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

Paul M. Zeltzer, James M. Boyett, Jonathan L. Finlay, A. Leland Albright, Lucy B. Rorke, Jerrold M. Milstein, Jeffrey C. Allen, Kenneth R. Stevens, Philip Stanley, Hao Li, Jeffrey H. Wisoff, J. Russell Geyer, Patsy McGuire-Cullen, James A. Stehbens, Susan B. Shurin, Roger J. Packer

Research output: Contribution to journalArticle

543 Scopus citations

Abstract

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 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) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .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 = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic 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%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus ≥ 1.5 cm2 of residual 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 M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

Original languageEnglish (US)
Pages (from-to)832-845
Number of pages14
JournalJournal of Clinical Oncology
Volume17
Issue number3
StatePublished - Mar 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zeltzer, P. M., Boyett, J. M., Finlay, J. L., Albright, A. L., Rorke, L. B., Milstein, J. M., Allen, J. C., Stevens, K. R., Stanley, P., Li, H., Wisoff, J. H., Geyer, J. R., McGuire-Cullen, P., Stehbens, J. A., Shurin, S. B., & Packer, R. J. (1999). 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. Journal of Clinical Oncology, 17(3), 832-845.