Hyperfractionated radiotherapy in brain stem tumors: results of a Pediatric Oncology Group study

Between September 1984 and January 1986, 38 patients were entered onto the first phase of a Pediatric Oncology Group study designed to test the feasibility of treating children with brain stem tumors with hyperfractioned (twice daily) radiotherapy, to assess the early and late morbidity and efficacy of such treatment, and to test the feasibility of dose escalation in this group of patients. Of the 34 patients considered eligible after neuroradiology review, two did not complete planned radiotherapy because of progressive disease; both died of disease at 4 weeks and 9 months following initiation of treatment. The remainder were treated with 1.1 Gy twice daily, with an interval of 4 to 6 hours, to a total dose of 66 Gy in 60 fractions over 6 weeks. The majority of patients (24/34, 71%) improved clinically during the course of treatment; two remained stable, seven deteriorated, and for one the clinical response was unknown. By CT scan and/or MRI, no patient showed complete regression of disease; five showed a partial response to treatment, twenty fell into a stable disease category, eight patients developed progressive disease by the time of their first follow-up radiologic examination, and one patient was not evaluable for response, having been lost to follow-up immediately after completion of treatment. All five patients who achieved partial response and 17/20 patients in the stable, disease category subsequently progressed, after a median interval of 6.5 months. The median survival time was 11 months and survival at 1 year was 48% (SE 0.08). Morbidity of treatment consisted of an enhanced skin reaction in three patients, otitis media and/or externa in nine, and complications related to steroid intake in four, including diabetic ketoacidosis (two patients), Pneumocystis pneumonia (one patient), and disseminated varicella (one patient). Protracted use of steroids in 13 patients was associated in all instances with non responding or progressive disease. No patient developed signs or symptoms suggestive of CNS damage, and tissue obtained by biopsy at the time of progression in three patients and at autopsy in five failed to demonstrate any evidence of injury attributable to the radiotherapy. A dose escalation to 70.2 Gy in 60 fractions over 6 weeks was implemented as planned.