Faculty Bibliography

The indications for stereotactic radiosurgery for patients with cavernous malformations of the brain are discussed. Specific reference is made to technique and dose selection and to the results and potential complications of this approach. Radiosurgery is an alternative to microsurgical resection for some patients with malformations in high-risk brain locations.

OBJECTIVE: To determine the risks and survival benefit associated with implantation of an absorbable, 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer, we prospectively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group. METHODS: Over a 29-month period, 62 patients underwent operations. All had tumor growth despite standard treatment, a Karnofsky performance score of > or =70, and histopathological confirmation of glioblastoma. Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers (wafer group) at a median 44 weeks from diagnosis (6 women, 11 men; median age, 56 years). A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period, but not receiving wafers, was identified. Surgery was performed at a median 47 weeks from diagnosis (14 women, 31 men; median age, 54 years). RESULTS: Within 6 weeks of surgery, 13 complications were identified in 8 patients in the wafer group. In the cohort group, 6 patients sustained 8 complications. We were unable to identify any survival advantage using Kaplan-Meier analysis. In the wafer group, median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation. In the cohort group, median survival was 97 weeks from diagnosis and 50 weeks from operation. CONCLUSION: 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications, particularly those related to infection and wound healing. No clear survival benefit associated with wafer implantation was identified.

OBJECTIVE: Schwannomas that arise from the trigeminal nerve are rare and are usually managed by surgical resection. The role of radiosurgery in the care of patients with these basal tumors remains to be defined. METHODS: We reviewed the clinical presentation, management, and outcomes for 16 trigeminal schwannoma patients who underwent gamma knife stereotactic radiosurgery. Fifteen of the 16 patients presented with trigeminal sensory dysfunction. Nine patients had tumors in the region of the ganglion, six in the region of the trigeminal nerve root, and one in the region of the mandibular branch. Six patients had undergone one or more previous resections before radiosurgery. Ten underwent radiosurgery as the first procedure. The mean tumor volume was 5.3 cc (range, 1-17.8 cc). The mean tumor margin dose was 15.3 Gy (range, 12-20 Gy). RESULTS: During the average imaging follow-up of 44 months (range, 8-116 mo), the tumor control rate was 100% (regression in nine patients and no further tumor growth in seven patients). Five patients had improvement of clinical symptoms, and 11 remained unchanged. No new cranial nerve deficit developed in any patient. CONCLUSION: As a minimally invasive alternative to microsurgery, gamma knife radiosurgery proved to be an alternative primary or adjuvant strategy that controlled tumor growth, did not cause new deficits, and often improved presenting symptoms.

OBJECT: Stereotactic radiosurgery is a primary or adjuvant management approach used to treat patients with intracranial meningiomas. The goal of radiosurgery is long-term prevention of tumor growth, maintenance of the patient's neurological function, and prevention of new neurological deficits. The object of this study is to report longer-term patient outcomes. METHODS: The authors evaluated 99 consecutive patients who underwent radiosurgery for meningioma between 1987 and 1992. Evaluation was performed using serial imaging tests, clinical evaluations, and a patient survey that was administered between 5 and 10 years after radiosurgery. Four patients underwent two radiosurgery procedures for separate meningiomas. The average tumor margin dose was 16 Gy and the median tumor volume was 4.7 ml (range 0.24-24 ml). Fifty-seven patients (57%) had undergone prior resection, of which 12 procedures were considered "total." Five patients received fractionated radiation therapy before radiosurgery. Eighty-nine patients (89%) had skull base tumors. The clinical tumor control rate (no resection required) was 93%. Sixty-one (63%) of 97 tumors became smaller, 31 (32%) remained unchanged in size, and five (5%) were enlarged. Resection was performed in seven patients (7%), six of whom had undergone prior resection. New neurological deficits developed in five patients (5%) 3 to 31 months after radiosurgery. Twenty-seven (42%) of 65 responding patients were employed at the time of radiosurgery and 20 (74%) of these remained so. Radiosurgery was believed to have been "successful" by 67 of 70 patients who completed an outcomes questionnaire 5 to 10 years later. At least one complication was described by nine patients (14%) and in four patients the complications resolved. CONCLUSIONS: Five to 10 years after radiosurgery, 96% of surveyed patients believed that radiosurgery provided a satisfactory outcome for their meningioma. Overall, 93% of patients required no other tumor surgery. Incidences of morbidity in this early experience were usually transitory and relatively mild. Radiosurgery provided long-term tumor control associated with high rates of neurological function preservation and patient satisfaction.

