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17 early in series 12-14 recently

11-18 (median 13)

94% for unilateral 84% for NF2

36 mo

52 mo

93% (7% enlarged, but only 2% required surgery)

94% (6% enlarged, but only 2% required surgery)

91% (5-yr actuarial)

97% (freedom from resection)

94% for primary radiosurgery 89% for previously operated

29% prior to 1994 5% since 1994

(5 yr actuarial) (7% improved)

29% prior to 1994 2% since 1994

Fig. 9. (A) Contrast-enhanced MR image shows a 3-cm right vestibular schwannoma. (B) Enhanced MR image shows the same tumor, 2 yr later. Typically, tumors shrink slowly after radiosurgery. Although the MRI never normalizes, more than 90% of tumors so treated never grow again.

neuropathy and radiographic tumor control (Fig. 9), were obtained from a prospectively maintained, computerized database.

The authors performed statistical analyses to compare the incidence of post-treatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow-up for this group was 36 mo (range 18-94 mo). The tumor control analysis included 133 patients. The median duration of radiological follow-up in this group was 34 mo (range 6-94 mo). The overall 2-yr actuarial incidences of facial and trigeminal neuropathies were 11.8 and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively. An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-yr actuarial tumor control rate was 87% (95% confidence interval 76-98%). Based on this study, the authors currently recommend a peripheral dose of 12.5Gy for almost all acoustics, as the dose most likely to yield long-term tumor control without causing cranial neuropathy.

Spiegelmann et al. (95,96) recently reported their experience. They reviewed the methods and results of LINAC radiosurgery in 44 patients with acoustic neuromas who were treated between 1993 and 1997. CT scanning was selected as the stereotactic imaging modality for target definition. A single, conformally shaped isocenter was used in the treatment of 40 patients; two or three isocenters were used in four patients who harbored very irregular tumors. The radiation dose directed to the tumor border was the only parameter that changed during the study period: in the first 24 patients who were treated the dose was 15-20 Gy, whereas in the last 20 patients the dose was reduced to 11-14 Gy. After a mean follow-up period of 32 mo (range 12-60 mo), 98% of the tumors were controlled. The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients and persisted to a mild degree in 8%. Radiation dose correlated significantly with the incidence of cranial neuropathy, particularly in large tumors (> 4 cm3).

Several reports on smaller series of patients treated with linear accelerator-based radiosurgery for VS have been published in recent years. Martens et al. (97) reported on 14 patients with at least 1 yr of follow-up after radiosurgery in the LiNAC unit in the University Hospital in Ghent, Belgium. A mean marginal dose of 19.4 Gy (range 16-20 Gy) was delivered to the 70% isodose line with a single isocenter. Mean follow-up duration was 19 mo (range 12-24 mo). During this relatively short follow-up interval, 100% radiographic tumor control has been achieved (29% regressed, 71% stable, zero enlarged). Rates of delayed facial and trigeminal neuropathy were 21 and 14%, respectively, and two of three facial nerve deficits resolved. Preoperative hearing was preserved 50% of the time.

Valentino and Raimondi (98) reported on 23 patients treated with LINAC radiosurgery in Rome. Five of these had neurofibromatosis, and seven (30%) had undergone previous surgery. Total radiation dose to the tumor margin ranged from 12 to 45 Gy (median 30 Gy) and was delivered in one to five sessions. One or two isocenters were used, and mean duration of follow-up was 40 mo (range 24-46 mo). Results using this less conventional method of multisession radiosurgery were comparable to those of other radiosurgical techniques. Tumor control was achieved in 96% of patients (38% regressed, 58% stable, 4% enlarged), facial and trigeminal neuropathies each occurred at a rate of 4%, and "hearing was preserved at almost the same level as that prior to radiosurgery in all patients."

