Abstract Background Relapsed CNS non-germinomatous germ cell tumors (NGGCT) are aggressive and often disseminated at relapse, raising the question of optimizing primary treatment and salvage therapy. Materials and Methods We retrospectively analyzed 13 children with relapsed intracranial NGGCT, recording sex, serum tumor markers at diagnosis and at progression, baseline metastatic status, primary treatment (including radiotherapy (RT) volumes), time to progression, and salvage therapy. Results The male-to-female ratio was 1.6:1; median age at initial diagnosis was 9.11 years (2.2–16.1). All patients were marker-positive at diagnosis (AFP n = 3; β-HCG n = 3; both n = 7); 5 had AFP 1000 ng/mL (high-risk). No metastases were detected at initial diagnosis. All patients received SIOP CNS GCT II–based therapy (chemotherapy n = 13; high-dose chemotherapy n = 3) and RT (focal n = 8; whole-ventricular irradiation (WVI) n = 4; craniospinal irradiation (CSI) n = 1). Complete response was in 5 and partial in 8 cases. Median time from completion of primary therapy to progression was 11.3 months (0–163). Metastatic progression occurred in 12/13 cases, most commonly involving the spinal neuraxis (n = 5) and ventricular system (n = 4). Tumor markers were elevated at progression in 9 patients (AFP n = 5; β-HCG n = 3; both n = 1). After focal RT, metastatic progression involved the spine in 3 cases and ventricles in 4; after WVI, no ventricular relapses occurred and sites of dissemination were spinal neuraxis (n = 2), pineal region (n = 1), and left frontal lobe (n = 1). Salvage therapy included chemotherapy in all patients, with high-dose chemotherapy in 4; RT was delivered in 8, including CSI in 4. At analysis, 8 patients were alive and 5 died from progressive disease. Median follow-up was 12.6 months (1.7–111.6). Conclusions In initially non-metastatic NGGCT, progression was predominantly metastatic and occurred soon after completion of primary therapy. These data suggest focal RT may be insufficient, particularly in high-risk patients, supporting consideration of expanded RT volumes in primary treatment and standardized salvage strategies.
Degtyarev et al. (Tue,) studied this question.