Faculty Bibliography

Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has a more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m2) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed a local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC

Three children had central nervous system tumors with histologic and ultrastructural features corresponding to those of tumors previously described as 'gliofibromas.' These features, which include a composite appearance with glial and mesenchymal elements, with glial fibrillary acidic protein (GFAP)-containing and GFAP-immunonegative cells, diffuse S-100 immunoreactivity, and basal lamina wrapping processes of both cell types, suggest that the 'mesenchymal' cells are Schwann cells, not fibroblasts. We therefore propose to rename this entity 'glioneurofibroma.' The clinical behavior of these lesions is uncertain but is more often indolent or benign

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

The management of patients with primary intracranial germ cell tumors is evolving. There is attention to minimizing late effects of therapy and preserving curability in those patients with pure germinomas and in intensifying chemotherapy for patients with nongerminoma germ cell tumors in an attempt to prolong disease-free survival.

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