Phase II, national, multicentric, prospective, randomized (1:1) non-inferiority trial with two parallel groups, incorporating a concurrent observational cohort of eligible non-randomized patients, designed to address critical knowledge gaps by prospectively evaluating the safety, efficacy, and feasibility of preoperative ultra-hypofractionated radiotherapy (HFRT) in patients with soft tissue sarcomas (STS) of the extremities and trunk.
This study is designed to address critical knowledge gaps by prospectively evaluating the safety, efficacy, and feasibility of preoperative ultra-hypofractionated radiotherapy (HFRT) in patients with soft tissue sarcomas (STS) of the extremities and trunk. Eligible patients will be randomized to receive an ultra-hypofractionated RT regimen consisting of 30 Gy delivered in 5 fractions of 6 Gy, followed by surgical resection at one of two predefined intervals: either 1-2 weeks or 4-6 weeks after completion of radiotherapy. In parallel, a non-randomized observational cohort will be recorded, consisting of patients treated according to current standard practice - surgery alone or surgery preceded by nonventional RT (50 Gy in 25 fractions) - to provide a contemporaneous benchmark for comparison. The aim of this study is to gather high-quality clinical evidence on the impact of ultra-hypofractionated RT on oncologic outcomes, treatment-related toxicity, perioperative morbidity, and patient-reported quality of life. Evaluation of logistical and economic implications of treatment de-escalation, such as healthcare resource utilization and treatment burden are also an important point to be addressed. By systematically assessing these endpoints, this study aims to inform future clinical guidelines and support the potential integration of ultra-hypofractionated RT into routine clinical practice for selected patients with localized STS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 1-2 weeks after treatment
hypofractionated radiotherapy (30Gy/5 fractions) and surgical resection at 4-6 weeks after treatment
Determine the incidence of postoperative complications
The primary objective of this study is to determine the incidence of postoperative complications (according to Clavien-Dindo) within 90 days from surgery
Time frame: Day of surgery (DOS); 7-14-21-30-60-90 days post DOS; 4-8-12-16-20-24 months post DOS
Quality of Life (QoL)
Quality of Life (QoL)
Time frame: At last available QoL assessment date for patients without confirmed deterioration
Overall Survival (OS)
Overall Survival (OS)
Time frame: At the last date that patient was known to be alive
Disease-Free Survival (DFS)
Disease-Free Survival (DFS)
Time frame: Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Local Recurrence (CCI-LR)
Cumulative Incidence of Local Recurrence (CCI-LR)
Time frame: Months 4-8-12-16-20-24 post surgery
Cumulative Incidence of Distant Metastasis (CCI-DM)
Cumulative Incidence of Distant Metastasis (CCI-DM)
Time frame: Months 4-8-12-16-20-24 post surgery
Pathological response
Pathological response
Time frame: At any time during the study
Radiological response (RECIST 1.1 and CHOI)
Radiological response (RECIST 1.1 and CHOI)
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Time frame: Months 4-8-12-16-20-24 post surgery
Treatment-related toxicity
Treatment-related toxicity (based on Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0)
Time frame: 7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS
Postoperative complications
Postoperative complications (classified according to Clavien-Dindo and CCI)
Time frame: 7-14-21-30-60-90 days DOS, 4-8-12-16-20-24 months post DOS