Faculty Bibliography

The authors review their experience with the operative management of 19 consecutive cases of malignant astrocytoma of the spinal cord. There was a male to female ratio of 1.1:1, and the median age of the population was 14 years (range 1 to 32 years). The median duration of symptoms prior to definitive diagnosis was 7 weeks. Radical excision was carried out in all cases, with 18 patients (95%) receiving radiotherapy and 10 patients (53%) receiving chemotherapy as well. To date, 15 (79%) of the 19 patients in this series have died, with a median survival period of 6 months following surgery. No patient improved after operation. Hydrocephalus was present in 11 patients (58%), seven of whom underwent ventricular shunting procedures. Dissemination of disease was found in 11 patients (58%). Extraneural metastases did not occur in the absence of a ventricular shunt. The authors conclude that malignant astrocytomas of the spinal cord are heralded by a short history followed by rapid neurological deterioration and usually death. The rationale for operation is discussed, and an aggressive approach utilizing adjuvant therapy directed at the entire neuraxis is suggested

Intravenous high-dose methotrexate (HD-MTX) reduces cerebral glucose metabolism and produces behavioral abnormalities and electroencephalographic slowing in an animal model of acute HD-MTX neurotoxicity and in cancer patients undergoing HD-MTX chemotherapy. We used our model of HD-MTX neurotoxicity in the rat to determine if leucovorin (5-formyltetrahydrofolate) reduces this neurotoxicity, and extended our characterization of this model to identify regional as well as global HD-MTX treatment effects and to investigate HD-MTX-induced alterations in regional brain pH. Intravenous high-dose leucovorin reversed the HD-MTX-induced decrease in cerebral glucose metabolism and associated behavioral and electroencephalographic abnormalities in the rat, but low-dose leucovorin was ineffective. The major effect of HD-MTX on cerebral glucose metabolism was a global reduction; however, smaller region-specific treatment effects were identified in auditory, thalamic, and white matter structures. HD-MTX did not alter regional brain pH. These findings suggest a potential clinical role for high-dose leucovorin in severe or prolonged acute HD-MTX neurotoxicity and provide an important justification for the role of positron emission tomography in the early detection of clinical HD-MTX neurotoxicity

Thirty-three patients were treated with intravenous (IV) cisplatin (CPDD) of whom 32 were considered evaluable. There were 14 medulloblastomas, five primitive neuroectodermal tumors (PNET), nine gliomas, three ependymomas, and one germ cell tumor. The overall response rate was 13 of 32 (41%). Eleven responses (five complete [CR], five partial [PR], one mixed [MR]) were noted in the patients with medulloblastoma. The response rate within this group was 79%. Toxicity was tolerable, although it precluded further therapy in five patients.

Although high-dose intravenous (IV) methotrexate (MTX) with leucovorin rescue (HDMTX) is effective for certain recurrent primary brain tumors, concern for inducing leukoencephalopathy has restrained its use as adjuvant therapy following therapeutic brain irradiation (RT). We have conducted a phase I to II clinical trial using four biweekly courses of HDMTX (8 g/m2) in a neoadjuvant setting in ten patients with newly diagnosed high-risk pediatric primary brain tumors. Four patients experienced an objective response after two to four courses of HDMTX alone (medulloblastoma, one; pineoblastoma, one; malignant cerebral astrocytoma, two). All ten patients subsequently received a course of therapeutic RT, and in seven cases, adjuvant chemotherapy with other agents. One patient acquired an acute transient encephalopathy before RT that completely resolved, and another developed a seizure disorder following RT associated with white matter abnormalities on a magnetic resonance imaging (MRI) scan. Five patients have survived a minimum of 33+ months, and four remain in continuous remission. The acute and delayed neurotoxicity of neoadjuvant HDMTX is acceptable, and we favor further use of this neoadjuvant approach in the context of a phase III trial

From 1977 to 1986, 50 children aged 15 months to 18 years were treated for supratentorial malignant gliomas at the Memorial Sloan-Kettering Cancer Center and the New York University Medical Center. Thirteen patients had glioblastoma multiforme, 29 had anaplastic astrocytomas, and 8 had malignant gliomas. In 10 patients the tumor evolved from a low-grade lesion. Seven patients, including 2 patients with neurofibromatosis, developed multiple primary malignant neoplasms. The median time to tumor progression after surgery was 31 weeks, with local recurrence representing the mode of treatment failure in nearly all patients. Notable clinical features included symptomatic leptomeningeal metastasis (13 patients) and intratumoral hemorrhage (9 patients). The estimated median survival time for all 50 patients was 98 weeks, with a 3-year survival rate of 32%. A trend toward longer survival was seen in patients 12 years of age or younger at diagnosis. There was no apparent correlation between survival and tumor histology or tumor location. Recommendations for management are presented