The use of LINAC radiosurgery for acoustics is briefly discussed in reports by Delaney et al. (99) and Barcia et al. (100). In addition, fractionated stereotac-tic radiation therapy (SRT) has been used as an alternative management for VS (101,102) This method is proposed as a way of exploiting the precision of stereo-tactic radiation delivery to minimize dose to normal brain, while employing lower fractionated doses in an effort to minimize complications. Thus far, most radiosurgeons have felt that optimal results can be achieved with highly con-formal single-fraction radiosurgery, while sparing the patient the inconvenience of a prolonged treatment course.

Nonacoustic Schwannomas

The vast majority of intracranial schwannomas arise from the myelin sheath of the vestibular branch of the eighth cranial nerve (VS), but nonacoustic schwannomas may originate from the sheaths of cranial nerves V, VII, IX, X, or XI. These are rare skull base tumors that, like their eighth nerve counterparts, are slow growing and noninvasive but frequently problematic owing to involvement of cranial nerves and extension throughout the skull base. They also share many of the characteristics cited for vestibular schwannomas that make them well suited for radiosurgery.

The standard treatment for nonacoustic schwannomas is microsurgical resection. Various surgical approaches have been advocated, and good local control rates are commonly achieved at the expense of significant cranial nerve injuries. Because of the significant morbidity associated with extensive skull base surgery (especially if the lower cranial nerves are involved), the existence of a subset of patients (elderly or medically infirm) in whom surgery is ill advised, and the frequent incidence of incomplete resection, the quest for a safe and effective alternative therapy for these tumors is warranted. Given its success in treating the closely related acoustic schwannoma, radiosurgery seems a natural possibility. Again, Gamma Knife groups have reported success (103,104)

Mabanta et al. (105) reported on 18 patients with nonacoustic schwannomas who were treated with LINAC radiosurgery at the University of Florida. Nine of the tumors were located in the jugular foramen region, seven on the trigem-inal nerve, and two on the facial nerve. Half of these patients had undergone prior subtotal resection. Mean marginal dose was 13 Gy to the 80 or 70% isodose line. During a mean follow-up interval of 32 mo, tumor control was 100% (33% regressed, 67% remained stable, no tumor enlarged). Five patients had improvement of preexisting neurologic deficits. Four complications in three patients included one exacerbation of a preexisting facial palsy, two patients with new onset hearing loss, and one with ataxia. No surgical intervention or prolonged steroid use was necessary for any patient with complications.

Meningiomas

Meningiomas are common tumors that result from proliferation of meningo-thelial cells. They account for approx 20% of primary brain tumors, affect predominantly middle-aged patients, and have a 2:1 predilection for females (106). Like vestibular schwannomas, they are generally noninvasive and pathologically benign and tend to behave indolently, but the natural history of any particular case is unpredictable. Clinical presentation is variable, includes seizures, hemiparesis, visual field loss, aphasia, and other focal findings, and is determined in large part by the location of the tumor (107). Successful outcomes from radiosurgical treatment of vestibular schwannomas and the encouraging results of conventional radiotherapy for meningiomas have led to enthusiasm about radiosurgery as a possible alternative treatment for meningiomas. Gamma Knife reports have appeared in the literature documenting a successful experience (108,109) (Table 3).

Engenhart et al. (110) reported the first detailed series of meningiomas treated radiosurgically. In 1990, in that series, 17 patients were treated with a LINAC-based system (the Fishersystem), to a mean marginal dose of 23 Gy. One patient died from treatment-related complications (herniation from

Table 3

Gamma Knife (GK) Series of Meningioma Cases

Table 3

Gamma Knife (GK) Series of Meningioma Cases

Parameter

Kondziolka et al. (152) Pittsburgh 1991—GK

Subach et al. (108) Pittsburgh 1998—GK (petroclival)

Lunsford et al. (153) Pittsburgh 1998—GK

Nicolato et al. (154) Verona, Italy 1996—GK (skull base)

Austria 1997—GK (skull base)

Steiner et al. (155) Karolinska Institute 1998—GK

No. of patients

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