Faculty Bibliography

Surgeons perform stereotactic radiosurgery as the main alternative to acoustic tumor (vestibular schwannoma) resection. The goals of radiosurgery include preservation of neurological function and prevention of tumor growth. Longer-term outcomes are not well documented for patients with solitary tumors or those with neurofibromatosis Type 2 (NF2). To define outcomes, the authors evaluated 462 consecutive patients with solitary acoustic tumors and 40 patients with NF2 (total of 45 tumors treated) who underwent radiosurgery between 1987 and 1998. Serial imaging studies, clinical evaluations, and a patient survey were performed. The average tumor margin dose was 15 Gy, and the mean transverse tumor diameter was 22 mm. In patients with solitary tumors, prior resection had been performed in 111 patients (24%); 27 patients experienced tumor recurrence after a "total resection." The clinical tumor control rate (no resection required) was 98%. In non-NF2 patients followed for at least 5 years, 100 tumors (61.7%) were smaller, 53 (32.7%) remained unchanged in size, and nine (5.6%) were slightly larger. Resection was performed in four patients (2.4%). Neurological deficits after radiosurgery all occurred within the first 28 months. The rates of facial and trigeminal neuropathy varied with radiosurgery technique. In patients with NF2, 16 tumors were smaller, 28 remained unchanged, and one enlarged (overall 98% control rate at median 3-year follow up). Resection was performed in three patients (7%). Useful hearing was preserved in six (43%) of 14 NF2 patients who had useful hearing before radiosurgery. Radiosurgery provided long-term tumor control associated with high rates of neurological function preservation. No further tumor surgery was necessary in 98% of patients with solitary tumors followed for a minimum of 5 years.

BACKGROUND: Trigeminal neuralgia is a disabling pain syndrome responsive to both medical and surgical therapies. Stereotactic radiosurgery using the gamma knife can be used to inactivate a specified volume in the brain by cross firing 201 photon beams. We evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery. METHODS: All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients. RESULTS: After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity. CONCLUSIONS: Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted.

OBJECT: The indications, operative findings, and outcomes of vestibular schwannoma microsurgery are controversial when it is performed after stereotactic radiosurgery. To address these issues, the authors reviewed the experience at two academic medical centers. METHODS: During a 10-year interval, 452 patients with unilateral vestibular schwannomas underwent gamma knife radiosurgery. Thirteen patients (2.9%) underwent delayed microsurgery at a median of 27 months (range 7-72 months) after they had undergone radiosurgery. Six of the 13 patients had undergone one or more microsurgical procedures before they underwent radiosurgery. The indications for surgery were tumor enlargement with stable symptoms in five patients, tumor enlargement with new or increased symptoms in five patients, and increased symptoms without evidence of tumor growth in three patients. Gross-total resection was achieved in seven patients and near-gross-total resection in four patients. The surgery was described as more difficult than that typically performed for schwannoma in eight patients, no different in four patients, and easier in one patient. At the last follow-up evaluation, three patients had normal or near-normal facial function, three patients had moderate facial dysfunction, and seven had facial palsies. Three patients were incapable of caring for themselves, and one patient died of progression of a malignant triton tumor. CONCLUSIONS: Failed radiosurgery in cases of vestibular schwannoma was rare. No clear relationship was demonstrated between the use of radiosurgery and the subsequent ease or difficulty of delayed microsurgery. Because some patients have temporary enlargement of their tumor after radiosurgery, the need for surgical resection after radiosurgery should be reviewed with the neurosurgeon who performed the radiosurgery and should be delayed until sustained tumor growth is confirmed. A subtotal tumor resection should be considered for patients who require surgical resection of their tumor after vestibular schwannoma radiosurgery.

