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Background: The current study was conducted to determine whether the addition of interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine (BCNU) improves time to disease progression or overall survival in patients with high-grade glioma., Methods: Patients with anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation therapy plus BCNU as initial therapy. Subsequently, patients without tumor progression at the completion of radiation therapy were stratified by age, extent of surgery, tumor grade and histology, Eastern Cooperative Oncology Group performance status, and treating institution, and then were randomly assigned to receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3) plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks for a maximum of 6 cycles., Results: Of the 383 patients enrolled in the study, 275 eligible patients were randomized. There was no significant difference with regard to time to disease progression or overall survival between the two groups. Patients receiving IFN-alpha experienced more fever, chills, myalgias, and neurocortical symptoms including somnolence, confusion, and exacerbation of neurologic deficits. Cox multivariate regression models confirmed known favorable prognostic variables including younger age, Grade 3 tumor (according to World Health Organization criteria), and greater extent of surgery. Cox and classification and regression tree analysis models also demonstrated that a normal baseline Folstein mini-mental status examination (MMSE) score was associated with better prognosis., Conclusions: IFN-alpha does not appear to improve time to disease progression or overall survival in patients with high-grade glioma and appears to add significantly to toxicity. The baseline MMSE score may serve as an independent prognostic factor and warrants further investigation., (Copyright 2001 American Cancer Society.)

Object: The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years., Methods: Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02)., Conclusions: It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.

Background: Patients with recurrent intracranial ependymomas were evaluated to assess local control, overall survival, and complications from stereotactic radiosurgery (SRS)., Methods: Twelve patients (with a total of 17 tumors) with recurrent ependymoma underwent SRS. Local failure was defined as tumor progression within the prescription isodose volume, and marginal failure was defined as tumor progression adjacent to the SRS prescription isodose volume. Tumor progression away from the prescription volume was considered distant failure. Eleven of the 12 patients had undergone previous resection and external beam radiation therapy (46-56 Grays [Gy]; median, 54 Gy) before radiosurgery, and 1 patient had failure after complete resection alone. Age at SRS ranged from 5-56 years (median, 29 years). Three patients were female. The marginal tumor dose was 12-24 Gy (median, 18 Gy). One to 14 isocenters (median, 4 isocenters) were utilized to irradiate volumes of 0.3-15.5 cm(3) (median, 3.2 cm(3))., Results: The duration of follow-up ranged from 2.5-60 months (median, 22.5 months). The median overall survival after SRS was 3.4 years (range, 1.4-5 years). In-field local control was achieved in 14 of the 17 tumor sites and estimated 3-year local control was 68%. There were two in-field failures and one marginal failure. Distant failure occurred in two patients. Two patients developed treatment-related complications after SRS., Conclusions: SRS provides good local tumor control for patients with recurrent intracranial ependymoma and may have a favorable impact on survival. SRS should be evaluated more extensively in the initial treatment of patients with ependymoma to minimize local failure after surgical management., (Copyright 2000 American Cancer Society.)

Objective: A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas., Methods: Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3., Results: Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation., Conclusion: This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.

Objective: To review the results and expectations of contemporary stereotactic radiosurgery., Material and Methods: We conducted a retrospective analysis of 1,033 consecutive patients who underwent gamma knife radiosurgery at Mayo Clinic Rochester between January 1990 and January 1998., Results: The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. Of 97 patients with arteriovenous malformations who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of the vascular malformation. Of 209 patients who underwent radiosurgery for benign tumors (schwannomas, meningiomas, or pituitary adenomas) and had radiologic studies after 2 years or more of follow-up, tumor growth control was noted in 200 (96%). Tumor growth was also controlled in 90% of brain metastatic lesions at a median of 7 months after radiosurgery. Of 20 patients with trigeminal neuralgia and follow-up for more than 2 months, 14 (70%) were free of pain after radiosurgery., Conclusion: Radiosurgery is a safe and effective management strategy for a wide variety of intracranial disorders. Use of radiosurgical treatment should continue to increase as more data become available on the long-term results of this procedure.

