Abstract A012: Mutation analysis of SCLC patients with distant metastases

Abstract Small cell lung cancer (SCLC) is a highly proliferative and aggressive type of lung cancer, accounting for 10–15% of all lung cancer cases. SCLC is characterized by early metastasis, with more than half of the cases presenting with metastases at the time of diagnosis. While comprehensive genomic studies have been performed for SCLC, metastasis-associated mutations have not been fully characterized. In this study, 57 SCLC samples from the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC), profiled by either FoundationOne CDx or Guardant360 CDx between 2013 and 2022, were analyzed. The most common metastatic sites were identified as the brain (54.3%), liver (45.6%), and bone (33.3%). Associations between clinical features and distant metastases were examined, with no significant differences observed in age, sex, race, or smoking status among the metastatic groups. To explore the relationship between gene mutation rates and distant metastatic sites, we collected somatically altered genes from these patients. Stratified by metastatic site, Cox proportional hazards regression analysis was performed to identify mutations associated with the progression of metastases. BRCA2 and APC alterations were significantly associated with brain metastases, while PDGFRA mutations were linked to liver metastases. No mutations were found to be associated with bone metastases. Our findings suggest the potential efficacy of PARP inhibitors for treating brain metastases and PDGFRA inhibitors for addressing liver metastases in SCLC. Validation in SCLC animal model is under investigation. This study reveals specific mutations associated with metastatic progression to the brain and liver. These findings underscore the importance of precision medicine approaches in tailoring treatments based on the genetic profile of tumors, offering the potential to improve outcomes for patients with this aggressive cancer. Citation Format: Yin Liu, Yuezhu Wang, Ralph D’Agostino, Jimmy Ruiz, Lance D Miller, Wencheng Li, Michael D Chan, Liang Liu, Fei Xing. Mutation analysis of SCLC patients with distant metastases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A012.