Chemotherapy for brain stem gliomas

Approximately 80% of tumors arising in the brain stem are diffuse intrinsic lesions. Patients typically present with a short duration of symptoms and signs with significant neurological impairment. Imaging findings are typical, and biopsy is not usually necessary to make a diagnosis. Standard treatment consists of radiotherapy alone. Although the majority of patients will show a significant improvement in neurological status following such treatment, the prognosis is very poor. The median time to disease progression is of the order of 5-6 months, the median survival time less than 1 year, and survival at 2 years and beyond, less than 10%. Over the last 10-15 years, numerous studies have been undertaken in an attempt to develop more effective treatment for children with diffuse intrinsic brain stem tumors. Using a hyperfractionated (twice-daily) schedule, doses of radiotherapy as high as 78 Gy have been given without success. Other approaches use chemotherapy combined with radiotherapy in a variety of different ways, including up-front, concurrent, and adjuvant chemotherapy, and high-dose chemotherapy with rescue. The results of these studies using chemotherapy, as well as other approaches using other systemic agents, are reviewed in detail.