The role of neoadjuvant chemotherapy in the management of metastatic central nervous system germinoma: A meta-analysis

Background: The role of neoadjuvant chemotherapy in treating patients with metastatic central nervous system (CNS) germinoma is controversial. Methods: We compared the relapse-free survival (RFS) of different treatment modalities by performing a meta-analysis using published data. We summarized all data using standard descriptive statistics. We used the Kaplan–Meier method to estimate RFS and their corresponding 95% confidence intervals (CIs). We used the log-rank test for the comparison of survival functions. Results: We identified 97 patients with a median age at presentation of 15 years (range: 7–38). Sites of metastasis were cerebrospinal fluid (CSF) disease only (n = 12), brain parenchyma (n = 18), spinal cord (n = 9), ventricular and CSF (n = 10), ventricular only (n = 31), and other (n = 17). The 3-year RFS among patients who received any form of radiotherapy was 89% (95% CI: 83–96) compared with 0% for patients who received a chemotherapy-only regimen (p =.001). Five-year RFS among patients who received craniospinal irradiation (CSI) was 92% (95% CI: 84–100) compared with 76.4% (95% CI: 63–90) in the non-CSI group (with or without neoadjuvant chemotherapy) (p =.014). Five-year RFS of patients who received CSI less than 24 Gy with neoadjuvant chemotherapy was 100% compared with 92% (95% CI: 83–100) CSI dose greater than or equal to 24 Gy alone (p =.3). Conclusions: Our analysis does not support avoiding spinal irradiation among patients with radiographic metastatic CNS germinoma. Future studies are needed to confirm whether neoadjuvant chemotherapy will allow a reduction of irradiation dose without compromising survival.