Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities

Soft tissue sarcomas (STS) comprise a diverse group of mesenchymal malignancies that require multidisciplinary care. Although surgery remains the primary form of treatment for those with localized disease, radiation therapy (RT) is often incorporated either in the neo- or adjuvant setting. Given the development of modern RT techniques and alternative dosing schedules, stereotactic ablative radiotherapy (SABR) has emerged as a promising technique. However, the current role of SABR in the treatment of STS of the extremities remains uncertain.This was a single-center, prospective, single-arm phase II trial. Patients with localized STS who were candidates for limb-preservation surgery were included. Experimental treatment consisted of SABR with 40 Gy in 5 fractions, administered on alternate days, followed by surgery after a minimum interval of 4 weeks. The primary outcome was the rate of wound complication. Secondary outcomes included 2-year local control (LC), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) rates (and other toxicities).Twenty-five patients were enrolled between October 2015 and November 2019 and completed the treatment protocol. The median rate of histopathologic regression was 65% (range 0-100) and 20.8% of tumors presented pathologic complete response (pCR). Wound complications were observed in 7/25 patients (28%). Three patients underwent disarticulation by vascular occlusion after plastic reconstruction and one patient was amputated by grade 3 limb dysfunction. After a median follow up of 20.7 months, the 2-year estimated risk of local recurrence, distant metastasis and cause-specific death were 0%, 44.7% and 10.6% respectively.Neoadjuvant SABR appears to improve the pCR for patients with eSTS, with acceptable rate of wound complications. Nevertheless, this benefit should be weighed against the risk of late of vascular toxicity with SABR regimen since, even in a short median follow-up, a higher rate of amputation than expected was observed. A larger sample size with longer follow-up is necessary to conclude the overall safety of this strategy.