Femoral Fracture in Primary Soft Tissue Sarcoma Treated with Intensity-Modulated Radiation Therapy with and Without Dose

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ORIGINAL ARTICLE – SARCOMA

Femoral Fracture in Primary Soft Tissue Sarcoma Treated with Intensity-Modulated Radiation Therapy with and Without Dose Constraints Dana L. Casey, MD1, Sean L. Berry, PhD2, Aimee Crago, MD3, Nicola Fabbri, MD3, Samuel Singer, MD3, and Kaled M. Alektiar, MD1 1

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; 2Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY; 3Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

ABSTRACT Background. We previously reported that the cumulative risk of femoral fracture in patients treated with intensitymodulated radiation therapy (IMRT) for thigh and groin soft tissue sarcoma (STS) is low. In the current study, we sought to evaluate the effect of radiation dose constraints on the rate of femoral fracture in a more contemporary cohort. Methods. All patients treated with IMRT for STS of the thigh or groin from 2004 to 2016 were included (n = 145). Beginning in 2011, radiation dose was constrained to a mean dose of\ 37 Gy, volume of bone receiving C 40 Gy (V40Gy) \ 64%, and maximum dose \ 59 Gy to limit the dose to the femur. Results. Sixty-one patients were treated before dose constraints were implemented, and 84 patients were treated after. Median follow-up for patients treated before and after constraints were implemented was 6.1 and 5.7 years, respectively, and the two groups were demographically and clinically similar. On univariate analysis, the 5-year cumulative incidence of femoral fracture among patients treated with and without dose constraints was 1.8% (95% confidence interval [CI] 0.3–12.2%) versus 7.4% (95% CI 3.1–17.6%) [p = 0.11, p = non-significant, respectively].

 Society of Surgical Oncology 2020 First Received: 28 July 2020 Accepted: 17 September 2020 K. M. Alektiar, MD e-mail: [email protected]

On multivariable analysis, only age C 60 years was significantly associated with increased risk of fracture. Conclusions. The risk of femoral fracture after IMRT for STS of the thigh/groin is low, and with the implementation of radiation dose constraints, the risk is \ 2%. Although longer follow-up is needed, our results support the utilization of extremity sarcoma IMRT-specific dose constraints for fracture prevention. Keywords Extremity sarcoma  Femur  IMRT  Fracture  Dose constraints Standard treatment for soft tissue sarcoma (STS) of the extremity involves limb-sparing surgery with either preoperative or postoperative radiation. Although this combination results in excellent local control and survival, radiation-associated femoral fractures remain one of the more serious and disabling consequences of radiation for extremity STS, with an incidence of approximately 10%.1–4 The rate of radiation-induced femoral fractures is affected by clinical and treatment factors such as age, sex, tumor location, extent of periosteal stripping at the time of resection, receipt of chemotherapy, and radiation dose.1,5 Of these factors, radiation dose to the fem