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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. Lel 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
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; Doernbecher Children's
Hospital, Portland, OR; Childrens Hospital of Denver, Denver, CO; Department of
Pediatrics, University of Iowa, Iowa City, IA; Cleveland Rainbow Babies
Hospital, Cleveland, OH; and Children's National Medical Center, Washington, DC.
Address reprint requests to Paul M. Zeltzer, MD, Children's
Cancer Group, PO Box 60012, Arcadia, CA 91066-6012.
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.
© 1999 American
Society for Clinical Oncology
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