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.