Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma

Eashwar Somasundaram; Timothy D Smile; Ahmed Halima; James B Broughman; Chandana A Reddy; Shireen Parsai; Jacob G Scott; Chirag Shah; Timothy Chan; Shauna Campbell; Lilyana Angelov; Peter M Anderson; Stacy Zahler; Matteo Trucco; Stefanie M Thomas; Shavaughn Johnson; Nathan Mesko; Lukas Nystrom; Dale Shepard; George Thomas Budd; Peng Qi; Anthony Magnelli; Erin S Murphy

Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma

J Radiosurg SBRT. 2022;8(4):265-273.

Authors

Eashwar Somasundaram¹, Timothy D Smile², Ahmed Halima², James B Broughman², Chandana A Reddy², Shireen Parsai³, Jacob G Scott², Chirag Shah², Timothy Chan², Shauna Campbell², Lilyana Angelov⁴, Peter M Anderson⁵, Stacy Zahler⁵, Matteo Trucco⁵, Stefanie M Thomas⁵, Shavaughn Johnson⁵, Nathan Mesko⁶, Lukas Nystrom⁶, Dale Shepard⁷, George Thomas Budd⁷, Peng Qi², Anthony Magnelli², Erin S Murphy^{2

4}

Affiliations

¹ Case Western Reserve University School of Medicine, Cleveland, OH, USA.
² Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
³ Department of Radiation Oncology, Ohio Health Riverside Methodist Hospital, Columbus, OH, USA.
⁴ Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA.
⁵ Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic, Cleveland, OH, USA.
⁶ Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, OH, USA.
⁷ Department of Hematology and Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.

PMID: 37416333
PMCID: PMC10322177

Abstract

Introduction: Stereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology.

Methods: 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 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/β ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology.

Results: Forty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive (n = 63), and all other histologies were classified as radioresistant (n = 75). 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- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies (p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED (p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies (p = 0.25).

Conclusion: There is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.

Keywords: SBRT; Sarcoma; biological effective dose; dose; local control.