3-Week Course of Radiotherapy May Offer Greater Convenience for Patients With Soft Tissue Sarcoma

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Moderately hypofractionated preoperative radiotherapy did not increase risk for major wound complication in patients with soft tissue sarcomas, according to findings from the single-arm, phase 2 trial HYPORT-STS.

Moderately hypofractionated preoperative radiotherapy did not increase risk for major wound complication in patients with soft tissue sarcomas, according to findings from the single-arm, phase 2 trial HYPORT-STS (NCT03819985). Investigators argued that the 3-week course of treatment is more convenient for patients than the standard 5-week course.

In the open-label trial conducted at The University of Texas MD Anderson Cancer Center, 120 adults with nonmetastatic soft tissue sarcomas of the extremities or superficial trunk received preoperative radiotherapy to a dose of 42.75 Gy in 15 fractions of 2.85 Gy per day for 3 weeks.

The standard preoperative radiotherapy regimen in this patient population is 50 Gy delivered in 25 fractions for 5 weeks.

The median postoperative follow-up was 24 months (IQR, 17-30). Thirty-seven patients (31%; 95% CI, 24%-40%) developed a major wound complication at a median time of 37 days (IQR, 25-59) after surgery. Among those 37 patients, 12 (32%) required a second operation to addressed major wound complication

The primary end point for the study was development of major wound complication within 120 days of surgery. Historically, 35% of patients develop major wound complications at that point.

Major wound complications were defined as those requiring a secondary operation or operations under general or regional anesthesia for wound treatment, readmission to the hospital for wound care, invasive procedures for wound care, deep wound packing to an area of wound measuring at least 2 cm in length, prolonged dressing changes, repeat surgery for revision of a split thickness skin graft, or wet dressings for longer than 4 weeks.

The median age of enrolled patients was 60 years (range, 48-69) and 58% were men. Sixty-five percent had a tumor of the lower extremity, 18% had tumors of the trunk, and 17% had tumors of the upper extremity. The most common tumor histopathologies were unclassified pleomorphic sarcoma (22%), myxoid liposarcoma (14%), non-myxoid liposarcoma (13%), and myxofibrosarcoma (13%).

Almost half of all patients received intensity-modulated or volumetric-modulated arc radiotherapy (48%) and three-dimensional conformal radiotherapy (46%). Surgical resection occurred at a median interval of 5.7 weeks (IQR, 4.6-6.4) following the last fraction of radiotherapy. All patients had an ECOG performance status of 0 to 3, including 94% of patients who had an ECOG performance status of 0 or 1.

All patients received preoperative radiotherapy during a median time of 20 days (IQR 18-21). Eighty-eight (73%) patients had intermediate- or high-grade tumors. A sarcoma surgeon closed the wound for 25 patients (21%) using primary closure, while 95 patients (79%) had a plastics or reconstructive surgical specialist participate in their wound closure, having a wound closure with a vascularized tissue transfer, split thickness skin grafting, or both; or an otherwise complex closure.

One, 8, and 28 patients had major wound complications in the upper extremity, in the trunk, and in the lower extremity, respectively. Of those 28, 23 (82%) were proximal and 5 (18%) were distal.

Eight other patients had a wound complication that was not considered major by the primary end point criteria. Those included patients who had wound-edge necrosis requiring silver sulfadiazine cream for healing (n = 1), those requiring prolonged dry dressing (n = 4), and those who were treated with oral antibiotics (n = 3). Overall, 45 patients (38%) had a wound complication of any severity.

In univariate analysis, patients with upper extremity were significantly less likely to develop major wound complications compared with patients with lower extremity or trunk tumors. Additionally, patients with diabetes were significantly more likely to develop major wound complications than patients without diabetes.

Investigators did not find a significant correlation between development of a major wound complication and age, sex, body-mass index, tobacco smoking status, ECOG performance status, prior excisional procedure, tumor size, primary or recurrent presentation, radiotherapy technique, the time between radiotherapy and surgery, the final surgical resection margin, or the receipt of chemotherapy. There was also no difference in the development rate of major wound complications and surgical specialty.

No patient had acute radiation toxicity of grade 3 or higher, defined as toxicity that developed during radiotherapy or within 4 weeks of the radiotherapy end date. Additionally, no patients experienced an on-treatment serious adverse effect. Four (3%) patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3. There were no treatment-related deaths.


Guadagnolo BA, Bassett RL, Mitra D, et al. Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial. Lancet Oncol. Published online November 4, 2022. doi:10.1016/S1470-2045(22)00638-6

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