A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

SUMMARYThe possibility that cerebral ischemia may initiate a series of pathological free radical reactions within the membrane components of the CNS was investigated in the cat. The normally occurring electron transport radicals require adequate molecular oxygen for orderly transport of electrons and protons. A decrease in tissue oxygen removes the controls over the electron transport radicals, and allows them to initiate pathologic radical reactions among cell membranes such as mitochondria. Pathologic radical reactions result in multiple products, each of which may be present in too small a concentration to permit their detection at early time periods. It is possible to follow the time course, however, by the decrease of a major antioxidant as it is consumed by the pathologic radical reactions. For this reason, ascorbic acid was measured in ischemic and control brain following middle cerebral artery occlusion. There was a progressive decrease in the amount of detectable ascorbic acid ranging from 25% at 1 hour to 65% at 24 hours after occlusion. The reduction of this normally occurring antioxidant and free radical scavenger may indicate consumption of ascorbic acid in an attempt to quench pathologic free radical reactions occurring within the components of cytomembranes.

No abstract

The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and June 30, 1990, were retrospectively reviewed in order to determine long-term survival, event-free survival, and functional outcome resulting after radical resection and to assess the impact of histological grading on outcome. Tumors were located in the cerebral hemisphere in 19 cases, the spinal cord in 30, and the brain stem in nine. Forty-four patients had gross total resection and 14 had radical subtotal resection. Only six patients underwent postoperative irradiation or chemotherapy and, therefore, the outcome was generally related to surgery alone. Of the 58 gangliogliomas, 40 were classified as histological grade I, 16 were grade II, and two were grade III. The median follow-up period was 56 months. There were no operative deaths, and the operative morbidity rate was 5%, 37%, and 33% for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas, respectively. The 5-year actuarial survival rates for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas were 93%, 84%, and 73%, respectively (p = 0.7). The event-free survival rate at 5 years was 95% for cerebral hemisphere gangliogliomas and 36% for spinal cord gangliogliomas (p < 0.05); for brain-stem gangliogliomas the event-free survival rate at 3 years was 53% (p < 0.05). Neurological function at recent follow-up evaluation was stable or improved in 81% of patients. Multivariate analysis (Cox linear regression) revealed tumor location to be the only variable predictive of outcome, with spinal cord and brain-stem gangliogliomas having a 3.5- and 5-fold increased relative risk of recurrence, respectively, compared to cerebral hemisphere gangliogliomas. Histological grade was not predictive of outcome, although in each location there was a trend for higher-grade tumors to have a shorter time to recurrence. It is concluded that radical surgery leads to long-term survival of patients with gangliogliomas, regardless of location, and adjuvant therapy can probably be reserved for special cases.