Cleveland Clinic Lerner College of Medicine Cleveland, OH
C. A. Fan1, L. Nystrom2, N. Mesko3, Z. S. Mayo4, Z. D. Burke3, C. S. Shah4, S. A. Koyfman5, J. G. Scott6, and S. R. Campbell3; 1Cleveland Clinc, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 2Department of Orthopaedic Surgery, Cleveland Clinic Foundation, Cleveland, OH, 3Cleveland Clinic, Cleveland, OH, 4Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 5Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 6Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH
Purpose/Objective(s):Ultra-hypofractionated preoperative radiation therapy (UHRT) offers a drastically shorter treatment course for the management of soft tissue sarcoma (STS); however, there are no prospective studies comparing UHRT with standard fractionation (SRT). In addition to local control, major wound healing complications (MWC) are a significant concern. We sought to compare toxicity and oncologic control in a matched cohort of SRT and UHRT patients. Materials/
Methods: In this IRB-approved study, we included patients with STS of the extremity, pelvis, or trunk who were treated with preoperative RT followed by surgical resection. Patients received either SRT (50 Gy at 2 Gy per fraction) or UHRT (=30 Gy at 6 Gy per fraction) between 2006-2023 with IMRT. The cohorts were matched based on tumor location and type of surgical closure. Patients with SRT went to resection 3-6 weeks after RT and UHRT was 0-7 days. An inverse propensity weighting (IPW) method was used to balance covariates between groups. Outcomes included MWC, defined by O’Sullivan, acute and late toxicity, and disease control. Results: Of 132 patients treated with preoperative RT, 37 SRT patients were matched with 37 UHRT patients. 12 patients in each group had tumors located in the arms/shoulders or trunk, and 25 in the leg/external pelvis. The majority underwent primary closure (26 each). Median follow-up time was 29.00 [IQR 13.00, 43.00] and 21.00 [IQR 11.00, 45.00] months in SRT and UHRT, respectively. Patient age, history of diabetes and smoking did not differ between cohorts. UHRT had a higher proportion of grade 3 tumors (p = 0.001) and R1 margin (p=0.042). For acute toxicity, SRT experienced higher rates of grade 1 fatigue (p=0.012) and dermatitis (p=0.001). MWC was 29.7% in SRT vs 44.4% in UHRT (p=0.289). On linear regression, MWC (OR 1.9, 95% CI 0.97-3.76, p=0.06) and wound dehiscence (OR 3.91, 95% CI 1.81-8.73, p=0.0006) were more common in UHRT compared with SRT. Late toxicity (grade =2 fibrosis, joint stiffness, or edema) did not differ significantly. There was no difference in local failure (5.4% SRT vs 2.7% UHRT, p=1.00). Patients with any MWC had an increased risk (OR 5.766, 95% CI 1.85-19.52, p=0.005) for developing distant metastases. Conclusion: UHRT for STS results in excellent local control; however, in this cohort of immediately resected UHRT, there is a trend of higher MWC. To reduce the risk of positive margin and MWC, we have adopted a standard delayed resection for UHRT patients.
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