Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiation: Findings from the Third International Central Nervous System (CNS) Germ Cell Tumor (GCT) Study

Objectives To evaluate patterns of relapse and outcome in patients newly diagnosed with CNS Mixed Malignant GCT (MMGCT) treated initially with chemotherapy alone. Methods A retrospective chart review was conducted using all 25 patients enrolled on the International CNS GCT Study III, with at least 7 years follow-up for all surviving patients. Results Thirteen patients at diagnosis had CNS MMGCT by pathology and tumor markers (n = 11), or tumor markers alone (n = 2). Twelve received chemotherapy alone, one additionally receiving focal irradiation prior to relapse. Six patients (46%) relapsed (mean of 30.5 months; range 6–59 months), two beyond and four within the primary site alone. Three patients relapsed early (6–23 months from diagnosis), two with alpha-fetoprotein elevations and one without tumor markers assessed; all three expired of progressive disease at 2–10 months following initial relapse. Three patients relapsed late (37–59 months) without AFP elevations, one with pathologically pure germinoma, two with mild beta-human chorionic gonadotropin elevations; these patients survive disease-free at 86+, 94+, and 126+ months following additional treatment. Conclusions Patients with CNS MMGCT relapsing following chemotherapy alone display two distinct patterns of recurrence and outcome; patients relapsing early possess MMGCT elements and have a dismal prognosis, while patients relapsing late do so with pure germinomatous elements and have an excellent outcome. Current cooperative group studies utilizing more localized fields of irradiation should monitor closely the patterns of relapse and outcome; late recurrences with germinomatous elements might be avoided by initial use of low-dose larger field irradiation in select patients. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.