OBJECT: The purpose of this study was to analyze patient outcomes and to define the role of radiosurgery in patients who have undergone prior microsurgical resection of their vestibular schwannoma. METHODS: The authors evaluated the pre- and postoperative clinical and neuroimaging characteristics of 76 consecutive patients with 78 vestibular schwannomas who underwent radiosurgery after previous surgical resection. Twenty-nine patients (37% of tumors) had undergone more than one prior resection. Forty-three patients (55% of tumors) had significant impairment of facial nerve function (House-Brackmann Grades III-VI) after their microsurgical procedure; 50% had trigeminal sensory loss, and 96% had poor speech discrimination (< 50%). The median evaluation period following radiosurgery was 43 months (range 12-101 months). Tumor growth control after radiosurgery was achieved in 73 tumors (94%). Six patients underwent additional surgical resection despite radiosurgery (median of 32 months after radiosurgery), and one patient underwent repeated radiosurgery for tumor progression outside the irradiated volume. Eleven (23%) of 47 patients with Grades I to III facial function before radiosurgery developed increased facial weakness after radiosurgery. Eleven patients (14%) developed new trigeminal symptoms. CONCLUSIONS: Radiosurgery proved to be a safe and effective alternative to additional microsurgery in patients in whom the initial microsurgical removal failed. Stereotactic radiosurgery should be considered for all patients who have regrowth or progression of previously surgically treated vestibular schwannomas.

OBJECT: The authors studied outcomes in patients who had undergone radiotherapy for nonfunctional pituitary adenoma to assess long-term tumor control and to identify factors affecting tumor control such as higher radiation doses, improved imaging, and histological characteristics of the tumor. METHODS: In this retrospective study, the authors evaluated 120 patients who received radiotherapy for nonfunctional pituitary adenomas between 1960 and 1991. The median follow-up period was 9 years (range 1 month-32 years). Radiation doses varied between 37.6 and 65.6 Gy (median 46.7 Gy). Tumors progressed in 15 of the 120 patients by 1 to 25 years after radiotherapy. Actuarial tumor control rates at 10, 20, and 30 years were 87.5+/-3.6%, 77.6+/-6.3%, and 64.7+/-12.9%, respectively. Tumor progression after radiotherapy occurred significantly more often (p=0.0397) in patients with oncocytoma than in patients with nononcocytic null cell adenoma. No other factors correlated significantly with tumor control. One case of optic and oculomotor neuropathy developed 4.5 years after a maximum dose of 50 Gy in 25 fractions. Radiation-induced neoplasms (meningioma and glioblastoma multiforme) developed at a rate of 2.7% at 10 and 30 years. CONCLUSIONS: The oncocytic variant of null cell pituitary adenoma appears less sensitive to control by radiotherapy than nononcocytic undifferentiated cell adenoma. A follow-up period extending beyond 20 years is needed adequately to assess the efficacy of radiotherapy for tumor control. Doses of 40 or 45 Gy in 20 or 25 fractions, respectively, appear optimal.

BACKGROUND: Stereotactic radiosurgery is the principal alternative to microsurgical resection for acoustic neuromas (vestibular schwannomas). The goals of radiosurgery are the long-term prevention of tumor growth, maintenance of neurologic function, and prevention of new neurologic deficits. Although acceptable short-term outcomes have been reported, long-term outcomes have not been well documented. METHODS: We evaluated 162 consecutive patients who underwent radiosurgery for acoustic neuromas between 1987 and 1992 by means of serial imaging tests, clinical evaluations, and a survey between 5 and 10 years after the procedure. The average dose of radiation to the tumor margin was 16 Gy, and the mean transverse diameter of the tumor was 22 mm (range, 8 to 39). Resection had been performed previously in 42 patients (26 percent); in 13 patients the tumor represented a recurrence of disease after a previous total resection. Facial function was normal in 76 percent of the patients before radiosurgery, and 20 percent had useful hearing. RESULTS: The rate of tumor control (with no resection required) was 98 percent. One hundred tumors (62 percent) became smaller, 53 (33 percent) remained unchanged in size, and 9 (6 percent) became slightly larger. Resection was performed in four patients (2 percent) within four years after radiosurgery. Normal facial function was preserved in 79 percent of the patients after five years (House-Brackmann grade 1), and normal trigeminal function was preserved in 73 percent. Fifty-one percent of the patients had no change in hearing ability. No new neurologic deficits appeared more than 28 months after radiosurgery. An outcomes questionnaire was returned by 115 patients (77 percent of the 149 patients still living). Fifty-four of these patients (47 percent) were employed at the time of radiosurgery, and 37 (69 percent) remained so. Radiosurgery was believed to have been successful by all 30 patients who had undergone surgery previously and by 81 (95 percent) of the 85 who had not. Thirty-six of the 115 patients (31 percent) described at least one complication, which resolved in 56 percent of those cases. CONCLUSIONS: Radiosurgery can provide long-term control of acoustic neuromas while preserving neurologic function.