PURPOSE: To characterize the magnetic resonance (MR) imaging response of brain metastases after gamma knife stereotactic radiosurgery and determine whether imaging features and tumor response rates correlate with local tumor control and survival. MATERIALS AND METHODS: Serial MR examinations were performed in 48 patients (25 men, 23 women; mean age, 58 years) with 78 lesions. Pretreatment and follow-up enhancing lesion volumes and imaging features were assessed. Rates of response to stereotactic radiosurgery were calculated. Prognostic imaging features affecting local control and survival were analyzed. RESULTS: Local tumor control was achieved in 66 (90%) of 73 metastases at 20 weeks after stereotactic radiosurgery; 61% maintained local control at 2 years. A homogeneous baseline enhancement pattern and initial good response rate (> 50% lesion volume reduction) predicted local control. Five metastases demonstrated a transient volume increase after treatment. The median survival time after stereotactic radiosurgery was 53 weeks and correlated with systemic disease burden and primary tumor type. CONCLUSION: Baseline homogeneous tumor enhancement and initial good response correlate with local control. Initial lesion growth does not preclude local control and may represent radiation-related change. Recognition of these serial MR imaging findings may guide image interpretation and influence treatment in patients with stereotactic radiosurgery-treated metastases.

OBJECT: Stereotactically guided radiosurgery is one of the primary treatment modalities for patients with acoustic neuromas (vestibular schwannomas). The goal of radiosurgery is to arrest tumor growth while preserving neurological function. Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2) represent a special challenge because of the risk of complete deafness. To define better the tumor control rate and long-term functional outcome, the authors reviewed their 10-year experience in treating these lesions. METHODS: Forty patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35 of them for solitary tumors. The other five underwent staged procedures for bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors) had undergone a median of two prior resections. The mean tumor volume at radiosurgery was 4.8 ml, and the mean tumor margin dose was 15 Gy (range 12-20 Gy). The overall tumor control rate was 98%. During the median follow-up period of 36 months, 16 tumors (36%) regressed, 28 (62%) remained unchanged, and one (2%) grew. In the 10 patients for whom more than 5 years of clinical and neuroimaging follow-up results were available (median 92 months), five tumors were smaller and five remained unchanged. Surgical resection was performed in three patients (7%) after radiosurgery; only one showed radiographic evidence of progression. Useful hearing (Gardner-Robertson Class I or II) was preserved in six (43%) of 14 patients, and this rate improved to 67% after modifications made in 1992. Normal facial nerve function (House-Brackmann Grade 1) was preserved in 25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34 (94%) of 36 patients. CONCLUSIONS: Stereotactically guided radiosurgery is a safe and effective treatment for patients with acoustic tumors in the setting of NF2. The rate of hearing preservation may be better with radiosurgery than with other available techniques.

