Five-Day Preoperative Radiation Shows Promise for High-Risk Soft Tissue Sarcoma: Study
USA: A shortened five-day course of preoperative radiation therapy may offer a more convenient yet effective alternative to the conventional five-week regimen for patients with high-risk soft tissue sarcoma, according to a new clinical trial published in JAMA Network Open.
The study was led by John Nikitas from the Department of Radiation Oncology at the University of California, Los Angeles, along with colleagues.
Preoperative radiation therapy is a standard component of care for patients with extremity and truncal soft tissue sarcoma, helping improve local tumor control before surgery. However, the traditional approach—delivered over approximately five weeks—can pose significant logistical challenges, particularly for patients who must travel long distances or balance treatment with work and caregiving responsibilities. To address this issue, investigators evaluated whether an ultrahypofractionated regimen delivered over just five days could achieve comparable outcomes without compromising safety.
The phase 2, single-arm, nonrandomized trial enrolled patients with histologically confirmed soft tissue sarcoma of the extremities or trunk who were candidates for standard preoperative radiation followed by surgery. Participants were treated at a single academic center between April 2016 and May 2023 and received a total radiation dose of 30 Gy administered in five fractions before surgery. Patients who received neoadjuvant systemic therapy in the expansion phase were excluded from the current analysis.
A total of 110 patients underwent preoperative radiation and surgical resection. The study population included a substantial proportion of older adults, with 38% aged between 65 and 79 years, and most patients were male. Tumors were predominantly located in the lower extremities, and more than half of the cases involved high-grade disease. Median follow-up exceeded three years overall, allowing assessment of both early and longer-term outcomes.
The study led to the following notable findings:
- At two years of follow-up, fewer than 20% of evaluable patients developed grade 2 or higher radiation-related toxic effects, indicating a generally acceptable safety profile for the five-day preoperative radiotherapy regimen.
- Major wound complications were observed in 30% of patients, a frequency comparable to rates reported with conventional, longer-course preoperative radiation therapy.
- Delayed wound healing was noted as a key concern, with wound closure taking longer than six months in about 14% of patients, particularly among those who underwent local tissue advancement flap procedures.
- Oncologic outcomes remained favorable despite wound-related issues, with the two-year local control rate exceeding 92%, reflecting durable tumor control similar to standard preoperative radiation approaches.
- Serious skeletal adverse events, including fractures and amputations, were infrequent during the follow-up period.
The authors noted several limitations, including the single-institution design and the lack of randomization, which may affect generalizability. In addition, physician-reported toxicity grading can vary, and the study did not evaluate outcomes in patients receiving chemotherapy or immunotherapy alongside radiation.
Overall, the findings suggest that a five-day preoperative radiation approach may provide favorable long-term tumor control with manageable toxicity for selected patients with high-risk soft tissue sarcoma. While the shorter schedule could substantially improve treatment accessibility and patient convenience, the investigators emphasized the need for randomized trials to better define its impact on wound healing and to directly compare it with conventional and moderately hypofractionated regimens.
Reference:
Nikitas J, Kendal JK, Savjani RR, et al. Five-Day Preoperative Radiation Therapy for Patients With High-Risk Soft Tissue Sarcoma: A Nonrandomized Clinical Trial. JAMA Netw Open. 2025;8(12):e2550195. doi:10.1001/jamanetworkopen.2025.50195
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