Overview of current European practice for the management of patients with intracranial germ cell tumours

Abstract

Central nervous system germ cell tumours (CNS GCT) form a diverse group of tumour entities, including germinoma, yolk sac tumour, embryonal carcinoma, choriocarcinoma, teratoma, and mixed tumours. Incidence peaks in the second decade, predominantly in males. Incidence rates vary globally, higher in Asia, suggesting genetic factors are important. CNS GCTs split into pure germinomas and non-germinomatous GCTs (NGGCT), influencing prognosis/treatment. Serum and CSF markers (alpha-fetoprotein, human chorionic gonadotropin) aid diagnosis, potentially avoiding neurosurgical biopsy. Histological features are distinguished by immunohistochemical staining. Studies have identified specific microRNAs in serum/CSF at diagnosis as promising biomarkers. Mutated pathways have been identified, but targeted therapies have shown limited success to date. Diagnosis involves recognising symptoms like raised intracranial pressure, endocrinological, and ophthalmological disturbances. MRI imaging is crucial for diagnosis and guiding treatment decisions. Treatment strategies vary, as pure germinomas respond well to chemotherapy and radiotherapy, or craniospinal radiotherapy alone, with excellent outcomes; in contrast NGGCTs demand aggressive combined chemo-radiotherapy, yielding generally inferior outcomes. Teratomas are typically chemo-/radio-resistant, requiring surgical intervention. Relapses need re-staging and (re-)biopsy consideration. Relapsed germinomas, though rare, may be cured with standard-dose chemotherapy and re-irradiation, or high-dose chemotherapy with stem-cell-transplantation, with/without further radiation. The more commonly observed NGGCT relapses have poor prognosis, even with thiotepa-based high-dose chemotherapy and stem-cell-transplantation delivered with curative intent. In summary, CNS GCT management integrates clinical, radiological, and histological findings, along with serum and CSF markers, for tailored treatment. Ongoing research aims to incorporate microRNA markers and molecular pathology for improved diagnosis, prognostication, and therapeutic intervention.