Faculty Bibliography

A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen

Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission

Complications of chemotherapy in pediatric brain tumor patients tend to be acute and short-lived with some special exceptions such as permanent hearing impairment secondary to cisplatin, infertility and an increased risk of second primary neoplasms. Chemotherapy will be better tolerated and probably more effective in brain tumor patients following a major surgical resection, especially when agents such as cisplatin and cyclophosphamide are administered which require intensive intravenous hydration. Neoadjuvant or pre-radiotherapy chemotherapy administration may reduce chemotherapy-related side effects such as leukoencephalopathy secondary to high-dose intravenous methotrexate, neutropenia and thrombocytopenia following intensive chemotherapy, especially when craniospinal radiotherapy is required. The use of bone marrow ablative chemotherapy followed by autologous marrow rescue poses a new spectrum of organ toxicities. New supportive care measures significantly improved tolerance of chemotherapy such as mesna, a drug minimizing hemorrhagic cystitis following ifosfamide, ondonsetron, a highly effective antiemetic, and the hematopoietic growth factors such as G-CSF and GM-CSF which reduce the incidence and severity of symptomatic neutropenia. Chemotherapy may prolong life in patients with recurrent disease and contribute to curative therapy in newly diagnosed patients. The neurooncology community is becoming more familiar with the measures to improve its tolerance and thereby increase its efficacy

Brainstem gliomas, constituting approximately 10% of all childhood central nervous system tumors, remain the most resistant of all brain tumors to therapy. A subgroup of high-risk patients with tumors that diffusely involve the brainstem or that microscopically demonstrate foci of anaplasia on biopsy specimens rarely survive after treatment. Conventional doses of radiotherapy result in temporary clinical improvement in the majority of these high-risk patients; however, few if any remain alive 18 months after treatment. Hyperfractionated radiotherapy, with delivery of larger numbers of smaller fractions of radiotherapy, is a possible way to increase tumor control without increasing neurological toxicity. In 1985, a multiinstitutional phase I/phase II trial, using 100 cGy of radiation therapy twice daily to a total dose of 7,200 cGy, was undertaken for patients with high-risk brainstem gliomas. At the time of writing, 24 (69%) had developed progressive disease and 11 remained in continuous progression-free remission. Actuarial progression-free survival at 20 months is approximately 30%. Twenty-three of 31 evaluable patients had an objective radiographic response to therapy. In comparison to both historical control patients and patients treated in a previous trial using 6,480 cGy of hyperfractionated radiation therapy, there was a statistically significant improvement in progression-free survival rate for patients treated with 7,200 cGy of hyperfractionated radiation therapy (p less than 0.01). To date no patient has died as a result of treatment. Six patients developed transient neurological deterioration or cystic intralesional changes, as demonstrated on magnetic resonance imaging, within 6 weeks of the completion of radiotherapy. Postmortem examination performed in 7 patients did not disclose significant radiation necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

MR scans of 87 pediatric patients with brain stem gliomas were retrospectively reviewed to develop a new classification scheme based on MR imaging. The scheme that has been developed utilizes primarily T2-weighted images, as these most accurately show tumor extent. Tumors are characterized as to location of origin, focality, direction and extent of tumor growth, degree of brain stem enlargement, degree of exophytic growth, and presence or absence of cysts, necrosis, hemorrhage, and hydrocephalus. The use of this classification allowed identification of differences in a population of patients who were selected to be as similar as possible. This system will aid in the assessment of new protocols for treatment of brain stem tumors