Tumor mutations associated with outcomes in colorectal peritoneal metastases.

Authors

null

Abhineet Uppal

MD Anderson Cancer Center, Houston, TX;

Abhineet Uppal , Michael White , George J. Chang , Fadl A. Zeineddine , Mohammad A. Zeineddine , Abdelrahman M.G. Yousef , Christopher Scally , Keith F. Fournier , Timothy E. Newhook , Y. Nancy You , Jason Willis , Scott Kopetz , John Paul Y.C. Shen

Organizations

MD Anderson Cancer Center, Houston, TX; , The University of Texas MD Anderson Cancer Center, Houston, TX; , University of Texas MD Anderson Cancer Center, Houston, TX; , Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; , NSABP/NRG Oncology, and The University of Texas MD Anderson Cancer Center, Houston, TX; , Moores Cancer Center, La Jolla, CA;

Research Funding

No funding received
None.

Background: The association between tumor mutations beyond KRAS and BRAF for patients with peritoneal metastases (PM) from colorectal cancer (CRC) are poorly understood. Here we describe these associations with survival after diagnosis of PM. Methods: CRC patients with PM with or without synchronous liver or lung metastases treated at a single institution from 2016 to 2020 were retrospectively studied. Standard of care next-generation sequencing was performed on tissue specimens with a targeted panel of genes frequently mutated in cancer. Clinical data, including survival and last contact, were obtained from medical records. Multivariate Cox regression was used to identify associations between overall survival after diagnosis of PM (OS) with clinical, histopathologic and somatic mutation data. Results: Of 526 PM patients, 179 (34.2%) also had synchronous liver metastases, and these patients had worse OS compared to PM alone (HR 1.67, [1.26-2.22], p=0.0003). Lung metastases were identified in 57 (10.8%) and were not associated with worse OS (HR 1.34, [0.90-1.97], p=0.15). Poorly differentiated grade (HR 2.08, [1.42-3.04], p=0.0002), mucinous histology (HR 1.44, [1.07-1.94], p=0.016), male gender (HR 1.37, [1.05-1.78), p=0.019), and age (HR 1.02, [1.01-1.04], p=0.004) were independently associated with OS. Tumor sequencing data was available for 442 (87%) patients. TP53 was the most common mutation (61.5% of patients) and was associated with decreased OS (HR=1.51 [1.12-2.02], p=0.005). BRAF mutation (85% of which were V600E) was identified in 9.7% of patients and was also associated with decreased OS (HR=1.88 [1.23-2.86], p=0.003). In contrast, PTEN mutation (4.3%) was associated with improved OS (0.41 (0.17-0.99), p=0.049), while both KRAS (51.4%) and SMAD4 mutations (16%) were not (KRAS: HR 0.94, [0.72-1.24], p=0.68; SMAD4: HR 0.78, [0.53-1.16], p=0.21). Conclusions: Mutational data for PM patients has a distinct profile and unique associations with OS when compared to other sites of metastatic disease. TP53 and BRAF mutations were associated with worse survival, while PTEN mutation was associated with improved OS. KRAS mutation was more prevalent than expected in an unselected cohort, and not associated with OS. A better understanding of PM-specific associations with survival may influence treatment strategies for this difficult disease site.

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Abstract Details

Meeting

2023 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Colorectal Cancer,Anal Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 41, 2023 (suppl 4; abstr 196)

DOI

10.1200/JCO.2023.41.4_suppl.196

Abstract #

196

Poster Bd #

K18

Abstract Disclosures

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