Purpose: This analysis was performed to examine the outcome of patients with histologically confirmed ependymomas of the brain or spinal cord who received postoperative radiotherapy., Methods and Materials: Eighty patients with histologically confirmed ependymomas were evaluated retrospectively. All were treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up ranged from 5 to 30 years (median 10.4 years)., Results: The 5- and 10-year survival rates for the entire study group were 79% and 73%, respectively. Patients with low-grade (1 and 2 of 4) tumors had a 5-year survival rate of 87% as compared to 27% for those with high-grade (3 and 4 of 4) tumors (p < 0.0001). Patients with tumors of the spine had a 5-year survival rate of 97% as compared to 68% for those with infratentorial tumors, and 62% for those with supratentorial tumors (p = 0.03). Patients with myxopapillary ependymomas of the spine had a 5-year survival rate of 100% as compared with 76% for patients with other histological subtypes of ependymoma (p = 0.02). Multivariate analysis revealed that the survival rate was independently associated with tumor grade (p = 0.0007) and histological subtype (p = 0.02). Twenty-eight patients (35%) experienced local failure and 10 patients (13%) developed leptomeningeal seeding. The 5-year leptomeningeal failure rate was 10% in patients with low-grade tumors as compared to 41% for patients with high grade tumors (p = 0.01)., Conclusion: Patients with low-grade tumors, especially those with myxopapillary subtypes, have high 5-year survival rates when treated with post-operative radiotherapy. High grade ependymomas are associated with a much poorer outcome. New forms of therapy are required to improve the outcome of patients with high-grade ependymomas.

Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done., Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m2 days 1-3, cisplatin 30 mg/m2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m2 every 8 weeks x 4 cycles was given after radiation therapy., Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m2 days 1-3, cisplatin 20 mg/m2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 microg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean +/- SD 2 hr and 6 hr plasma concentrations were 0.92 +/- 0.43 microg/ml and 0.36 +/- 0.12 microg/ml, respectively. Estimated duration of exposure to >0.1 microg/ml etoposide was 10-17 hr., Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.

Objective: This analysis was performed to examine the outcome of adult and pediatric patients with brainstem tumors., Methods and Materials: Forty patients with brainstem glioma were evaluated retrospectively. Included were 24 females and 16 males ranging in age from 3 to 81 years (median, 29.5 years). These patients were treated with various combinations of surgery, chemotherapy, and radiotherapy (RT). The length of follow-up in survivors ranged from 0.6 to 20 years (median: 3.2 years, mean: 6 years). Survival rates were calculated with the Kaplan Meier method and differences between survival curves were calculated using the log-rank test., Results: The overall 2 and 5-year survival rates were 44% and 34%, respectively. The median survival time was 19 months. The 5-year survival rate was 54% for patients with tumors outside the pons compared to 21% for those with tumors involving the pons (p = 0.04). The 5-year survival rate was 59% for patients with exophytic tumors as compared to 23% for those with intrinsic tumors (p = 0.05). Patients undergoing subtotal resection had a 5-year survival rate of 53% compared to 28% for those having only a biopsy or no surgical intervention (p = 0.04). None of the other potential prognostic or treatment related factors evaluated [patient age, tumor grade, tumor histology, radiotherapy parameters (including BID fractionation, 3-D treatment planning, or the use of doses > 55 Gy), or the administration of adjuvant chemotherapy] evaluated were associated with patient survival., Conclusions: Brainstem gliomas generally occur in younger individuals. The survival rates were better for patients with exophytic tumors, those involving sites other than the pons, and tumors amenable to subtotal resection. Improvements in the outcome of patients with brainstem gliomas will require new therapeutic approaches.

