Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy.

Abstract

To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014. Thirty-four patients received induction chemotherapy followed by radiation with or without surgery. Median follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in these 34 patients (5-year overall survival [OS]: 88% versus 50%, P=0.0092), so analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-α-fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P=0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P=0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF-AFP at baseline. All three patients with ventricular relapse received local radiation therapy. NGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second-look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.