PURPOSE: The development of a brain metastasis represents an ominous event for patients with malignant melanoma. We evaluated results after stereotactic radiosurgery (SR) for patients with metastastic melanoma to identify patient outcomes and factors for survival. METHODS: The authors reviewed the management results of 60 consecutive patients with melanoma metastases, with a total of 118 melanoma brain metastases, undergoing SR during a 9-year interval. Of these, 51 also had whole-brain radiation therapy (WBRT). A total of 118 tumors of mean volume of 2.95 ml (range, 0.1-25.5 ml) were treated by SR with a mean margin dose of 16.4 Gy (range, 10 to 20 Gy). Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival in 60 patients. RESULTS: Median survival was 7 months after SR in all 60 patients and 10 months from brain tumor diagnosis (mean follow-up period, 9.3 months). Lack of active systemic disease and a solitary metastasis were associated with improved survival in multivariate analysis (median, 15 months). The imaging-defined local control rate of evaluable tumors (n = 72) was 90% (disappearance = 11%, shrinkage = 44%, and stable = 35%). Local recurrence developed in 7 patients and remote brain disease developed in 14 patients. WBRT combined with radiosurgery did not improve survival nor local tumor control. New brain metastases developed less often when WBRT was added to SR (23% vs. 44%), but this difference was not significant. Only 4 patients (7%) died from progression of a radiosurgery-managed tumor. No patient developed a delayed radiation-related complication, but 3 patients developed delayed intratumoral hemorrhage at the radiosurgery site, 2 of whom had new symptoms. CONCLUSIONS: Stereotactic radiosurgery for melanoma brain metastasis is effective and is associated with few complications. The use of radiosurgery alone is an appropriate management strategy for many patients with solitary tumors.

To evaluate the role of Gamma Knife radiosurgery as the first surgical therapy in the management of medically refractory trigeminal neuralgia, we reviewed outcomes on our first 23 patients who had radiosurgery as primary surgical therapy. These patients represented 19% of our overall series. Mean patient age was 66 years, and mean follow-up after radiosurgery was 12 months (range 5-33 months). For most patients, radiosurgery was performed because the patient had medical contraindications to open surgery. 14 patients had 70-Gy radiosurgery, and 9 patients, 80 Gy. Radiosurgery was performed using a single 4 mm isocenter. Postoperative imaging 6 to 9 months following radiosurgery confirmed regions of enhancement at the radiosurgical target. Nine patients received 70 Gy, and 8 patients had 80 Gy. 17 patients (74%) had an excellent result (total pain relief). Five patients (22%) achieved a good result (50-90% improvement). One patient had a poor result (4%) after 70-Gy radiosurgery and subsequently underwent microvascular decompression. No patient developed facial numbness or any other complication after Gamma Knife radiosurgery. Gamma Knife radiosurgery using 70 or 80 Gy targeted to the proximal trigeminal nerve proved to be a safe and effective primary surgical therapy for medically refractory trigeminal neuralgia. The overall response rate (96%) was similar to that obtained with other surgical therapies performed as a first procedure.

