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Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) for small, localized, pediatric brain tumors and to determine the patterns of failure., Methods and Materials: A total of 81 patients were enrolled in an institutional review board-approved prospective Dana-Farber Cancer Institute protocol between 1992 and 1998. Of the 81 patients, 50 had low-grade astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior fossa ependymoma, and 4 had other histologic types. All patients underwent biopsy for diagnosis, with the exception of patients with neurofibromatosis and radiographic evidence of an optic system tumor. The neurocognitive outcome for all patients was also an endpoint of the study and will be reported separately. This report focused on the patients with low-grade gliomas only. Of the 50 patients, 26 were males and 24 females; the median age was 9 years (range, 2-26 years). The indications for treatment of patients with low-grade gliomas were progression during or after chemotherapy or progression after surgery alone. SRT was delivered using a dedicated 6-MV linear accelerator. Immobilization was accomplished with a removable head-frame. CT and MRI fusion was used for treatment planning. The target volume generally included the preoperative tumor plus a 2-mm margin for the planning target volume. The median collimator size was 47.25 mm (range, 30-60 mm). Three to nine arcs were used to deliver a mean total dose of 52.2 Gy in 1.8-Gy daily fractions., Results: With a median follow-up of 6.9 years (range, 0.9-10.2 years), the progression-free survival rate was 82.5% at 5 years and 65% at 8 years. The overall survival was 97.8% at 5 years and 82% at 8 years. Six patients had local progression. Two of the patients with local progression had pathologic progression to anaplastic astrocytoma 3 and 7 years after initial SRT. Five patients, all with optic system/hypothalamic primary tumors, developed central nervous system dissemination 1.0-7.4 years after SRT. One patient developed a presumed radiation-induced primitive neuroectodermal tumor 6 years after initial treatment. Six patients died, three of dissemination, two of progression to higher grade tumors, and one of a secondary radiation-induced tumor. All 6 cases of local progression were within the primary tumor bed at the time of progression and had received the full prescription dose. No marginal failures occurred., Conclusion: Stereotactic radiotherapy provides excellent local control for children with small, localized low-grade glial tumors. Marginal failures have not been observed, supporting the use of limited margins to minimize late sequelae using stereotactic immobilization and planning techniques.

Purpose: To determine the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brainstem glioma., Methods and Materials: Eighteen patients with brainstem glioma were treated with etanidazole and HRT on a dose escalation protocol (Phase I trial) between 1990 and 1996. All patients had MRI confirmation of diffuse pontine glioma and signs/symptoms of cranial nerve deficit, ataxia, or long tract signs of <6 months' duration. Cervicomedullary tumors were excluded. Patients (median age: 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2-cm margin with parallel-opposed 6-15-MV photons. The total dose was 66 Gy in 44 fractions (1.5 Gy b.i.d., with at least 6 h between fractions) for the first 3 patients and 63 Gy in 42 fractions for the subsequent 15 patients. Etanidazole was administered as a rapid i.v. infusion 30 min before the morning fraction of HRT. Planned doses of etanidazole were 1.8 g/m(2) x 17 doses (30.6 g/m(2)) at Step 1 to a maximum of 2.4 g/m(2) x 21 doses (50.4 g/m(2)) at Step 8. Dose escalation was planned with 3 patients at each of the 8 levels., Results: Three patients were treated at each dose level except Level 2, on which only 1 patient was treated. The highest dose level achieved was Level 7, which delivered a total etanidazole dose of 46.2 g/m(2). Two patients were treated at this level, and both patients experienced Grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 g/m(2) (dose Level 6) without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 23 cases of Grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 weight loss, 3 others), 11 cases of Grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthralgia, 1 urinary retention, 1 hematologic), and 4 Grade 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral neuropathy was not seen at any dose level. The median survival from the start of treatment was 8.5 months (range: 3-58 months)., Conclusion: The MTD of etanidazole in children receiving HRT for brainstem glioma is 42 g/m(2), with cutaneous rash as the dose-limiting toxicity. This is in contrast to the adult experience, which demonstrates a 24% lower MTD of 34 g/m(2) limited by peripheral neuropathy.

Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation., Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients., Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients., Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.