PURPOSE: To evaluate the radioprotectant effects of the 21-aminosteroid U-74389G on the rat C6 glioma model after stereotactic radiosurgery. Because radiosurgery causes both tumor cytotoxicity, as well as regional brain edema, we hypothesized that this drug might exhibit advantageous or deleterious effects on healthy and neoplastic tissue. METHODS: Rats were implanted with 10(6) C6 glioma cells into the right frontal brain and randomized to a Control Group (n = 18), radiosurgery on Day 14 (50% isodose = 35 Gy) (n = 15), or radiosurgery preceded by a single 15 mg/kg intravenous dose of 21-aminosteroid (n = 27). All animals were killed by 90 days and evaluated for survival, tumor size, the presence or absence of regional parenchymal edema, or radiation-induced vasculopathy. RESULTS: After tumor implantation, median survival in the Control Group was 23 days. Significant improvements in median survival were noted after RS alone (median, 31 days; p = 0.02), and RS plus 21-aminosteroid (median, 59 days; p < 0.0001). In the Control Group, mean tumor diameter was 5.4 mm. After RS alone, the mean diameter was 3.2 mm (p = 0.002), and after RS plus 21-aminosteroid, 2.9 mm (p = 0.0002). In the Control Group, the tumor grew as a hypercellular, compact mass. Only 3 of 18 animals had peritumoral edema. In contrast, 7 of 15 animals in the RS group had evidence of edema (p = 0.006), but rats that received 21-aminosteroid showed no increase compared to controls (p = 0.38). Similarly, 6 of 15 animals that had radiosurgery alone showed evidence of vasculopathy (p = 0.005) compared to no animals in the control group and only 2 of 27 aminosteroid-treated animals. CONCLUSIONS: The 21-aminosteroid U-74389G exhibits a radioprotectant effect on normal brain tissue, but does not appear to protect the tumor in an in vivo rat radiosurgery model. We believe that the observed beneficial effects on healthy brain led to significant prolongation of animal survival; perhaps, by limiting the adverse effects of high-dose radiosurgery. This radioprotectant should now be evaluated in randomized clinical trials in patients with malignant brain tumors.

PURPOSE: To better understand radiation complications of arteriovenous malformation (AVM) radiosurgery and factors affecting their resolution. METHODS AND MATERIALS: AVM patients (102/1255) who developed neurological sequelae after radiosurgery were studied. The median AVM marginal dose (Dmin) was 19 Gy (range: 10-35). The median volume was 5.7 cc (range: 0.26-143). Median follow-up was 34 months (range: 9-140). RESULTS: Complications consisted of 80/102 patients with evidence of radiation injury to the brain parenchyma (7 also with cranial nerve deficits, 12 also with seizures, 5 with cyst formation), 12/102 patients with isolated cranial neuropathies, and 10/102 patients with only new or worsened seizures. Severity was classified as minimal in 39 patients, mild in 40, disabling in 21, and fatal in 2 patients. Symptoms resolved completely in 42 patients for an actuarial resolution rate of 54% +/- 7% at 3 years post-onset. Multivariate analysis identified significantly greater symptom resolution in patients with no prior history of hemorrhage (p = 0.01, 66% vs. 41%), and in patients with symptoms of minimal severity: headache or seizure as the only sequelae of radiosurgery (p < 0.0001, 88% vs. 34%). CONCLUSION: Late sequelae of radiosurgery manifest in varied ways. Further long-term studies of these problems are needed that take into account symptom severity and prior hemorrhage history.

The indications for and results after meningioma radiosurgery results are discussed. Particular emphasis is placed on longer-term results, the evolution of technique, complications, and recommendations regarding the role of radiosurgery together with other management strategies.

Advances in noninvasive diagnostic techniques have enabled physicians to diagnose acoustic tumors early, while hearing is still present. Applications of advanced operative techniques have allowed surgeons to decrease progressively the operative mortality to virtually zero, to save facial nerve function in a large number of patients, and even to preserve serviceable hearing in selected patients. Documented improvement in hearing after acoustic tumor surgery is rare. During the last decade, stereotactic radiosurgery has evolved as a noninvasive surgical option for acoustic tumors. Hearing improvement after radiosurgery has not been reported. The authors observed hearing improvement in 21 out of 487 patients who had radiosurgery during a 10-year interval. This article reviews their experience of hearing improvement after radiosurgery and suggests possible reasons that hearing can not only be retained but also improved in selected patients.