Treatment Approach for Metastatic Intracranial Germinoma: A Multi-Institutional Experience

Background: Germinoma is the most common intracranial germ cell tumor (IGCT) in children and young adults. Treatment with 24 Gy craniospinal irradiation (CSI) with boost to 40 Gy alone results in excellent survival, irrespective of disease stage. For localized germinoma, recent studies have demonstrated the efficacy of pre-irradiation induction chemotherapy in decreasing the field and dose of radiation therapy (RT) needed for cure. For metastatic germinoma, however, the optimal RT approach when combined with chemotherapy is unclear. Herein, we present our experience treating patients with metastatic germinoma. Methods: We performed a retrospective, IRB-approved study of patients with metastatic intracranial germinoma diagnosed between 1998 and 2023 at BCH, DFCI, BWH, and MGH. Clinical features, treatment details, and outcomes were collected and analyzed using the Kaplan-Meier method and Fisher's exact test. Results: Twenty-seven patients with metastatic germinoma were identified. Median age at diagnosis was 15.5 years (range: 6.2-25.9). Six patients received CSI only. Twenty-one patients received induction chemotherapy followed by CSI, with a median CSI dose of 21 Gy (range: 18-36 Gy) and a median involved field (IF) boost to 36 Gy (range: 30-51.6 Gy). Median duration of follow-up was 11.3 years (range: 0.24-24.3). There were no recurrences or deaths within the cohort. Analysis of long-term outcome data revealed a high frequency of endocrinopathies and radiographic CNS vasculopathy. Conclusions: Our data show that pre-irradiation induction chemotherapy followed by CSI is associated with excellent overall survival in patients with metastatic germinoma. Importantly, our experience suggests that in combination with induction chemotherapy, 21 Gy CSI may be sufficient as a curative dose in this patient population.