Stereotactic radiosurgery and multimodal integration approaches for germ cell tumor brain relapse

Patients with germ cell tumors (GCT) relapsing with brain metastases (BM) can achieve durable control after multimodal salvage therapy, typically including radiotherapy (RT) and chemotherapy (CT). However, minimal data are available to inform the optimal integration of RT and CT or the appropriateness of stereotactic radiosurgery (SRS) as an alternative to whole brain radiotherapy (WBRT). This study describes outcomes after RT for BM relapse of GCT, focusing on multimodal approaches and outcomes of SRS.

Patients with BM relapse of GCT treated with RT between 2005 and 2023 were included. Multimodal approaches included: RT without CT (Group B1), RT with conventional-dose CT (Group B2), RT with high-dose CT (Group B3), and RT for progressing BM initially treated with CT alone (Group B4). RT approaches included SRS and WBRT. Overall survival (OS) after RT was evaluated with the Kaplan-Meier method and Cox proportional hazards model. Time from RT to intracranial progression (IP) was evaluated using cumulative incidence estimation with Gray's test and the Fine-Gray subdistribution hazard model, with death as a competing risk.

Sixty male patients were included. Groups B1-B4 included 20, 17, 13, and 10 patients, respectively. WBRT and SRS subgroups included 33 and 27 patients, respectively. Four-year OS and IP were 39% and 44%, respectively, and were not significantly associated with Groups B1-B4, nor the WBRT and SRS subgroups. SRS to a solitary BM, compared with multiple BM, was associated with superior OS (HR 0.21, p = 0.01) and IP (HR 0.27, p = 0.02). Among patients with a solitary BM, SRS and WBRT yielded similar rates of IP (p = 0.9).

Patients with GCT and BM relapse can achieve long-term survival and intracranial control with various multimodal strategies incorporating RT and CT. SRS may be a suitable option for solitary GCT BM, given equivalent intracranial control to WBRT.