Tumoral and circulating genomic landscape inform survival differences in colorectal carcinomatosis

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.

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Publication Details

Journal
Translational Oncology
Published
2025-04-06
DOI
https://doi.org/10.1016/j.tranon.2025.102379
Primary Topic
Colorectal Cancer Treatments and Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Tumoral and circulating genomic landscape inform survival differences in colorectal carcinomatosis

Scott Kopetz, Christopher P. Scally, Keith F. Fournier, Michael G. White et al.
2 links
Translational Oncology
Colorectal Cancer Treatments and Studies
article

Tumoral and circulating genomic landscape inform survival differences in colorectal carcinomatosis

Scott Kopetz, Christopher P. Scally, Keith F. Fournier, Michael G. White, Mahmoud Yousef, Mohammad A. Zeineddine, Fadl A. Zeineddine, George J. Chang, Abhineet Uppal, Abdelrahman Yousef, Jason A. Willis, J. Bryan Iorgulescu, Timothy Eric Newhook, Reed I. Ayabe, Norman Galbraith, John Paul Shen, Y. Nancy You
article en

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.

Translational OncologyVol. 55
The University of Texas MD Anderson Cancer Center (US), Emory University (US), University of California, Irvine Medical Center (US)
Conquer Cancer Foundation, Cancer Prevention and Research Institute of Texas, University of Texas Health Science Center at Houston, National Institutes of Health, University of Texas MD Anderson Cancer Center
Openalex Percentile: Top 90%
Colorectal Cancer Treatments and Studies
DOIOpen Access PDFOpenAlex
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