal cancer, KRAS mutation, Liver metastasis, Peritoneal metastasis

DOI

10.1016/j.tranon.2025.102379

PMID

40184716

PMCID

PMC12002894

PubMedCentral® Posted Date

4-3-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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