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Fig. 10. (A) Enhanced MRI shows a right cavernous sinus lesion consistent with meningioma. It was treated with 12.5 Gy to the 70% isodose line, using eight isocenters. (B) Enhanced MRI shows the same lesion 3 yr later. The enhancement is gone and the lesion is barely visible.

delayed unilateral hearing loss, one case of left hemiparesis, and the development of leg weakness and hypoesthesia in another patient. This represents a treatment-related mortality of 1.6% and a morbidity of 3.1%.

Shafron et al. (116) reported on the University of Florida experience. The first 70 patients all followed for more than 2 yr, were analyzed. The group consisted of 54 women and 16 men. The average age was 58 (range 20-80 yr). Indications for radiosurgery were as follows: age > 60 yr (16), failed surgery (32), medical infirmity (1), and patient preference (21). One patient had undergone prior external beam radiotherapy. The mean tumor volume was 10 mL (range 0.6-29 mL), and the mean radiation dose was 12.7 Gy (range 10-20 Gy) applied to the 80% isodose line. Three isocenters (range 1-17) were used on average, and emphasis was placed on delivering dose distributions that conformed closely to the contour of the target lesion. Local control has been achieved in 100% of patients to date, with 44% of tumors displaying appreciable regression on follow-up imaging. Clinically, 7% of patients improved, 91% remained stable, and 2% had a worsening of neurological status.

Radiosurgery may well be the treatment of choice for cavernous sinus menin-giomas (Fig. 10) and meningiomas in other locations where relatively high surgical morbidity may be accepted.

Radiosurgery for Malignant Tumors

Malignant tumors are radiobiologically more amenable to fractionated radiotherapy than benign lesions. Malignancies tend to infiltrate surrounding brain, resulting in poorly definable tumor margins. A priori, these two traits of cere-

Fig. 11. (A) Enhanced MRI shows a solitary posterior left frontal metastatic brain tumor. This lesion was treated with 20 Gy to the 80% isodose line, using one isocenter. (B) Enhanced MRI shows the same lesion 9 mo later. Metastatic lesions are usually rapidly controlled with stereotactic radiosurgery.

Fig. 11. (A) Enhanced MRI shows a solitary posterior left frontal metastatic brain tumor. This lesion was treated with 20 Gy to the 80% isodose line, using one isocenter. (B) Enhanced MRI shows the same lesion 9 mo later. Metastatic lesions are usually rapidly controlled with stereotactic radiosurgery.

bral malignancies would seem to make radiosurgery an unattractive treatment option. Nevertheless, SRS is proving to be a useful weapon in the armamentarium against malignant brain tumors. The most common applications of SRS to malignant tumors are the treatment of cerebral metastases and the delivery of an adjuvant focal radiation "boost" to malignant gliomas.

Cerebral Metastases

Unlike most cerebral malignancies, metastatic tumors tend to be pseudo-encapsulated, without substantial microscopic peripheral spread. This permits the use of the characteristically tight margins used in radiosurgery, without undo risk of marginal recurrence. Brain metastases also tend to be spherical and clearly delineated on gadolinium-enhanced MRI. This makes them convenient radiosurgical targets. Most importantly, a large body of literature supports the assertion that radiosurgery is a relatively inexpensive, minimally invasive, safe, and effective way to control local tumor progression and prolong survival in patients with cancers that have metastasized to the brain (Fig. 11).

Sturm et al. (117) published the first report on radiosurgical treatment of brain metastases in 1987. This group used a LINAC-based radiosurgery system to treat 12 patients with deep brain metastases and noted arrest of tumor growth, shrinkage of tumor, decreased enhancement, and loss of peritumoral edema in various patients. One patient, with a large posterior fossa metastasis, died shortly after treatment, but the remainder experienced no untoward side effects and a "marked, sometimes dramatic improvement of the clinical condition, beginning a few days after irradiation." The authors proposed that radio-

surgery was a valuable tool in the treatment of inoperable, radioresistant brain metastases.

Since that time, many reports on LINAC and Gamma Knife radiosurgery for metastatic tumors have appeared in the literature (118-124). A few of the larger series are reviewed here (Tables 5 and 6).

Alexander et al. (125) reported 1- and 2-yr actuarial local control rates of 85 and 65% for a series of 248 patients. The median tumor volume was 3 mL, and the median tumor dose was 15 Gy. The median survival was 9.4 mo.

A multiinstitutional analysis by Auchter et al. (126) retrospectively examined a group of 122 patients who had undergone SRS for single metastases. Patients were selected to match those enrolled in the earlier study of Patchell's et al. (127) of surgery vs surgery plus whole brain radiotherapy. Selected patients had single metastases, no prior surgery or whole body radiation therapy, age >18 yr, a surgically resectable lesion, Karnofsky performance scores >70, and nonra-diosensitive histology. Treatment was carried out on a LINAC-based radiosurgery system, and the median dose to the tumor margin was 17 Gy (range 10-27 Gy). Nearly all patients also underwent whole body radiation therapy. Local control was 86%. Actuarial 1- and 2-yr survival was 53% and 30%.

Joseph et al. (128) reported on 120 patients treated with LINAC radiosurgery. Median survival was 32 wk. Patients with one or two metastases had equivalent survival times. Patients with three or more metastases had a significantly shorter survival time (14 wk). This group (Stanford) has published several other papers on this issue (129,130).

Valentino et al. (131) reported on the treatment of 86 patients. Shrinkage or disappearance of lesions was seen in 80% of cases, but some required repeat radiosurgery. The median survival was 43 wk for patients treated with radio-surgery alone. Unpublished data from the University of Florida experience are reported in Table 2.

Malignant Gliomas

Malignant gliomas account for about 40% of the approx 17,000 new cases of primary central nervous system tumors in the United States every year, and an exceptionally high fatality rate makes their clinical impact dramatic. Glioblas-toma multiforme (GBM) accounts for roughly 80% of malignant gliomas and has an annual incidence of over 5000 cases. The natural history of untreated GBM results in a median survival of 3 mo. With current standard therapy (resection plus conventional fractionated radiotherapy), median survival is typically 9-10 mo, with a 5-yr survival of about 5%. Similarly, 5-yr survival for anaplastic astrocytoma (AA) is typically under 20%.

Malignant gliomas rarely metastasize, and mortality is primarily attributed to nearly universal local failure. It has been demonstrated that more than 80% of failures occur within 2 cm of the primary tumor. Therefore, modern investigations are understandably focused on achieving local control in an attempt to improve the overall outcome in patients with malignant glioma. Various modalities, including radiation sensitizers, unconventional fractionation schemes, heavy particle radiotherapy, hyperthermia, interstitial brachytherapy,

Table 5

Gamma Knife (GK) Series: Metastatic Brain Tumors

Parameter

Kim (156) Pittsburgh GK 1997

Shiau (157) UCSF GK 1997

Rand (158) John Wayne Ca Inst GK 1995

Kida (159) Komaki,

Japan GK 1995

Flickinger (160) Multiinstitution GK 1994

Kihlstrom (161)

Karolinska Inst., Sweden GK 1993

No. of patients

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