Neoadjuvant Hypofractionated Radiotherapy and Chemotherapy for Extremity Soft Tissue Sarcomas: Safety, Feasibility, and Early Oncologic Outcomes of a Phase 2 Trial.

Background and purpose Optimal treatment of extremity soft tissue sarcomas (ESTS) is controversial. The aim of this study was to evaluate neoadjuvant chemotherapy plus concomitant hypofractionated RT (hypo-RT) in local and distant disease relapse. Here we report safety, feasibility and early outcomes. Materials and methods This was a prospective, single arm study with a goal accrual of 70 patients. Between 2015 and 2018, 18 patients with histologically confirmed nonmetastatic ESTS were assigned to receive doxorubicin and ifosfamide for three neoadjuvant cycles, concomitant with hypo-RT (25Gy in 5 fractions) followed by surgery. The primary endpoint was disease-free survival (DFS). Secondary outcomes were pathologic response, wound complications (WC), and morbidity rates. Results Median follow-up was 29 months. At last follow-up, 13/18 patients were alive without evidence of local or systemic disease (DFS 72%), 1 had died due to metastatic disease, and 3 were alive with distant metastasis. One patient presented with local relapse within the irradiated field. Mean DFS time was 48.6 months (95% CI: 37.3 - 59.9). Six patients (33.3%) had no residual viable tumor detected in pathologic specimens (3 of these myxoid liposarcomas). There was a significant difference in WC among patients with acute RT skin toxicity. Six patients (33.3%) developed major WC. No grade 3 or 4 ChT adverse events were reported. Conclusion Despite the limited sample size, these early outcomes demonstrate that this treatment regimen is feasible and well tolerated with high rates of limb preservation, local control, and pathologic complete response, supporting further investigation in a multi-institutional setting. Trial registration ClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654.