Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children's Cancer Group 921 randomized phase III study

Purpose: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an instituti onal diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entr y was 7.0 years, Results: Survival and progression-free survival (PFS) +/- SE at 7 years wer e 55% +/- 5% and 54% +/- 5%, respectively, VCP was superior to 8-in-1 chemo therapy, with 5-year PFS rates of 63% +/- 5% versus 45% +/- 5%, respectivel y (P = .006). Upon central neuropathology review, 188 patients were confirm ed as having MB and were the subjects for analyses of prognostic factors, C hildren aged 1.5 to younger than 3 years had inferior 5-year estimates of P FS, compared with children 3 years old or older (P = .0014; 32% +/- 10% v 5 8% +/- 4% respectively), For MB patients 3 years of age or older, the progn ostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006 ); 5-year PFS rates were 70% +/- 5%, 57% +/- 10%, and 40% +/- 8%, respectiv ely. PFS distributions at 5 years for patients with MO tumors with less tha n 1.5 cm(2) of residual tumor, versus greater than or equal to 1.5 cm2 of r esidual tumor by scan, were significantly different (P = .023; 78% +/- 6% v 54% +/- 11%, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8 -in-1 chemotherapy plus XRT. For patients with MO tumors, residual tumor bu lk (nor extent of resection) is a predictor for PFS, patients with MO tumor s, greater than or equal to 3 years with less than or equal to 1.5 cm(2) re sidual tumor, had a 78% +/- 6% 5-year PFS rate. Children younger than 3 yea rs old who received a reduced XRT dosage had the lowest survival rate. (C) 1999 by American Society of Clinical Oncology.