Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.

Radiation therapy for incompletely resected meningiomas.

Twelve patients with incompletely resected meningiomas were treated with postoperative radiation therapy. Nine of these patients had previously undergone incomplete surgical resection, and three had suffered one or more postoperative recurrences. The median dose of irradiation was 5490 rads in 6 weeks (range 4800 to 6080 rads). All patients were followed with serial neurological examinations and computerized tomography (CT) scans. Median follow-up period was 54 1/2 months (range 20 to 120 months); 10 of the 12 patients were followed for longer than 42 months posttreatment. Nine patients had no clinical evidence of recurrent disease after radiation therapy, and CT scans confirmed lack of progression or a gradual decrease in tumor size. Three patients had tumor recurrences; two of these lesions appeared at 70 and 112 months after irradiation as extracranial extensions beyond the margin of the irradiation field, and one has exhibited recurrence within the field at 48 months. Three patients who were treated after prior recurrences have demonstrated prolonged progression-free intervals in comparison to the intervals between recurrences prior to irradiation. No significant complications attributable to treatment have been found in any of the patients. These results are discussed in relation to previous reports of the incidence of meningioma recurrence after incomplete resection.