Purpose: A Phase I study to determine the safety, toxicity, and maximum tolerated dose (MTD) of carmustine (BCNU) and interferon alpha-2a (IFN-a) when combined with radiation as initial therapy in high-grade glioma., Methods and Materials: Patients with newly diagnosed Grade 3 or 4 astrocytoma, oligoastrocytoma, or gliosarcoma were enrolled after surgery. All received radiation therapy to the brain (64.8 Gy/36 fractions), combined with a single dose of BCNU (200 mg/m2) at the start of radiation. Chemotherapy after completing radiation consisted of BCNU 150 mg/m2 once every 7 weeks, and IFN-a 12 x 10(6) units/m2 subcutaneously Days 1-3 each week of a 7-week cycle. Subsequent dose modification was based on constitutional symptoms for IFN-a and on myelosuppression for BCNU., Results: Fifteen patients were entered on the study. Four were excluded because they did not receive IFN-a (3 refused treatment and 1 patient left the study due to multiple medical problems). Eleven were evaluable for toxicity and efficacy. Nonhematological toxicity, mainly lethargy and flu-like symptoms, were dose-limiting for IFN-a. After the first 6 patients were treated per the initial protocol, the frequency of IFN-a administration was decreased to Days 1-3 on weeks 1, 3, and 5 of the 7-week cycle for 5 additional patients. Lethargy, fever, chills, myalgias, alopecia, and anorexia occurred in all patients. Other toxicities included nausea and vomiting (91%), central-nervous-system depression or mood changes (64%), headaches (55%), and elevation of liver enzymes (36%). Grade 3-4 leukopenia occurred in 4 (45%) of 11 patients, and Grade 3-4 thrombocytopenia in 3 (27%) of 11 patients. Due to myelosuppressive effects, BCNU dose was not escalated. Median survival of the cohort was 44 months. Objective responses occurred in 5 (56%) of 9 patients and median duration of response was 33 months. The MTD of this combination after radiation therapy is IFN-a 12 x 10(6) units/m2 Days 1-3, on Weeks 1, 3, and 5 of a 7-week cycle and BCNU 150 mg/m2 Day 1, every 7 weeks., Conclusions: Treatment with radiation, IFN-a, and BCNU is feasible and effective in patients with high-grade gliomas, although constitutional symptoms from IFN-a are substantial.

Purpose: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults., Patients and Methods: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently., Results: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients., Conclusion: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

Purpose: To evaluate survival and patterns of recurrence in patients with primary central nervous system germinoma treated with radiation therapy., Methods and Materials: Data regarding 48 patients with histologically confirmed, primary central nervous system germinoma were reviewed. All had been operated on at the Mayo Clinic between the years 1935 and 1993. Thirty-two patients (67%) were treated since 1973. The study group included 39 males and 9 females, with a median age at diagnosis of 17 years (range, 6-42 years). Twelve patients (25%) were treated with craniospinal axis irradiation, 11 (23%) received whole-brain irradiation without spinal axis irradiation, and 24 (50%) underwent partial-brain irradiation. Treatment volumes were unknown in one patient. The median dose to the primary tumor was 44.00 Gy (range, 7.44-59.40 Gy). The median follow-up was 5.5 years (range, 4 months to 37 years)., Results: Actuarial 5-year and 10-year survival for the entire study group of patients was 80%. There was a trend toward improved survival in patients treated after 1973 (introduction of computed tomography) with 5-year and 10-year survival of 91% vs. 63% in prior years (p = 0.07). For the group of 31 patients treated since 1973 with known treatment volumes, the spinal axis failure rate at 5 years was 49% for patients treated with partial brain fields (11 patients) vs. 0% for those having undergone whole brain (10 patients) or craniospinal axis (10 patients) irradiation (p = 0.007). The rate of brain failure was also significantly higher in patients receiving less than whole-brain irradiation; at 5 years, 45% of the patients treated with partial-brain fields had intracranial recurrence of disease compared to 6 % of patients treated with craniospinal axis or whole-brain irradiation (p = 0.01). Among the 32 modern era patients, the rate of brain failure was higher in patients who received doses less than 40 Gy (median dose, 48.55 Gy; range, 30.60-59.40 Gy) to the primary tumor (5-year brain failure rate 52% vs. 11%, p = 0.002)., Conclusion: The long-term survival of patients with histologically proven CNS germinoma treated with radiation is excellent. Whole-brain or craniospinal axis irradiation appears to result in fewer spine and brain failures than does partial-brain irradiation. Furthermore, the administration of doses greater than 40 Gy to the primary tumor is associated with better local control.

