Metastasis S tage, A djuvant T reatment, a nd R esidual T umor Are P rognostic F actors f or M edulloblastoma i n C hildren: Conclusions F rom t he C hildren's C ancer G roup 9 21 Randomized P hase I II S tudy

Purpose: From 1986 to 1992, ''eight-drugs-in-one- day'' (8-in-1) chemotherapy both before and after radia- tion therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and pred- nisone (VCP) after XRT in children with untreated, high- stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. Results: Survival and progression-free survival (PFS) 6 SE at 7 years were 55% 6 5% and 54% 6 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% 6 5% versus 45% 6 5%, respectively (P 5 .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P 5 .0014; 32% 6 10% v 58% 6 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M21) on PFS was powerful (P 5 .0006); 5-year PFS rates were 70% 6 5%, 57% 6 10%, and 40% 6 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm 2 of residual tumor, versus H 1.5 cm2 of residual tumor by scan, were significantly differ- ent (P 5 .023; 78% 6 6% v 54% 6 11%, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, H 3 years with I 1.5 cm2 residual tumor, had a 78% 6 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate. J Clin Oncol 17:832-845. r 1999 by American Society of Clinical Oncology.