A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma

Abstract

In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma.Patients and Methods: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization.Results: Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area.Conclusions: A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.

Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall: Results of a Single-Arm Prospective Clinical Trial

“…The rate of grade ≥2 radiation-associated toxicity (fibrosis, joint stiffness, or lymphedema) after median follow-up of two years was tolerable (16%). The oncology outcomes are good with a 5.7% rate of local recurrence after surgery [34]. In our current study the rate of late morbidity was also relatively low, with 13.8% of long-term radiation-induced toxicity.…”

Coronavirus Disease (COVID-19) Outbreak: Hypofractionated Radiotherapy in Soft Tissue Sarcomas as a Valuable Option in the Environment of Limited Medical Resources and Demands for Increased Protection of Patients

“…Data presented in the Table 1 suggest that this assumption may be correct because local control in all described regimens is higher than 80% despite various EQD2. Interestingly, HFRT regimen described by Koseła-Paterczyk et al (25 Gy in 5 fractions) given in the majority of patients without preoperative chemotherapy provided lower (but acceptable) local control than regimens with higher fraction and total doses (30 Gy in 5 fractions) or one with the same fractionation regimen but combined with sequential anthracycline-based chemotherapy (5,27,30,31). The same 5 × 5 Gy regimen without chemotherapy but with delayed surgery resulted in 100% 1-year control rate in patients with myxoid liposarcomas that are considered radiosensitive (29).…”

“…Preoperative HFRT in STS has been validated in retrospective analyses, prospective registries, and phase I-II clinical trials (5,(23)(24)(25)(26)(27)(28)(29)(30)(31). However, randomized phase III trials comparing preoperative CFRT with HFRT are lacking.…”

Early Outcomes of Preoperative 5-fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection

“…https://doi.org/10.1101/2020.03.20.20038885 doi: medRxiv preprint of incisional wound vacuums. 13 This can be compared to the historical standard 5-year local control of 93%. 1 Table ??…”