Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: A pediatric oncology group study

Purpose: In September 1984, the Pediatric Oncology Group began accrual to a Phase I/II study designed to assess the efficacy and toxicity of sequentially escalated doses of hyperfractionated (twice daily) radiotherapy in children wit-h poor-prognosis brain stem tumors. Pediatric Oncology Group Study #849closed in June 1990 with a total of 136 patients on study. We report here the outcome of patients treated atthe third and final dose level (75.6 Gy), and compare the results to those obtained at the 66 and 70.2 Gy dose levels. Methods and Materials: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the midbrain, pons or medulla. Histological confirmation of diagnosis was not mandatory provided that the clinical and radiological findings were typical for brain stem glioma. Treatment consisted of radiotherapy delivered to local fields. At the third dose level, fraction sizes of 1.26 Gy were given twice dally, with a minimum interfraction interval of 6 hr to a dose of 75.6 Gy in 60 fractions over 6 weeks. Between 5 89 and 6 90, 41 patients were accrued to the study. Two were excluded from analysis leaving 39 evaluable patients, 21 male and 19 female, whose ages ranged from 3 to 15 years (median 7.5 years). Results: Following treatment, neurological improvement was reported in 30/39 (77%) of the patients. On central review of imaging studies in 29 patients, one patient was found to have had a complete response to radiotherapy, five a partial (> 50% response), and only three had non-responding or progressive disease. The median time to disease progression was 7 months; median survival time was 10 months; survival at 1 year was 39.9% (SE 8.3%) and at 2 years, 7% (SE 4.8%). The pattern of failure was local in all patients; in addition six had evidence of leptomeningeal seeding. Morbidity of treatment included an enhanced skin reaction (21%), otitis media and/or externa (26%) and steroid use > 3 months (62%). Intralesional necrosis was a frequent finding (45%) on imaging studies performed at a median time of 6 weeks post treatment. Conclusion: The results of treatment in terms of progression-free survival and overall survival are not significantly different (at p = .55 and p = .46, respectively) from those obtained at the two previous dose levels. There is no evidence that higher doses of hyperfractionated radiotherapy given as in this study improve the outlook of patients with poor-risk brain stem gliomas.