Hypofractionated 3-Week Course of Preoperative Radiotherapy for Soft-Tissue Sarcomas

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In a single-center phase II trial (HYPORT-STS) reported in The Lancet Oncology, Guadagnolo et al found that a hypofractionated 3-week course of preoperative radiotherapy was safe in patients with soft-tissue sarcomas and may serve as an alternative to conventionally fractionated radiotherapy in this setting.

As stated by the investigators, “The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft-tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients.”

Study Details

In the study, 120 eligible patients with nonmetastatic soft-tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0 to 3 were enrolled at The University of Texas MD Anderson Cancer Center between December 2018 and January 2021. Patients received preoperative radiotherapy at up to 42.75 Gy in 15 fractions of 2.85 Gy/day for 3 weeks (5 fractions per week); radiotherapy was delivered by radiation oncologist choice of conventional 3D radiotherapy or intensity-modulated radiotherapy techniques.   

The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring secondary operation(s) under general or regional anesthesia; readmission to the hospital for wound care; invasive procedures for wound care without a secondary operation; deep wound packing to wound area ≥ 2 cm in length; prolonged dressing changes; repeat surgery for revision of split thickness skin graft; or wet dressings for longer than 4 weeks. A safety stopping rule specified that the trial would be halted if the proportion of patients with a major wound complication exceeded the historical rate of 35%.  

Moderately hypofractionated preoperative radiotherapy delivered to patients with soft-tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy.
— Guadagnolo et al

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Key Findings

The incidence of major wound complications did not trigger the stopping rule at any point during the study.

Median postoperative follow-up was 24 months (interquartile range [IQR] = 17–30 months).

A major wound complication developed in 37 (31%, 95% confidence interval [CI] = 24%–40%) of 120 patients within 120 days after surgery. Median time to development of wound complications was 37 days (IQR = 25–59 days) after surgery. Complications consisted of invasive procedures without a secondary operation in 13% of patients, secondary operation(s) in 10%, hospital readmission in 6%, and deep wound packing in 2%.

No patients had grade ≥ 3 acute radiation toxicity (up to 4 weeks after end of radiotherapy); grade 1 or 2 events consisted of skin toxicity in 72% (8% grade 2), fatigue in 43% (2% grade 2), and pain in 39% (11% grade 2). No patients had on-treatment serious adverse events. Among 115 patients with data available, 4 (3%) had grade ≥ 3 late radiation toxicity (≥ 6 months postsurgery), consisting of femur fracture in 2, lymphedema in 1, and skin ulceration in 1. No treatment-related deaths occurred.

Among 119 patients evaluable for local disease control, local relapse had occurred in 6 (5%; 4 in the radiotherapy field, 1 at field edge, and 1 outside the field); median time to relapse after surgery was 16 months (IQR = 7–17 months). Actuarial 30-month local recurrence–free survival was 93% (95% CI = 86%–97%).

The investigators concluded, “Moderately hypofractionated preoperative radiotherapy delivered to patients with soft-tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counseled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty center. Results on long-term oncological, late toxicity, and functional outcomes are awaited."

B. Ashleigh Guadagnolo, MD, of the Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit

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