(P 314) PRE-OPERATIVE RADIATION THERAPY INCREASES ADHERENCE IN PATIENTS WITH HIGH-RISK EXTREMITY SOFT TISSUE SARCOMA

Objective: Based on guidelines from the National Comprehensive Cancer Network (NCCN), treatment for extremity soft tissue sarcoma (ESTS) should include radiation therapy (RT) and surgical resection with negative margins for tumors that are high grade and >5 cm. Radiation has been demonstrated to reduce the risk of local recurrence and amputation for ESTS and, in a few studies, cancer specific survival. The recommended dose for pre-operative radiation therapy is 50 Gy while the recommended dose for post-operative radiation therapy is 60 Gy. Patients receiving less than the recommended doses of RT are at greater risk of local recurrence. RT is time and labor intensive for patients and social determinants of health may affect adherence, which may lead to poor patient outcomes. Whether sequencing of radiation therapy for patients with ESTS can be leveraged to improve compliance remains unknown. Therefore, the aim of this study was to define factors associated with completion of RT and to determine if pre-operative RT improved adherence compared to post-operative RT.

Methods: The analytic cohort was restricted to patients from 2004 to 2020 in the National Cancer Database with high grade ESTS >5 cm without nodal or distant metastases who received limb-sparing surgery and RT with R0 margins. A multivariable logistic regression analysis identified factors associated with RT adherence defined according to NCCN guidelines. Variables in this model included radiation sequence (pre-operative, post-operative), distance from treating facility, facility type, facility region, age at diagnosis, primary payor, race, ethnicity, resection (local excision, radical resection), median income, and tumor size. A multivariable Cox Proportional Hazards model was used to assess overall survival. Independent variables in this model included radiation sequence (pre-operative, post-operative), distance from treating facility, facility type, facility region, age at diagnosis, primary payor, race, ethnicity, resection (local excision, radical resection), median income, tumor size, chemotherapy, histologic subtype, year of diagnosis, and Charlson-Deyo Comorbidity Index.

Results: Among 2327 patients, 47.7% received pre-operative RT (n=1111) and 51.9% (n=1207) received post-operative RT. A greater proportion of patients treated with pre-operative RT (51.9%) received the recommended dose of RT versus patients treated with post-operative RT (48.1%, n=787, p< 0.0001). Patients with private insurance (50.4% vs. 49.6%, p=0.027) and individuals treated at an academic medical center (53.9% vs. 46.1%, p< 0.001) were more likely to receive pre-operative RT. On multivariable analysis, patients who received pre-operative RT had lower odds of receiving an insufficient dose of RT (OR 0.34 [95% CI 0.26-0.45]). No differences in radiation therapy sequencing were observed by age, sex, income, education, urban/rural residence, or comorbidities (all p>0.05). Neither RT adherence nor radiation sequencing (post-operative RT vs. pre-operative RT) were independent predictors of overall survival.

Conclusion: There are multiple potential explanations for lower adherence to post-operative RT as compared to pre-operative RT. First, post-operative RT is a longer course of therapy, 6-6.5 weeks as opposed to 5 weeks, and therefore poses more substantial access and logistical barriers than pre-operative RT. Second, the higher dose of RT and larger field sizes required for post-operative RT, as compared with pre-operative RT, also creates more acute side effects (radiation dermatitis, acute edema, pain, etc.) that could motivate premature treatment discontinuation. There also may be a temptation for patients in a post-operative RT scenario to forego any further post-surgical treatment. Patients with large, high-grade ESTS who receive RT in the pre-operative RT setting are more likely to complete therapy and receive an optimal dose of RT compared to post-operative RT. The use of pre-operative RT improves adherence and should be widely considered in patients with high-grade ESTS, particularly in patients at risk for not completing therapy.