Abstract Background Salvage strategies for relapsed central nervous system germ cell tumors remain heterogeneous, with poorly defined outcomes, particularly in non-germinomatous germ cell tumor (NGGCT). At relapse, treatment approaches vary widely, including different chemotherapy backbones, high-dose chemotherapy, surgery, and re-irradiation, yet overall outcomes remain suboptimal. Methods Retrospective multicenter cohort study including 23 patients with relapsed CNS-GCTs treated according to SIOP-based protocols across 11 Spanish centers. Relapse patterns, therapeutic strategies delivered, and survival outcomes were analyzed. Results 16 NGGCT and 7 germinomas. Median age: 144 months.19 males. In NGGCT, radiological response after induction chemotherapy was clinically meaningful: median EFS was 33.0 months in patients achieving complete remission and 9.0 months in those with partial remission (p = 0.019). Among NGGCT patients evaluable for radiation field–based relapse analysis (n = 13), 8 (61.5%) experienced relapse outside the initially irradiated field, predominantly as spinal or metastatic intracranial disease. 9 NGGCT patients received HDCT and 6 received conventional chemotherapy, without a clear survival advantage associated with treatment intensification. The estimated 5-year overall survival (OS) in NGGCT was 45%. In germinoma, 5-year OS was 100%, and relapses tended to occur later than in NGGCT. Salvage strategies were effective, with durable disease control achieved in some patients without the need for re-irradiation. Conclusions In relapsed NGGCT, residual disease following induction chemotherapy is associated with significantly earlier relapse and poorer outcomes, reinforcing the importance of achieving optimal disease control before radiotherapy. The predominance of spinal and metastatic intracranial relapses suggests that focal or whole ventricular radiotherapy at diagnosis may be insufficient to prevent disease dissemination in a subset of patients, acknowledging that this cohort includes only relapsed cases. In germinoma, long-term survival after relapse is excellent, with late recurrences and effective salvage strategies, including durable disease control in selected patients without the need for re-irradiation, supporting prolonged follow-up.
Solano-Paez et al. (Tue,) studied this question.
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