Hyperfractionated radiotherapy for diffuse intrinsic brain stem tumors in children

Over the past decade, the principal focus of clinical research in children with diffuse intrinsic brain stem tumors has been on the use of hyperfractionated radiotherapy because of the predominantly local pattern of failure and the evidence for a dose-response relationship with conventional radiotherapy that might suggest an advantage to the use of the higher total radiation doses that can be given using a hyperfractionated schedule. Since 1984, large numbers of children have been accrued to a series of phase I/II studies testing escalating doses of hyperfractionated radiotherapy. At the lowest dose levels of 64.8 and 66 Gy, results were not better than those seen after conventional treatment and no unusual or unexpected toxicity was observed. At intermediate dose levels of 70.2 and 72 Gy there was some suggestion of improved efficacy. At the highest dose level of 75.6 and 78 Gy there were no further gains in efficacy and complications of treatment including steroid dependency and intralesional necrosis were observed with greater frequency. The intermediate dose level was therefore considered to be associated with the best therapeutic ratio and the value of hyperfractionated radiotherapy at this dose level is being tested by the Pediatric Oncology Group in a randomized phase III study that will be completed soon.