Delayed effects of whole brain radiotherapy in germ cell tumor patients with central nervous system metastases.
OBJECTIVE
Central nervous system (CNS) metastases are uncommon in patients with germ cell tumors, with an incidence of 2-3%. CNS metastases have been managed with whole brain radiotherapy (WBRT) and concomitant cisplatin-based combination chemotherapy. Our previous study did not observe serious CNS toxicity (Int J Radiat Oncol Biol Phys 1991;22:17-22). We now report on 5 patients who developed delayed significant CNS toxicity.


METHODS
We observed 5 patients with delayed CNS toxicity. The initial diagnosis was between 1981 and 2003. All patients had poor-risk disease according to the International Germ Cell Consensus Collaborative Group criteria. Of the 5 patients, 3 had CNS metastases at diagnosis and 2 developed relapses with CNS metastases. These 5 patients underwent WBRT to 4,000-5,000 cGy in 18-28 fractions concurrently with cisplatin-based chemotherapy.


RESULTS
All 5 patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy. The symptoms included seizures, hemiparesis, cranial neuropathy, headaches, blindness, dementia, and ataxia. The median time from WBRT to CNS symptoms was 72 months (range, 9-228). Head imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. Of the 5 patients, 3 had progressive and 2 stable symptoms. Treatment with surgery and/or steroids had modest benefit. The progressive multifocal leukoencephalopathy resulted in significant debility in all 5 patients, resulting in death (3 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations.


CONCLUSIONS
Whole brain radiotherapy is not innocuous in young patients with germ cell tumors and can cause late CNS toxicity.
Doyle
Danielle M
DM
Department of Medicine, Division of Hematology and Oncology, Indiana University, Indianapolis, IN 46202, USA. dpeoni@iupui.edu
Einhorn
Lawrence H
LH
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D002822:Choriocarcinoma / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D006063:Chorionic Gonadotropin / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016371:Cranial Irradiation / Q000009:adverse effects*; D017809:Fatal Outcome; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D011832:Radiation Injuries / Q000150:complications*; D011879:Radiotherapy Dosage; D016879:Salvage Therapy / Q000379:methods; D033581:Stem Cell Transplantation; D013736:Testicular Neoplasms / Q000188:drug therapy; D013997:Time Factors
D006063:Chorionic Gonadotropin; D009363:Neoplasm Proteins; D002945:Cisplatin