Consensus and Controversy in Diagnosis and Treatment of Central Nervous Systems Germ Cell Tumors

Abstract

  Central nervous system germ cell tumors include five histologic types and mixed types, which can be classified into germinomas, malignant germ cell tumors, and other germ cell tumors as a clinical risk category. Internationally, two classifications, germinoma and non-germinomatous germ cell tumor (NGGCT), are used ; however, their validity is questionable due to tumor type complexity. The standard of care for germinomas is platinum-based chemotherapy followed by whole brain ventricular/whole-brain radiation therapy (23.4Gy in 13 fractions). For malignant germ cell tumors, alkylating agents and platinum-based chemotherapy followed by whole-brain whole-spinal cord irradiation and local radiation therapy (50-59.4Gy in 25-33 fractions). The 10-year overall survival (OS) rate of germinoma is good at about 90%, but late recurrence and radiotherapy-related adverse events are problems. The 10-year OS rate of malignant germ cell tumor is poor at about 60%, and late radiotherapy-related adverse events are an additional issue. In 2022, the Brain Tumor Committee of Japan Children's Cancer Group initiated a clinical trial in patients with primary central nervous system germ cell tumors to investigate reduced invasiveness in chemoradiation therapy. Proving of the study hypothesis is expected to establish a treatment that mitigates late adverse events.