Long-term real-world outcomes following preoperative radiotherapy and conservative surgery for trunk and extremity soft tissue sarcomas: a retrospective cohort study.

Background: Radiotherapy (RT) combined with surgery is standard of care for most soft tissue sarcoma (STS) of the extremity and trunk. Preoperative RT is often preferred because it enables a lower radiation dose and is associated with more favorable late toxicity profiles. We report real-world, long-term oncological, toxicity, and functional outcomes of patients treated with preoperative RT at a sarcoma reference center. Methods: We did a retrospective analysis of data from our prospectively maintained database (data collected from April 1989 to November 2020) from a single sarcoma center in Canada. We included patients with histologically confirmed STS of extremity or trunk. Eligible patients received preoperative RT with either 2D/3D-Conformal Radiation Therapy (3D-CRT) or Intensity Modulated Radiation Therapy (IMRT), followed by surgery 4-6 weeks later. Local and oncological outcomes were assessed. Long-term toxicities were graded using the RTOG late toxicity scoring criteria. The Musculoskeletal Tumor Society Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) evaluated functional outcomes. Further study endpoints included the occurrence of distant metastases (DM) and overall survival (OS), stratified by histology. Findings: Among 1027 patients (370 3D-CRT, 657 IMRT), the median follow-up was 5.9 years (range: 0.5-24.6 years). Major wound complications occurred in 28% with 3D-CRT and in 21% with IMRT (p = 0.09). The 5-year cumulative rates of local recurrence (LR) and distant metastasis were 5.2% vs. 5.4% and 25.5% vs. 25.6%, with a 5-year overall survival of 79.3%. None of these outcomes differed significantly between 3D-CRT and IMRT. Grade ≥2 late toxicity occurred in 25% (30% in 3D-CRT and 22% in IMRT), including fibrosis (17%), skin toxicity (9%), joint stiffness (6%), and edema (9%). IMRT was associated with significantly lower rates of grade ≥2 skin toxicity (OR 0.28), subcutaneous fibrosis (OR 0.55), and joint stiffness (OR 0.49) compared to 3D-CRT. Functional outcomes were comparable between IMRT and 3D-CRT. Patients with grade ≥2 toxicities had lower functional scores (p < 0.001). Interpretation: In this large cohort with mature follow-up, long-term local control and function were excellent with low rates of high-grade toxicity. Modern RT techniques were associated with less late toxicity without compromising local control, but acute wound complications and distant metastases remain ongoing challenges. Funding: None.