Preradiation chemotherapy for pediatric patients with high-grade glioma

Abstract

Background: To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported.

Methods: Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation.

Results: The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of > or = 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of > or = 90% (P = 0.003), irradiation with > or = 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006).

Conclusions: These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection.