Short-course radiotherapy before surgery for soft tissue sarcoma

Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas; a Second Randomized Phase II Clinical Trial

This study tests whether a shorter course of radiation given before surgery (a 14 x 3 Gy schedule or an even shorter regimen) works as well and is safe for adults with intermediate- to high-grade soft tissue sarcoma.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 6 sites (Amsterdam and 5 other locations)
• Trial ID: NCT07071727 on ClinicalTrials.gov

What this trial studies

Adults with localized intermediate- to high-grade soft tissue sarcoma who are planned for combined radiotherapy and surgery are randomized to receive either a modestly hypofractionated preoperative schedule (14 x 3 Gy) or an even shorter preoperative regimen. The trial builds on prior phase II data, preliminary SCOPES results, and COVID-era treatment experience suggesting comparable toxicity and efficacy to conventional fractionation. Key entry requirements include tumor depth/size or grade criteria, no regional or distant metastases, and fitness for radiotherapy and definitive surgery. Participants will be followed for surgical outcomes, toxicity, patient-reported quality of life, and resource use.

Who should consider this trial

Good fit: Adults (≥18) with localized intermediate- to high-grade soft tissue sarcoma (deep and/or ≥5 cm and/or anticipated close margins and/or FNCLCC grade II/III), no regional/distant disease, WHO performance status ≤2, and who are able to undergo preoperative radiotherapy and surgery are ideal candidates.

Not a fit: Patients with metastatic disease, those who cannot undergo surgery or radiotherapy, or those with small low-grade superficial sarcomas that typically do not require preoperative radiotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, patients may receive effective preoperative radiation in fewer visits with similar cancer control and side effects, making treatment more convenient and easier on radiotherapy resources.

How similar studies have performed: Earlier phase II data and preliminary SCOPES/COVID-era experience suggest modest hypofractionation (14 x 3 Gy) and even ultra-hypofractionation (e.g., 5 x 6 Gy) can be safe and effective, but randomized evidence is limited.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed intermediate to high grade soft tissue sarcoma localized to the head and neck area, to the trunk and chest wall or to the extremities, for which the standard treatment is a combination of and radiotherapy and surgery (deep seated and/or ≥ 5cm in largest tumor diameter and/or an anticipated close resection margin and/or grade II/III according to the FNCLCC definition);
* Absence of regional and/or distant disease. Patients must be staged by at least a CT scan of the chest. Staging may also be performed by FDG-PET scanning and/or total body MRI scans;
* WHO Performance Status ≤ 2;
* Able and willing to undergo preoperative radiotherapy;
* Able and willing to undergo definitive surgery;
* Able and willing to comply with regular follow-up visits;
* Able and willing to complete patient reported outcome questionnaires (health-related quality of life and cost effectiveness);
* Able and willing to undergo randomization;
* Age ≥ 18 years;
* Signed written informed consent.

Exclusion Criteria:

* Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma;
* Patients with locally recurrent sarcomas, regardless of the management of the first sarcoma diagnosis;
* Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas;
* Myxoid liposarcomas, because they have shown to be exquisitely sensitive to a lower dose of radiation as compared to the 2 regimens tested in this trial.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
* Female patients who are pregnant;
* Intention to perform an isolated limb perfusion, instead of a tumor resection;
* Neoadjuvant chemotherapy both before and after radiotherapy.

Where this trial is running

Amsterdam and 5 other locations

• Netherlands Cancer Institute — Amsterdam, Netherlands (Not_yet_recruiting)
• Aumc — Amsterdam, Netherlands (Recruiting)
• Umcg — Groningen, Netherlands (Not_yet_recruiting)
• Lumc — Leiden, Netherlands (Not_yet_recruiting)
• Maastro — Maastricht, Netherlands (Recruiting)
• RadboudUMC — Nijmegen, Netherlands (Not_yet_recruiting)

Study contacts

• Study coordinator: Lisette M Wiltink, MD, PhD

Conditions Sarcoma of Soft Tissue; Sarcoma; Sarcoma, Soft Tissue; preoperative radiotherapy; radiotherapy