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

Author:

Zeltzer Paul M.1,Boyett James M.1,Finlay Jonathan L.1,Albright A. Lel1,Rorke Lucy B.1,Milstein Jerrold M.1,Allen Jeffrey C.1,Stevens Kenneth R.1,Stanley Philip1,Li Hao1,Wisoff Jeffrey H.1,Geyer J. Russell1,McGuire-Cullen Patsy1,Stehbens James A.1,Shurin Susan B.1,Packer Roger J.1

Affiliation:

1. From the University of California at Irvine Medical Center, Orange, Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, and Childrens Hospital, Los Angeles, CA; St. Jude Children's Research Hospital, Memphis, TN; Memorial Sloan-Kettering Cancer Center, Beth Israel Medical Center, and New York University Medical Center, New York, NY; Children's Hospital of Pittsburgh, Pittsburgh, and Children's Hospital of Philadelphia, Philadelphia, PA; Children's Hospital and Medical Center, Seattle, WA;...

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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