Background. Brain stem gliomas remain the childhood brain tumors most resistant to treatment. Treatments with hyperfractionated radiotherapy at doses as high as 7560 cGy have been fairly well tolerated. This study was undertaken to determine the toxicity and possible efficacy of hyperfractionated radiotherapy in children with brain stem gliomas using 100 cGy of radiation twice daily, to a total dose of 7800 cGy. Methods. Sixty‐six children (mean age at diagnosis, 7.5 years) with diffuse intrinsic brain stem gliomas were treated. Patients were evaluated for potential toxicity of treatment, progression‐free survival, survival, and response to treatment. Results. Objective response to treatment was documented in 20 of 58 (34%) evaluable patients, with 8 (14%) patients having a greater than 50% reduction in tumor size. Overall survival was 35% plus or minus 6% at 1 year and 11% plus or minus 6% at 3 years. Intralesional cystic/necrotic radiographic changes developed in nine patients 6 weeks after radiation, and three of these patients subsequently improved without antitumor intervention. Six of 14 autopsied patients had evidence of probable radiation‐induced intralesional necrotic damage, and in 1, necrosis may have played a role in death. Thirty‐three of 66 patients were treated with steroids for prolonged periods. Conclusions. The results of this treatment regimen demonstrate that hyperfractionated radiotherapy, as delivered in this study to a total dose of 7800 cGy, is relatively well tolerated, but may result in prolonged steroiduse dependency and possible radiation‐associated damage. Objective responses to treatment were seen in 34% of patients, but these results were not better than those seen at lower doses of hyperfractionated radiotherapy. There is no evidence that radiation to 7800 cGy results in improved survival for patients with diffuse intrinsic brain stem gliomas.

Background. Most children with brain stem gliomas (BSG) die within 18 months of diagnosis. Early experience suggested that hyperfractionated radiation therapy (RT) at a dose of 72 Gy, administered in 1‐Gy fractions twice daily, possibly improved disease‐free survival for children with BSG. Methods. To better characterize the toxicity and possible efficacy of this dose and fractionation of RT, 53 assessable children with diffuse intrinsic or malignant BSG were treated. Survival figures also were combined with outcome in 36 patients treated in a previous pilot study. Results. An objective response to treatment was observed in 28 of 53 (53%) patients; a partial response occurred in 7. No child died of treatment‐related brain necrosis, although 7 of 53 did have intralesional cystic/necrotic changes within 6 weeks of completion of RT. The overall survival rate for patients in the study was 38% (± 6.5) at 1 year, 14% (± 5.4) at 2 years, and 8% (± 6.5) at 3 years. Leptomeningeal dissemination was observed in 4 of 48 (8%) children who had relapses. A greater than 2‐month duration of symptoms before diagnosis was related to a better prognosis. There was no statistical association between any other clinical parameter, neuroradiographic finding, or pathologic finding and outcome. Combined with that in 35 patients treated in the pilot study, the survival rate in 88 children was 14% (k 5) at 3 years. Conclusions. The radiographic response rate is encouraging; however, it cannot be concluded that hyperfractionated RT, at this dose schedule and total dose, is superior to conventional RT. Cancer 1993; 72:1414‐21.

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