Association Between Biologically Effective Dose and Local Control After Stereotactic Body Radiotherapy for Metastatic Sarcoma

Abstract

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is increasingly utilized for treatment of patients with recurrent and metastatic tumors. Considering the relative radioresistance of some sarcoma histologies, SBRT may allow for higher biological effectiveness compared to conventional radiotherapy. We report local control outcomes after SBRT based on radiation dose and histology. <h3>Materials/Methods</h3> From our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 year. Univariate and multivariable Cox proportional hazard model analyses were performed to determine association between SBRT dose, histology, and local control. Small round blue cell sarcomas were classified as more radiosensitive and others as radioresistant histologies. A receiver operating characteristic (ROC) curve was generated to determine optimal biologically effective dose (BED) using a/β of 3 Gy. Local control was compared by SBRT dose using the BED cut point and histology. <h3>Results</h3> Forty-two patients with a total of 138 lesions met inclusion criteria. Median follow up was 9.7 months (range 0.5-34.5). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 30 Gy (range 15-60) in 4 fractions (range 1-5). Sixty-two lesions met criteria for radiosensitive histology while 75 lesions were considered radioresistant. Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1-year local control was 65.3% for radiosensitive and 68.6% for radioresistant histologies (<b>P</b> = 0.49). The ROC cut point for BED was 95 Gy. Local control at 1-year was 75% for lesions receiving ≥ 95 Gy BED, and 46.2% for lesions receiving < 95 Gy BED (<b>P</b> = 0.01). On subgroup analysis, local control by BED ≥ 95 Gy remained significant for radiosensitive histologies (<b>P</b> = 0.013), but was not significant for radioresistant histologies (<b>P</b> = 0.25). Overall survival was 47.6% (95% CI, 34.3-66.1) at 1 year and 39.0% (95% CI, 26.2-58.1) at 2 years, and median survival was 10.8 months. <h3>Conclusion</h3> For patients undergoing stereotactic body radiotherapy for metastatic sarcoma, local control was significantly improved when BED was ≥ 95 Gy for radiosensitive histologies, but was not significant for radioresistant histologies. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.