Outcomes of CyberKnife Stereotactic Radiosurgery for the Brain Metastases in Patients with Li Fraumeni Syndrome

Background Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations and an increased risk of radiation-induced malignancies, posing significant challenges in the management of brain metastases (BM). Data regarding the safety and efficacy of stereotactic radiosurgery (SRS) for BM in this population remain limited. Methods We performed a retrospective analysis of patients with LFS who underwent SRS for BM at our institution. Patient-level, lesion-level, and treatment-related data were collected. Outcomes assessed included local tumor control (LTC), overall survival (OS), distant progression-free survival (DPFS), radiographic response, and treatment-related adverse events. Results A total of 5 patients with 16 BM lesions were treated with SRS. The median age at treatment was 49 years (range, 37–65). Lesions were typically small (median diameter 6.1 mm) and predominantly supratentorial (87.5%). Most lesions (93.7%) were treated with single-fraction SRS with a median prescribed dose of 24 Gy. LTC was 100% at 3 months, 6 months, and at last follow-up. Median OS and DPFS were 11.03 months (95% CI, 9.53–12.54) and 7.5 months (95% CI, 7.3–7.7), with all deaths attributable to systemic disease rather than neurological progression. Importantly, no cases of radiation necrosis or radiation-induced secondary malignancies were observed during a median follow-up of 45 weeks. Conclusions SRS demonstrated excellent local control and a favorable safety profile for the treatment of BM in patients with LFS. Given the tendency for lesions to be small and multifocal, along with the need to minimize radiation exposure, SRS represents a rational, focal treatment approach in this high-risk population. However, longer follow-up and prospective studies are needed to better define long-term safety, particularly regarding the risk of radiation-induced malignancies.