PEDT-10 PHASE II TRIAL OF PATHOLOGY-BASED THREE-GROUP TREATMENT STRATIFICATION FOR PATIENTS WITH CNS GERM CELL TUMORS: A LONG-TERM FOLLOW-UP STUDY

BACKGROUND: Phase II clinical trial funded by Ministry of Health, Labour and Welfare from 1995 to 2003 evaluated efficacy of pathology-based three-group treatment stratification for CNS germ cell tumors (GCTs). We here present long-term follow-up results. METHODS: Total 228 cases were registered. Germinoma was treated with carboplatin+etoposide (CARE) and extended-local irradiation, local irradiation was added for intermediate-prognosis-group, and poor-prognosis-group was treated with ifosfamide+cisplatin+etoposide (ICE) and whole-brain or craniospinal irradiation. RESULTS: Mean/median ages at diagnosis were 16.8/16 years and female-to-male ratio was 40-188. Registry included 123 germinomas, 76 intermediate-prognosis-group cases (including 38 germinoma with STGC), 28 poor-prognosis-group cases and 1 mature teratoma. Median 222-months follow-up was conducted, and 56 recurrences and 39 deaths were recorded. 10 and 20-year recurrence-free survival (RFS) for germinoma, intermediate and poor-prognosis-groups were 84/79%, 83/76% and 59/59%, respectively, and overall survival (OS) for each were 97/91%, 92/85% and 57/53%, respectively. Prognosis for germinoma with or without STGC was the same. Basal ganglia germinoma showed significantly shorter RFS but OS was not different from other locations. Median age at death was 24 years, and ages were significantly different depending on causes, such as disease-related (14 years on average) and complications (29 years). OS after recurrence at 5/10/20 years were 64/62/48%.Hormonal supplementation was seen in 82% for neurohypophyseal cases and antidiuretic hormone supplementation was most frequent (82%). Among available cases, 20-out-of-155 cases showed neoplastic/vascular complications, among which cavernous malformation was the most (n=9). Median period until complication presentation was 235 months, and the rate at 20 years was 11%. CONCLUSIONS: Germinoma and intermediate-prognosis-group cases showed long-term survival for approximately 90%, while more intensive treatment would be necessitated for poor-prognosis-group. Long-term survivors often required hormonal supplementation, and increasing frequency of treatment-related complications was observed. There is no end of outpatient follow-up for CNS GCT patients.