Purpose: This analysis was performed to determine the clinical outcome of patients with primary nongerminomatous germ cell tumors of the brain. The efficacy of various treatment options was evaluated., Methods and Materials: A total of 57 patients with primary nongerminomatous germ cell tumors of the brain were identified. Patient-related data were collected and analyzed retrospectively. Follow-up in surviving patients ranged from 3 to 243 months (median follow-up 36). Survival and failure rates were determined using the Kaplan-Meier method, and differences between the survival curves were evaluated using either the log rank test or the Wilcoxon test., Results: The 3-year survival rate was 86% for patients with mature teratomas, 67% for patients with immature teratomas, 44% for patients with mixed germ cell tumors, and 13% for patients with the other histologic types (p = 0.02). The 3-year survival rate was 0% for patients having biopsies alone, 32% for patients having subtotal resections, and 73% for patients having gross total resections (p = 0.0001). Patients with tumors other than mature or immature teratomas were evaluated for possible relationships between the administration of chemotherapy or radiotherapy and survival. Patients who received chemotherapy had a 3-year survival rate of 56% compared to 8% for those patients who did not receive chemotherapy (p = 0.0001) Patients who received radiotherapy had a 3-year survival rate of 46% compared to 11% for those patients who did not receive radiotherapy (p = 0.0015)., Conclusion: The survival of patients with primary nongerminomatous germ cell tumors of the brain is dependent on tumor histology and the extent of surgical resection. Patients with tumors other than mature or immature teratomas appear to benefit from the administration of chemotherapy and radiotherapy.

Background: Brain metastases occur in 25% to 35% of all cancer patients, with colorectal carcinoma accounting for approximately 8% of these. Information about patients with brain metastases from colorectal carcinoma is limited, with the largest previous series reporting only 40 patients. To date there have been no reports describing the subgroup of patients with long term survival ( > 1 yr)., Methods: A retrospective review of 150 patients seen at the Mayo Clinic between 1976 and 1993 with pathologic (56) and/or radiographic (94) confirmation of brain metastases from colorectal carcinoma is presented., Results: The majority of patients (82%) with brain metastases from colorectal carcinoma have concomitant extracerebral metastases, especially in the lungs. Only 16% of the patients survived > 1 year after diagnosis (4 > 4 yrs., 2 > 10 yrs). Of these, 92% had single cerebral metastases and 38% had no systemic metastases. In addition, young age and the absence of bony metastases or memory loss were associated with increased survival. Median survival for all of the patients receiving surgery and radiotherapy (39), surgery alone (11), radiotherapy alone (79) and supportive care (17) are 42, 45, 16, and 8 weeks, respectively. Thirty percent of the patients treated with radiotherapy showed regression of their tumors on follow-up head scans; three had complete regression., Conclusions: One-year survivors of brain metastases from colorectal carcinoma were uncommon, accounting for 16% of the patients and most of these (92%) had solitary lesions. Nineteen of 24 long term survivors had surgical resection as part of their treatment. Given the similar results in patients treated with surgery plus radiotherapy and those treated with surgery alone, as well as the potential long term side effects of radiotherapy, withholding radiotherapy for those patients with the possibility of long term survival should be considered.

