Hypofractionated Preoperative RT May Be Safe And Effective in Soft Tissue Sarcoma

Study findings have show that hypofractionated preoperative radiotherapy may be safe and effective, among patients with soft tissue sarcomas.

Among patients with soft tissue sarcomas (STS), study findings have shown that hypofractionated preoperative radiotherapy (RT) may be safe and effective.

While severe side effects that develop after a significant period of time affect a minority of patients, these late side effects decrease over time. Additionally, everyday activity function and health-related quality of life appear to improve with more time from combined medical treatment.

The local recurrence‐free survival rate (percentage of patients free of cancer recurrence at the local site where the tumor formed) was 93% over four years, according to findings published in Cancer.

As of March 2024, with a median follow-up of 43 months, 13% of patients had died. The four-year overall survival (the time patients live, regardless of disease status) rate was 89%, and sarcoma-related deaths accounted for 9% of all deaths, resulting in a four-year disease-specific survival rate of 92%. Regarding local recurrence, the four-year local recurrence-free survival rate was 93%, with 6% of patients experiencing local recurrence at a median of 16 months. Distant metastasis occurred in 19% of patients, primarily to the lungs, at a median time of seven months, leading to a four-year distant metastasis-free survival rate of 80%.

The rate of grade grade 2 (moderate) or higher RT-related late toxicities (RT-induced side effects) at two years was low (eight of 88 patients), and they tended to improve with time. The late toxicities included 2% grade 2 or higher skin toxicity, 2% fibrosis (thickening and scarring of connective tissue), 3% lymphedema (swelling caused by fluid buildup), 1% joint stiffness and 3% bone fractures.

At two years, 51% of patients had any late toxicity (grade 1 [mild], 82%), down from 79% at six to 12 months. The highest rate of grade 2 or higher RT-related toxicities occurred within the first year (14%), with a decline to 9% at two years. Grade 3 (severe) toxicities were uncommon, occurring in 4% of patients, primarily as femur fractures that occurred at a median of 17 months and lymphedema in one patient. One patient had a grade 4 (life-threatening) skin toxicity, which was a severe late effect following an acute major wound complication.

Both functional outcomes and quality of life improved over time following treatment, as assessed by the Musculoskeletal Tumor Society Rating Scale and the Functional Assessment of Cancer Therapy-General, respectively. At the two-year follow-up, both measures were significantly better than baseline.

A single-center, open-label, prospective phase 2 clinical trial, HYPORT-STS, was conducted between 2018 and 2021. The trial enrolled 119 eligible adult patients, median age of 60 years, with localized STS of the limbs or outer layer of the torso. Patients underwent a three-week course of preoperative RT followed by surgery four to eight weeks later. Results and follow-up were analyzed from the date of surgery.

The most common histologies (subtypes) included undifferentiated pleomorphic sarcoma (26 patients), followed by myxoid liposarcoma and other liposarcomas (17 and 15 patients, respectively), and myxofibrosarcoma (15 patients). The lower extremity (below the waist) was the most common tumor location (78 patients), with a median tumor size of 7.5 cm. Approximately one third of patients (41 patients) had undergone prior nononcologic excision (surgery to remove non-cancerous cells) without remaining cancer tissue at the time of study enrollment.

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