Faculty Bibliography

Many physicians rely upon neuroimaging studies alone to select therapy for adult patients suspected of having a glial neoplasm, in the belief that certain imaging features accurately characterize the histological diagnosis of low-grade astrocytoma. During a 4-year interval when both computerized tomography and magnetic resonance imaging was available, the authors performed stereotactic biopsies on 20 consecutive adult patients who were suspected of having an astrocytoma. The patients were generally young (mean age 37 years), had seizures (17 cases), and had lobar lesions. An accurate histological diagnosis was obtained, without morbidity, in all 20 patients. Only 10 (50%) in fact had low-grade astrocytomas, whereas nine (45%) had anaplastic astrocytomas and one (5%) had encephalitis. The results of this study indicate that modern high-resolution neuroimaging alone cannot be used as a reliable tool to predict the histological diagnosis of astrocytoma (50% false-positive rate). All patients with supratentorial mass lesions that exhibit the "typical" imaging features of astrocytoma should undergo stereotactic biopsy for confirmation in order that appropriate management may be planned.

Microsurgical resection is the primary management approach for patients with intracranial schwannomas. Recent studies have demonstrated that stereotactic radiosurgery is an effective therapeutic modality for patients with acoustic schwannomas. To define the role of radiosurgery in the management of patients with nonacoustic schwannomas, we reviewed the results of gamma unit stereotactic radiosurgery in six patients with trigeminal and five patients with jugular foramen region schwannomas. No patient with a trigeminal schwannoma demonstrated tumor growth during a mean follow-up of 21 months (range, 7-35 mo), whereas one patient with a jugular foramen region schwannoma had an increase in tumor size 7 months after radiosurgery. No new cranial nerve or brain stem deficits were noted in either patient group after radiosurgery. In this early experience, radiosurgery proved an effective primary or adjuvant technique for selected patients with schwannomas of the trigeminal, glossopharyngeal, or vagus nerves. Using our described method, the safety of radiosurgery was demonstrated on the brain stem, regional cranial nerves, and especially those cranial nerves intimately associated with the tumor.

PURPOSE: The error frequency in setting stereotactic coordinates for gamma knife radiosurgery was investigated to determine what quality assurance safeguards are necessary. METHODS AND MATERIALS: A prospective study of 200 consecutive isocenter settings for gamma knife radiosurgery was analyzed to identify the frequency of spontaneous errors in setting and checking stereotactic coordinates (corrected prior to treatment). An additional 25 coordinate errors were introduced at random among the next 200 consecutive isocenter settings to provide additional data on identification of errors. RESULTS: Stereotactic coordinates required resetting in 12% (24/200) of the isocenters treated due to errors of 0.25-0.50 mm (8%) and 1-20 mm (4%). This comprised 2.2% (26/1200) of the individual coordinate settings. The frequency of these errors was significantly related to the specific directional coordinate set (p = 0.0004) and experience (p = 0.016). Errors were identified by 83.5% (91/109) of the observers checking the settings (60.0% of 0.25 mm errors, 94.6% of errors > or = 0.5 mm, p = 0.0000). Verification of stereotactic coordinates by two observers reduces the probability of an undetected error > or = 0.25 mm to 1/1,392 and to 1/154,712 for errors > or = 1 mm. CONCLUSION: Errors in setting stereotactic coordinates are common (12% prior to checking) but are corrected with a high degree of confidence by a quality assurance policy requiring coordinate verification by a minimum of two observers.

Stereotactic radiosurgery using the gamma unit has been used to manage patients with brain stem tumors or vascular malformations as an alternative to microsurgical resection. Whether associated with the pial or ependymal brain stem surface or within the brain stem parenchyma proper, radiosurgery provides relatively safe and effective management. Radiosurgery is a valuable alternative for many patients with pathologic lesions of the brain stem and may represent the only surgical option for some patients.

To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to evaluate the results of radiosurgery for acoustic tumors and to identify optimum treatment parameters, an analysis of tumor control, as well as incidences of hearing loss, facial and trigeminal neuropathies was undertaken. Between August 1987 and August 1991, 134 patients with 136 acoustic tumors received stereotactic gamma knife radiosurgery at the University of Pittsburgh. Median follow-up was 24 months (range: 6-56 months). Tumor volumes ranged from 0.10 to 17.00 cm3 (median = 2.75 cm3). From one to ten isocenters were utilized per tumor treated (median = 3). Minimum tumor doses varied from 12 to 20 Gy (median = 17 Gy). The 4-year actuarial tumor control rate was 89.2 +/- 6.0%. Some degree of hearing (by pure tone audiometry) was preserved in 71.0 +/- 4.4% of patients. The actuarial rates for preservation of either pretreatment hearing level or useful hearing were 34.4 +/- 6.6% and 35.1 +/- 97% respectively. Respectively, the actuarial incidences of postradiosurgery facial and trigeminal neuropathies were 29.0 +/- 4.4% and 32.9 +/- 4.5%, respectively. No significant factors affecting tumor control were identified. Multivariate analysis identified a significantly increased risk of hearing loss in patients with neurofibromatosis (p = 0.0003) as well as decreased risks of facial and trigeminal neuropathies with both decreasing tumor diameter (p = 0.001) and increasing number of isocenters treated (p = 0.003). Radiosurgery is a safe and effective treatment for acoustic neuromas with acceptable morbidity that may be lowered by the use of multiple isocenter treatment techniques and by earlier treatment of small tumors.

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

The challenges associated with microsurgery of vascular malformations located in the midbrain, pons and medulla have promoted the development of alternative therapeutic techniques. To assess the efficacy and safety of radiosurgery in the management of brain stem vascular malformations we reviewed our 5-year experience in 50 patients evaluated between 4 and 51 months (mean, 25 months) after radiosurgery. Twenty-eight patients (56%) underwent gamma unit radiosurgery for symptomatic arteriovenous malformations (AVMs), and 22 patients (44%) for angiographically occult vascular malformations (AOVMs). Patients varied in age from 7 to 76 years (mean, 39 years). Forty-one patients (82%) had from 1 to 5 hemorrhages prior to gamma knife radiosurgery. Ten (20%) had one or two prior unsuccessful operations, and 37 (74%) presented with a neurological deficit. Of the patients with AVMs, 6 were considered Spetzler Grade III, and 22 (79%) Grade VI (inoperable: major component within the brain stem parenchyma). Forty-four malformations (88%) were adjacent to or within the midbrain and pons; the remainder involved the medulla. Average malformation diameters varied from 6 to 30.4 m (mean, 20.6; mean volume 4614 mm3). The minimal radiation dose to the margin of the malformations ranged from 12 to 25.6 Gy (mean, 18.9 Gy). Of the 28 patients with AVMs, 8 had follow-up angiograms at a minimum of 2-years after radiosurgery (or sooner if their MRIs suggested obliteration). Of these patients, 7 (88%) showed complete obliteration of their malformations. No patients with AOVMs rehemorrhaged if more than 15 months elapsed after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)