Brain Metastases from Biliary Tract Cancer: Case Series and Clinicogenomic Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Biliary tract cancers (BTCs) are uncommon and generally carry a poor prognosis; with novel targeted therapies for specific tumor-related molecular alterations, outcomes for BTC patients appear to be improving. Brain metastases (BM) from BTC (BM-BTC) are rare, with limited data suggesting BM incidence rates between 0.15% and 1.4% among all BTC patients. Here, we report the largest series of BM-BTC patients to date and characterize these patients by tumor-related molecular alterations. <h3>Materials/Methods</h3> Retrospective review of 822 BTC patients seen at our center (a major tertiary referral center) from 2005 to 2021 was performed; BM-BTC patients were identified, and demographic, clinical, and molecular data were extracted. <h3>Results</h3> Twenty of 822 BTC patients (2.4%) were identified to have BM. Median follow-up time after primary BTC diagnosis was 99.8 months, and 33.8 months after BM diagnosis. Median time from primary diagnosis to BM development (diagnosis of BM) was 15.6 months (range, 1.1-66.0 months). Median overall survival (OS) from primary diagnosis was 32.0 months (2.9-99.8), and median OS from BM diagnosis was 6.5 months (0.3-33.8). Patients who underwent BM-directed therapy had significantly higher median OS from BM diagnosis than patients receiving supportive care only (6.7 vs 0.7 months, p<0.001). The BM-BTC cohort was enriched for TP53 (37%) and <i>BRAF</i> (26%) mutations. BM-BTC patients with <i>BRAF</i> mutation had improved OS after BM diagnosis (19.6 vs 4.2 months, p=0.048). <h3>Conclusion</h3> This study provides the largest series of BM-BTC patients to date, providing molecular characterization of this subgroup of BTC patients. <i>BRAF</i> mutations appear to be enriched among BM-BTC patients, found in 26% of BM-BTC patients in this series compared with 5-7% in larger non-BM BTC cohorts. With advances in targeted therapy for BTC patients with actionable mutations, examining a changing landscape of patterns of failure, with emphasis on brain metastases, is warranted.