Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin

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Object

The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control.

Methods

Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3–83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134–0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78–92%) in tumors treated with 24 Gy, compared with 49% (CI 30–68%) in tumors treated with 18 Gy and 45% (CI 23–67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin.

Conclusions

Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

Abbreviations used in this paper:ANOVA = analysis of variance; CI = confidence interval; HR = hazard ratio; KPS = Karnofsky Performance Scale; MTD = maximal tolerated dose; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy.

Article Information

Address reprint requests to: Michael A. Vogelbaum, M.D., Ph.D., Brain Tumor Institute and Department of Neurosurgery, ND40, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. email: vogelbm@neus.ccf.org.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Kaplan–Meier curves of time to local treatment failure, stratified by SRS dose. A tumor margin dose of 24 Gy had a significantly longer time to local failure than in the 15- and 18-Gy groups (p = 0.0005; HR 0.277, CI 0.134–0.573).

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    Kaplan–Meier analysis of survival time, using minimal dose for each patient. In this analysis, if a patient had multiple lesions, the dose was set to correspond to the smallest one used for SRS. The analysis was similar to that for time to local control. No statistically significant difference was found among the treatment groups (p = 0.9364).

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    Kaplan–Meier analysis of survival time, using MTD for each patient. In this analysis, if a patient had multiple lesions, the dose was set to correspond to the largest one used for SRS. The analysis was similar to that for time to local control. No statistically significant difference was found among the treatment groups (p = 0.5362).

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