Background: Pineal parenchymal tumors are rare; therefore, only limited clinical data regarding their behavior is available. This study was performed to provide further information regarding the pathologic features, clinical behavior, and response to therapy of these tumors., Methods: This study includes data concerning 30 patients (15 male and 15 female patients) with pineal parenchymal tumors (PPT) diagnosed between 1939 and 1991. Based on gross and microscopic features, tumors were divided into four groups: pineocytomas (9); PPT with intermediate differentiation (4); mixed PPT exhibiting elements of both pineocytoma and pineoblastoma (2); and pineoblastomas (15). At the time of diagnosis, four patients had evidence of spinal seeding (two with pineoblastoma, two with PPT with intermediate differentiation). Twenty-two patients received radiation therapy (RT): 6 were treated to local fields, 7 to the whole brain, and 9 to the craniospinal axis., Results: For patients who received RT and had a minimum follow-up of 6 months, local failure occurred in one of four patients with pineocytomas, zero of four patients with PPT with intermediate differentiation, one of two with mixed PPT, and four of nine (44%) with pineoblastomas. In patients receiving > or = 50 Gy to the primary tumor, 0 of 12 had local failure compared with 6 of 7 (86%) patients receiving lesser doses. Leptomeningeal failure occurred in zero of four patients with pineocytomas, zero of four patients with PPT with intermediate differentiation, one of two with mixed PPT, and four of nine with pineoblastomas. All leptomeningeal failures occurred in patients with persistent primary tumor. Of the patients with seeding tumors (PPT other than pineocytomas) one of seven (14%) developed leptomeningeal failure when treated with craniospinal irradiation, compared with four of eight (50%) treated to lesser volumes. The projected 1-year, 3-year, and 5-year survival rates of patients with pineocytomas were 100%, 100%, and 67%, and were 88%, 78%, and 58% for those with the other forms of PPT, respectively., Conclusions: RT recommendations are described in detail and include the use of doses of > or = 50 Gy to areas of gross disease and the administration of craniospinal irradiation in patients with tumors prone to seeding. Surgical, chemotherapeutic, and pathologic considerations are discussed.

Twenty-seven hemangioblastomas of the central nervous system were treated at the Mayo Clinic with radiation therapy from January 1963 to August 1983. Six patients had von-Hippel Lindau syndrome, and four presented with polycythemia. The median age among the 15 males and 12 females was 48 years (range 20-68). Two clinical groups were apparent: those that received postoperative radiation therapy for clinically suspect, or microscopically positive margins (6 patients) and those who underwent therapy for gross residual disease (20 patients). One patient did not fall into either group because his initially unresectable tumor was treated with planned pre-operative radiotherapy to 40 Gy and was subsequently successfully cured by surgery. Because the combined modality approach did not allow assessment of local control with radiation alone, he was excluded from the gross residual cohort in terms of time-dose relationship analysis. The cohort with gross residual disease was particularly unfavorable as 12 of these patients had developed 17 local recurrences prior to radiation. Three had multiple lesions, and four had the von-Hippel Lindau syndrome. In-field disease control appeared to be improved when patients were treated more aggressively. Patients treated to a dose of 50 Gy manifested local control in 4/7 (57%) vs 4/12 (33%) in patients treated to less than 50 Gy. In-field local control was also better if patients received a TDF greater than 75 (local control in 66%) vs a TDF of 65-75 (local control in 22%). Actuarial analysis of in-field disease control showed more aggressive treatment improved control whether analyzed by dose level (greater than or equal to 50 Gy vs less than 50 Gy, or TDF greater than 75 vs less than 75). Four of the six patients who received radiation therapy for microscopically positive or clinically suspect margins achieved local control. Both patients manifesting in-field relapse were successfully surgically salvaged. Overall survival for the entire group of 27 patients was 85%, 58%, 58%, and 46% at 5, 10, 15, and 20 years, respectively. Recurrence-free survival was 76%, 52%, and 42% at 5, 10, and 15 years, respectively. Half of all in-field recurrences had occurred by 2 years, but the remaining half recurred from 5.6 to 14.4 years. Patients who developed in-field failure usually died from disease with a median survival of only 1.5 years, but surgical salvage was accomplished in 4/12. Hydro-myelia developed in two patients and required operation. Surveillance for systemic tumors also was important and revealed seven benign and four malignant tumors.(ABSTRACT TRUNCATED AT 400 WORDS)