Cracking the code: Clinical predictors of brain metastases in colorectal cancer.

Abstract

241 Background: Despite occurring in only 1-3% of metastatic colorectal cancer (mCRC) patients, brain metastases predict a strikingly poor median overall survival (mOS) of 2.6-7.4 months. There is limited data regarding the clinicopathological characterization of brain metastases (BMs) in mCRC. Although potential predictive patterns for brain metastases have been sparingly described, no guidelines exist for screening asymptomatic patients, limiting opportunities for earlier detection and intervention. A comprehensive understanding of the risk factors associated with the development of brain metastases in mCRC is essential to optimize detection and improve patient outcomes. Methods: Patients with mCRC and radiographically confirmed BMs were retrospectively identified utilizing the Palantir Foundry platform and review of patient electronic medical records. Between 2015 and 2024, data from 66 patients at MD Anderson Cancer Center (MDACC) and 37 from the Veneto Institute of Oncology were collected for data analysis. Clinicopathological data including gender, ethnicity, smoking history, tumor sidedness, and mutational status were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method. Results: In the MDACC cohort, baseline characteristics of the 66 patients revealed a median age of 54.4 years at the time of metastatic disease diagnosis, with approximately 55% being male. The majority of patients were Caucasian (72.7%) and had no history of smoking (65.2%). Most had lung metastases (92.4%), a rectal primary (57.6%), retained mismatch repair protein expression (98.5%), and harbored mutations in KRAS at initial diagnosis (65.2%) and TP53 (66.7%). A minority of patients were BRAF mutated (7.6%) or HER2 amplified (7.6%). BMs were most often seen in patients with indolent disease, evidenced by a median of 30.3 months from metastatic disease diagnosis to detection of brain involvement. The median OS from the time of BMs detection was 10 months, while mOS from metastatic disease diagnosis was 49 months. Of the 37 patients from the Veneto Institute of Oncology, 54.1% were male with a mean age of 58 years, and the primary tumor location was either the descending colon (40.5%) or rectum (40.5%). Consistent with the MDACC cohort, 59.5% of patients harbored KRAS mutations and 83.8% had lung metastases. The mOS was 42.9 months from the time of metastatic disease diagnosis and 11.5 months from the detection of BMs. Conclusions: BMs in mCRC are associated with a poor prognosis and routine screening is not currently standard practice. In this preliminary analysis of two separate institutional patient cohorts, similar clinicopathological features appear to be associated with BM development and warrant further investigation. We plan to design a multivariate model to estimate lifetime risk of BMs at presentation, with the aim of identifying high-risk individuals and developing earlier detection strategies.