Harry S. Greenberg

Eighty-three patients with epidural spinal cord compression, from metastatic cancer were treated with high-dose adrenocorticosteroids and a new radiation fractionation protocol. Only those patients were included who had complete or almost complete block on myelography and who had not received prior radiation therapy to the area of compression. Patients were given 100 mg of dexamethasone intravenously at the time of diagnosis and 500 rads of radiation on each of the first three days. After a four-day rest, radiation therapy was continued at 300 rads to a total dose of 3,000 rads. The effects of this new protocol on the patient's motor abilities did not differ from those of previous protocols, namely, 47 of 83 patients (57%) were ambulatory after treatment, with no responses in patients totally paraplegic before treatment. However, early administration of high doses of dexamethasone substantially ameliorated pain in the majority of patients, with relief often coming within hours after the drug was given. On the basis of these data, we recommend high doses of adrenocorticosteroids combined with radiation therapy for acute treatment of spinal cord compression. The optimum fractionation schedule for radiation therapy is not established.

We studied 43 patients with metastases to the base of the skull to determine whether clinical symptoms localized the lesions accurately. We identified five clinical syndromes: orbital, parasellar, middle fossa, jugular foramen, and occipital condyle. The orbital and parasellar syndromes were characterized by frontal headache, diplopia, and first-division trigeminal sensory loss. Proptosis occurred with the orbital but not the parasellar syndrome. The middle-fossa syndrome was characterized by facial pain or numbness. The jugular foramen syndrome was characterized by hoarseness and dysphagia, with paralysis of the ninth through eleventh cranial nerves. The occipital condyle syndrome was characterized by unilateral occipital pain and unilateral tongue paralysis.

The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m(2) i.v. every three weeks in patients not on EIAED and 750 mg/m(2) in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 17.6%. PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.

PURPOSE: The goal of three-dimensional (3-D) conformal radiation is to increase the dose delivered to tumor while minimizing dose to surrounding normal brain. Previously it has been shown that even escalated doses of 70 to 80 Gy have failure patterns that are predominantly local. This article describes the failure patterns and survival seen with high-grade gliomas given 90 Gy using a 3-D conformal intensity-modulated radiation technique. PATIENTS AND METHODS: From April 1996 to April 1999, 34 patients with supratentorial high-grade gliomas were treated to 90 Gy. For those that recurred, failure patterns were defined in terms of percentage of recurrent tumor located within the high-dose region. Recurrences with more than 95% of their volume within the high-dose region were considered central; those with 80% to 95%, 20% to 80%, and less than 20% were considered in-field, marginal, and distant, respectively. RESULTS: The median age was 55 years, and median follow-up was 11.7 months. At time of analysis, 23 (67.6%) of 34 patients had developed radiographic evidence of recurrence. The patterns of failure were 18 (78%) of 23 central, three (13%) of 23 in-field, two (9%) of 23 marginal, and zero (0%) of 23 distant. The median survival was 11.7 months, with 1-year survival of 47.1% and 2-year survival of 12.9%. No significant treatment toxicities were observed. CONCLUSION: Despite dose escalation to 90 Gy, the predominant failure pattern in high-grade gliomas remains local. This suggests that close margins used in highly conformal treatments do not increase the risk of marginal or distant recurrences. Our results indicate that intensification of local radiotherapy with dose escalation is feasible and deserves further evaluation for high-grade gliomas.