High Dimension

3-Week Hypofractionated Preoperative Radiation Therapy for Patients with Soft Tissue Sarcomas (HYPORT-STS): A Single-Center, Open-Label, Single-Arm Phase 2 Trial

Background

The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions over 5 weeks for soft tissue sarcomas provides excellent local control, with major wound complications occurring in approximately 35% of patients. Our aim was to investigate the safety of a moderately hypofractionated, shorter radiotherapy regimen, which may be more convenient for patients.

Methods

This single-center, open-label, single-arm Phase 2 trial (HYPORT-STS) was performed at a single tertiary cancer center (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy at a dose of 42 75 Gy in 15 fractions of 2 85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0 to 3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anesthesia for wound treatment; readmission to hospital for wound care; invasive wound care procedures; a deep dressing over a wound area measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision split-thickness skin graft; or wet dressings for more than 4 weeks. We analyzed our primary outcome and the safety of all enrolled patients. We monitored safety using a one-arm Bayesian stopping rule simulator comparing the rate of major wound complications at 120 days after surgery in study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete and follow-up is ongoing.

Results

Between December 18, 2018 and January 6, 2021, we assessed the eligibility of 157 patients, of whom 120 were recruited and received preoperative hypofractionated radiotherapy. At no time did the calculation of the stopping rule indicate that the trial had to be stopped prematurely for lack of safety. The median postoperative follow-up was 24 months (IQR 17–30). Of 120 patients, 37 (31%, 95% CI 24–40) developed a major wound complication within a median of 37 days (IQR 25–59) after surgery. No patient experienced acute radiotoxicity (during radiotherapy or within 4 weeks of the end date of radiotherapy) grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or a serious adverse event during treatment. Four (3%) of the 115 patients had late radiotoxicity (≥ 6 months after surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphedema (n=1) and skin ulceration (n=1). There were no treatment-related deaths.

Interpretation

Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and therefore may be a more practical alternative to conventional fractionated radiotherapy. Patients can be advised on these results and possibly be offered this regimen, especially if it facilitates management in a specialty center for sarcomas. Results on long-term oncological outcomes, late toxicity and functional outcomes are awaited.

Funding

The National Cancer Institute.