Delayed toxicity of whole brain radiotherapy (WBRT) in germ cell tumor (GCT) patients with central nervous system (CNS) metastases

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15511 Background: CNS metastases are uncommon in GCT. Incidence is 2–3% and is usually associated with extensive pulmonary metastases and/or high serum human chorionic gonadotropin levels. CNS metastases have been managed with WBRT and concomitant cisplatin-based combination chemotherapy. Our prior publication did not observe serious CNS toxicity (Int J Rad Oncol Biol Phys 22:17–22, 1991). Methods: We observed 5 patients with delayed CNS toxicity. Initial diagnosis was 1981 through 2003. Median age 23 years (range 21–34). All 5 patients had advanced disease by the International Germ Cell Consensus Collaborative Group. Three of five patients had CNS metastases at the time of diagnosis, and two patients relapsed with CNS metastases. These 5 patients received WBRT 4,000–5,000 cGy in 18- 28 fractions concurrently with cisplatin-based chemotherapy. Results: All five patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy (PMLE), including seizures, hemiparesis, expressive and receptive aphasia, cranial neuropathies including facial droop, tremors, headaches, blindness, dementia, decreased level of consciousness, ataxia, and parasthesias. Median time from WBRT to CNS symptoms was 72 months (range 9–228 months). Brain imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. One patient was diagnosed with glioblastoma multiforme in the area of radiation-induced gliosis. 3 of 5 patients had progressive symptoms, and the other 2 had stable symptoms. Treatment with surgery and steroids had modest benefit. The PMLE resulted in significant debility in all five patients, resulting in death (2 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusions: WBRT is not innocuous in young patients with GCT and can cause late CNS toxicity. We are now cautious about the use of WBRT and reserve it for multiple CNS metastases that are symptomatic or resistant to chemotherapy. No significant financial relationships to disclose.