Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A childrens cancer group phase 1/11 trial

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Abstract
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.