Efficacy of irradiation for incompletely excised acoustic neurilemomas.

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.

Radiation therapy in the treatment of partially resected meningiomas.

To address the question of whether radiation therapy is beneficial in the management of partially resected meningiomas, we reviewed the records of all patients admitted to the University of California, San Francisco, between 1968 and 1978 who had a diagnosis of intracranial meningioma. The patients were divided into three groups: 51 patients had gross total resection and did not receive radiation therapy, 30 patients had subtotal resection and no radiation therapy, and 54 patients had subtotal resection followed by radiation therapy. The subtotal resection groups were similar in average age, male:female ratio, and tumor location, which allowed a valid comparison of the effects of irradiation. The recurrence rate in the total resection group was 4% (2 of 51 patients). Among patients in the subtotal resection groups, 60% of nonirradiated patients had a recurrence, compared with only 32% of the irradiated patients. The median time to recurrence was significantly longer in the irradiated group than in the nonirradiated group (125 vs. 66 months, P less than 0.05). There was no complication related to irradiation. These results provide convincing evidence that radiation therapy is beneficial in the treatment of partially resected meningiomas.

Intraspinal tumors in children.

Thirty cases of intraspinal neoplasms occurring during the first two decades of life are reviewed. Histologic examination showed 13 of these to be astrocytomas, 6 neuroblastomas, 5 sarcomas, 3 ependymomas, 2 neurofibromas and 1 a schwannoma. Orthopedic deformities developed or worsened in 60 percent of patients surviving longer than a year after diagnosis. In five patients some form of endocrine deficiency developed after irradiation. For treatment of radiosensitive extradural malignant lesions, biopsy followed by irradiation is advocated.

BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors.

Twenty-nine patients with recurrent malignant brain tumors were evaluated. BCNU (180 mg/m2) was administered iv on Day 1 and 5-fluorouracil (1 g/m2/day) was given by continuous infusion on Days 15--17. Courses were repeated every 6 weeks until tumor progression occurred. Before each course, a neurologic examination and radionuclide and computerized tomographic scans were performed. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Nine of 29 patients (31%) responded to therapy, five of 29 (17%) showed progression, and 15 of 29 (52%) had disease stability. The estimated median time to progression was 27 weeks for all patients, 34 weeks for the response group, and 25 weeks for the stable group. Of all 29 patients, 24 (83%) had tumor progression arrested; 40% with response and 6% with stable disease were continuing therapy after 1 year. The stable disease group was larger and the duration of stability was longer than that seen in previous studies. Evaluated by time to progression, a BCNU-5-fluorouracil combination is superior to either BCNU alone or a BCNU-procarbazine combination.

Single-agent chemotherapy of brain tumors. A five-year review.

Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug.

The treatment of meningiomas in childhood.

Thirteen cases of meningiomas in the pediatric age group seen at the University of California are reviewed. Four of these patients are alive; one had complete surgical resection of tumor and three had subtotal resection followed by irradiation, with total tumor doses of 4500 to 5500 rads. On the basis of these data, together with our total experience in the treatment of 188 patients with meningiomas, we conclude that patients who have complete surgical resection need no further treatment but patients who have subtotal removal may have recurrences delayed or prevented by the addition of postoperative irradiation to their therapeutic regimens.

BCNU (NSC-409962) and procarbazine (NSC-77213) treatment for malignant brain tumors.

Sixty-five patients with malignant brain tumors were treated with a combination of BCNU (100 mg/m2 qd X 1) and procarbazine (100 mg/m2 qd X 14); the cycle was repeated in 1 month and then on a 6-week schedule with procarbazine being given for 21 days. Forty-five patients had malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma, malignant glioma, or gemistocytic astrocytoma) and were evaluated as a group. All patients had either shown evidence of tumor regrowth after previous surgery and/or radiotherapy, or had deep unbiopsied tumors presumed to be malignant gliomas. Of these 45 patients, 13 of 45 (30%) were judged to be unequivocal responders and an additional eight of 45 (17%) were designated as probable responders. The median duration of clinical response was 34 weeks for responders and 20 weeks for probable responders. The combination of BCNU and procarbazine, therefore, was somewhat inferior to a previous combination of procarbazine, CCNU, and vincristine.

Long-term survival of patients treated with BCNU for brain tumors.

The authors present three patients who, after excision and irradiation of their brain tumors, were treated with BCNU for recurrence. All three patients responded well and now are without evidence of tumor, 37, 30, and 36 months after BCNU was stopped. Although these patients represent only a small fraction of those treated with BCNU, they indicate the potential role of chemotherapy in the management of glial tumors.

The role of radiation therapy in the treatment of astrocytomas.

One hundred forty-seven patients with astrocytoma were treated between 1942 and 1967. There were 25 postoperative deaths. The 14 patients in whom the tumor was thought tohave been completely removed were not irradiated and all survived 5 years or longer. Seventy-one of the 108 patients with imcompletely excised lesions received radiation therapy. The 5-year survival rate for those with imcomplete resection alone was 19%, compared to 46% when irradiation was given. Based on observations up to 20 years, after incomplete removal postoperative irradiation significally prolonged useful life and may have lead to permanent control in some. There was no evidence of radiation damage. Most of these tumors were fibrillary astrocytomas, and the results apply particularly to this histologic type. Only 1 of 11 patients with gemistocytic astrocytoma survivied 5 years. The survival rate for Grade i tumors was appreciably greater than for Grade iilesions; in both grades, it was improved by irradiation.

Phase II study of procarbazine, CCNU, and vincristine combination chemotherapy in the treatment of malignant brain tumors.

Forty-eight patients with primary or metastatic malignant tumors of the central nervous system (CNS) were treated with combination chemotherapy, consisting or procarbazine (100 mg/m2 X 14 days), CCNU (75 mg/m2), and vincristine (1.4 mg/m2 X 2, 1 week apart) (PCV) every 4 weeks. Most patients had undergone initial resection of primary tumors, postoperative radiotherapy, and a post irradiation interval of 3 months or more. Other patients harbored unbiopsied, newly-discovered primary or metastatic tumors. All patients were deteriorating neurologically when treatment began. Overall response rate for PCV combination therapy was 44%, no better than results obtained with single agent procarbazine or BCNU, the most effective drugs used alone in previous brain tumor chemotherapy studies.