PURPOSE: To evaluate the imaging and pathological correlates of successful or risk-related stereotactic radiosurgery (SR). Methods and Materials. The ten-year Gamma Knife experience in 2,344 patients at the University of Pittsburgh was reviewed. In addition, the results or radiosurgery primate, rat, and mouse models were analyzed. Successful results and untoward complications were evaluated. RESULTS: Dose, volume, location and histology affected the imaging changes seen after SR. Imaging changes range from central loss of contrast ('black holes'), shrinkage with diffuse contrast uptake ('white dwarfs'), or stabilization or growth arrest. Limited pathological data indicates that the prevention of cell division coupled with vascular obliteration results in tumor control, whereas a progressive endothelial proliferative and obliterative response results in arteriovenous malformation (AVM) obliteration. Perilesional imaging changes, especially in vascular malformations, may reflect flow phenomena, interstitial edema, or profound reactive astrocytosis ('supernovas'). CONCLUSION: Imaging changes correlate with both success and risks of stereotactic radiosurgery; however, pathological correlates are limited. High resolution neurodiagnostic imaging provides the best quality control available to assess the response to stereotactic radiosurgery. In the future, additional molecular probes are necessary to assess the radiobiological effects of radiosurgery.

BACKGROUND: Parasagittal meningiomas, especially when associated with the middle or posterior third of the superior sagittal sinus, pose difficult management challenges. Initial surgical excision is associated with high morbidity and frequent tumor recurrence after subtotal resection. Neurological deficits are cumulative when multiple resections are required. No consistent management approach exists for patients with such tumors. In addition to observation, management options include resection, stereotactic radiosurgery, or fractionated radiation therapy used alone or in combination. METHODS: Sixteen centers where resection, gamma knife radiosurgery, and/or radiation therapy were available provided management data on 203 patients with histologically benign meningiomas from the time of initial diagnosis through follow-up after radiosurgery. The timing of resections, parameters of radiosurgery, rates of tumor control, morbidity, and functional patient outcomes were studied. The median follow-up duration in this study was 3.5 years (maximum, 33 yr after presentation and 6 yr after radiosurgery). RESULTS: The tumors were located in the anterior superior sagittal sinus in 52 patients, at the middle of the sinus in 91, and at the posterior portion of the sinus in 60. The mean tumor volume at the time of radiosurgery was 10 cc. In patients who underwent radiosurgery as the primary therapy (n = 66), the 5-year actuarial tumor control rate was 93 +/- 4%. No clinical failure (need for additional therapy or worsened neurological function) occurred in patients who had smaller tumors (<7.5 cc) and who had never undergone resection (n = 41). The 5-year control rate for patients with previous surgery was only 60 +/- 10%; the control rate for the radiosurgery-treated volume was 85%. Most failures resulted from remote tumor growth. Multivariate analyses identified significantly decreased tumor control with increasing tumor volume (P = 0.002) and previous neurological deficits (P = 0.002). The rate of transient, symptomatic edema after radiosurgery was 16%, was more common with larger tumors, and occurred within 2 years. Of 33 patients who were employed at the time of radiosurgery for whom a minimum of 1 year of follow-up data were available, 30 remained employed (91%). A decrease in functional status after radiosurgery was noted in only 3 of 33 (9%) employed and 7 of 77 (9%) unemployed patients. CONCLUSION: In patients with smaller tumors (<3 cm in diameter) and patent sagittal sinuses, we advocate radiosurgery alone as the first surgical procedure. Patients with larger tumors and those with progressive neurological deficits resulting from brain compression should first undergo resection. Planned second-stage radiosurgery should be performed soon afterward for any residual tumor nodule or neoplastic dural remnant. Multimodality management may enhance long-term tumor control, reduce the need for multiple resections, and maintain the functional status of the patient.