Assessment of the Long-term Efficacy of Moderately Hypofractionated Neoadjuvant Radiotherapy Soft Tissue Sarcoma in the Limbs or Trunk Wall

Phase II Clinical Trial Assessing the Long-term Efficacy of Moderately Hypofractionated Neoadjuvant Radiotherapy Soft Tissue Sarcoma in the Limbs or Trunk Wall, Incorporating Translationnal Research

This trial aims to assess the long-term efficacy of moderately hypofractionated neoadjuvant radiotherapy for soft tissue sarcoma in the limbs or trunk wall. The primary outcome is local disease control, assessed by the cumulative incidence of progression/recurrence.

After informed consent has been obtained and eligibility criteria have been checked, a baseline assessment will be performed followed by the experimental treatment: intensity-modulated radiotherapy with a moderately hypofractionated regimen consisting in 15 fractions of 2.7 Gy administered over 3 weeks.

a follow-up assessment will be performed 3 to 4 weeks after the last radiotherapy session.

Tumor resection will be performed 4 to 8 weeks after the radiotherapy. Patients will then be followed up until the end of the study; planned 5 years after the last inclusion.

Radiotherapy will be evaluated in terms of safety and efficacy.

The NEORASARC clinical trial aims to assess the long-term efficacy of moderately hypofractionated neoadjuvant radiotherapy for soft tissue sarcoma in the limbs or trunk wall.

After informed consent has been obtained and eligibility criteria have been checked, a baseline assessment will be performed 8 weeks prior to the start of experimental treatment. This baseline assessment will consist in of a clinical examination, an MRI scan, and the completion of the MSTS and QLQ-C30 questionnaires. After a blood sample has been taken for translational research, the patient will receive the experimental treatment : intensity-modulated radiotherapy delivered in a moderately hypofractionated scheme consisting in 15 fractions of 2.7 Gy over 3 weeks. The total prescribed dose will be 40.5 Gy.

3 to 4 weeks after the last radiotherapy session, patients will undergo an MRI scan.

Tumor resection will be performed 4 to 8 weeks after the radiotherapy. A blood sample will be taken prior to this surgery for translational research.

Patients will then be followed up every 4 months for the first 2 years, every 6 months for 3 years and then annually until the end of the study. At each follow up, a clinical examination, an MRI scan and the completion of the MSTS and QLQ-C30/F17 questionnaires will be performed.

The study is planned to end 5 years after the last inclusion. The security and efficacy of the experimental treatment will be assessed. The main analysis will focus on the cumulative incidence of local progressive disease or recurrence at the two-year follow-up.

It is expected that 90% of patients are free of local progression or recurrence at two years in this population and with different radiotherapy regimen. A proportion of patients free from local progression or recurrence at two years of 90% or less will be considered insufficient (p0 = 90%). The alternative hypothesis under consideration is p1 = 95%.

Inclusion Criteria:

• Patient aged ≥ 18 years ;
• Localised sarcoma of a limb, the root of a limb, or the trunk wall ;
• Histologically confirmed diagnosis of soft tissue sarcoma regardless of the grade ;
• Diagnosis biopsy performed at Centre Oscar Lambret, with specimen available for translational research ;
• Indication of neoadjuvant radiotherapy according to the multidisciplinary consultation meeting ;
• Tumor considered operable with a curative intent and conservative intent according to the multidisciplinary consultation meeting ;
• Affiliation to the French National Social Security System ;
• Informed and signed consent

Exclusion Criteria:

• Metastatic disease (including local lymph node diffusion) ;
• Visceral or retroperitoneal sarcoma ;
• Tumor considered inoperable even after radiotherapy, according to the multidisciplinary consultation meeting ;
• Indication of neoadjuvant or adjuvant chemotherapy ;
• Ewing tumor of soft tissue, desmoid tumor, embryonal or alveolar rhabdomyosarcoma ;
• Pregnant or breastfeeding women ;
• Patients under protective measures ;
• Patient refusal.