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and stereotactic radiosurgical boost therapy have shown some promise, and continue to be investigated (132).

The observation that local control and median survival can be extended through dose escalation is the basis for the application of brachytherapy and radiosurgery to malignant gliomas. Although achievable radiation doses with conventional external beam irradiation are limited by induced toxicity to around 70 Gy, the addition of a stereotactically focused boost of radiation allows total cumulative doses in excess of 100 Gy to be delivered to residual focal tumor. Brachytherapy and stereotactic radiosurgery offer similar abilities to deliver a focal radiation boost, but SRS may represent the better of the two solutions because it is noninvasive. SRS is an outpatient procedure that avoids the risks of hemorrhage, infection, and radiation exposure to personnel associated with brachytherapy.

Interpreting results of radiation boost treatments has been problematic because of the inherent selection bias toward smaller, more focal lesions. Shrieve et al. (133) compared radiosurgery boost and brachytherapy. Thirty-two patients were treated with brachytherapy and 86 with radiosurgery. Median survival after brachytherapy was 11.5 mo; after radiosurgery it was 10.2 mo. Fewer patients (22%) required reoperation after radiosurgery than after brachytherapy (44%).

Mehta and colleagues (134) tried to eliminate selection bias using a technique called recursive-partitioning analysis (see next two paragraphs). They found that patients treated with radiosurgery had a 2-yr survival of 28%, when 9.7% would have been "expected."

A multicenter retrospective analysis was performed in an effort to control for prognostic factors and better evaluate the impact of SRS on the survival of patients with malignant gliomas (135). The study evaluated 115 patients with malignant gliomas who were treated with a combination of surgery, external beam radiation therapy, and SRS boost at three different LINAC radiosurgery facilities under similar protocols. Patients were stratified into six prognostic classes based on the recursive partitioning analysis of multiple prognostic factors that had been previously reported by the Radiation Therapy Oncology Group (RTOG) (136). This stratification is based on tumor pathology, patient age, patient's functional status (e.g., Karnofsky performance score-KPS), duration of symptoms, and extent of resection; it offers some control for the multitude of prognostic factors, allowing more direct comparison of results.

After a median follow-up of 91 wk, the 2-yr actuarial survival for the entire cohort of patients was 45%, with a median survival of 22 mo. AA patients had not reached median survival and had a 2-yr survival rate of 72%. The GBM patients had a median survival of 21 m and a 2-yr survival of 38%. When patients from the six different prognostic classes were evaluated, a significant difference in overall survival by class was confirmed (p < 0.001). Compared twitho published RTOG results for similarly stratified malignant glioma patients treated without a stereotactic radiation boost, radiosurgery resulted in longer median survival by 4-20 mo, depending on the prognostic class. This benefit was most pronounced for the patients in the moderate to poor prognos tic classes; minimal benefit was observed for the patients in the more favorable prognostic classes. Although this strongly suggests that radiosurgical boost is advantageous for patients with GBM, little can be inferred from the study regarding the utility of SRS for AA.

Some caution is also indicated when interpreting the GBM results. RTOG results may be worse because much of the treatment was performed prior to the advent of quality neuroimaging. Also, postoperative tumor size, which was found to be highly prognostic in other studies, was not a factor in the RTOG stratification, and the average tumor size was greater for the RTOG patients compared with the SRS cohort. On univariate analysis, however, RTOG prognostic class and KPS were the only significant predictors of survival, excluding tumor size and extent of surgery among other potential factors. RTOG prognostic class was eliminated as an independent predictor of survival on multi-variate analysis, leaving KPS as the only significant independent prognostic factor. In fact, patients with a KPS > 70 enjoyed a 2-yr actuarial survival rate of 51% with a median survival of 24 mo, compared with 2-yr and median survivals of 0 and 9 mo, respectively for patients with a KPS < 70. Overall, the study offers strong evidence that radiosurgical boost confers a survival advantage for patients with GBM. It also suggests that patients in poor prognostic classes (e.g., KPS < 70), who have been excluded as candidates for radiation boost in many series, actually may benefit significantly from this aggressive management.

Other Lesions

Many other brain tumors have been treated, in small numbers, by radio-surgery, including low-grade gliomas (137,138), hemangioblastoma (139,140), nasopharyngeal carcinomas (141-143), germinoma (144), medulloblastoma (145), and pituitary tumors (146) A detailed discussion of these indications is beyond the limits of this chapter.

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