Gene Signatures Searching of Sensitivity/Resistance to Neoadjuvant Radiotherapy in Patients With Resectable STS (RADIOSARC)

[RADIOSARC] Searching for Specific Gene Signature(s) of Sensitivity/Resistance to Neoadjuvant Radiotherapy in Adults Patients With Resectable Soft Tissue Sarcomas of Limbs

To date, the radiation oncologist are missing biomarkers predictive of response/resistance to RT in order to identify patients who may benefit from RT and personalize the RT schedule. Our proposal is to conduct a cohort study aiming at identifying transcriptomic biomarkers predictive of sensitivity and/or resistance to RT in limbs STS patients

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcomas
• Intervention / Treatment: Radiation: pre-operative radiation; Procedure: Standard surgery after rpreoprative radiation

Detailed Description

Whether RT should be performed pre or post-operatively is still a debated question. To date, the radiation oncologist are missing signature of response/resistance to RT in order to identify patients who may benefit from RT and personalize the RT schedule. Therefore, predicting the likelihood of response/resistance to RT is essential. The individual exploration with high-throughput approaches will participate in describing biological mechanisms involved in STS tumor cell pan-resistance, thus identifying potential molecular targets that could be inhibited to reverse intrinsic radioresistance. In this context, our proposal is to conduct a cohort study aiming at identifying transcriptomic signature predictive of sensitivity and/or resistance to RT in limbs STS patients.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Marie -Pierre SUNYACH, MD; Phone Number: +33(0)4 78 78 28 28; Email: MariePierre.SUNYACH@lyon.unicancer.fr
• Study Contact Backup: Name: Waisse Waissi, MD; Phone Number: +33(0)4 78 78 28 28; Email: Waisse.WAISSI@lyon.unicancer.fr

Study Locations

• France
  • Lyon, France
    • Recruiting
    • Centre Leon Berard
    • Contact: Marie-Pierre SUNYACH, MD; Phone Number: +33 (0)4 78 78 28 28; Email: MariePierre.SUNYACH@lyon.unicancer.fr
    • Contact: Waisse Waissi, MD; Phone Number: +33 (0)4 78 78 28 28; Email: Waisse.WAISSI@lyon.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Soft tissus sarcoma who underwent/undergo to preoperative Radiation and for whom resected tumour specimen is available.

Description

Inclusion Criteria:

• Male and female ≥ 18 years at time of non-opposition to participate to the study
• Patient with documented non-opposition to participate to the study.
• Patient with histologically and cytologically confirmed diagnosis with STS (..)
• Patient with availability of FFPE tumor block from initial diagnosis biopsy (mandatory) and surgery specimen (optional).
• Patients with tumor FFPE samples prepared with the last 4 years
• Patient with evaluable tumor sample meeting the following quality/quantity control criteria (..)

Exclusion Criteria:

• Patients with metastatic soft tissue sarcoma at diagnosis
• Patients with exclusive radiotherapy without surgical resection
• Patients receiving neo adjuvant systemic treatment (chemotherapy, immunotherapy, targeted therapy)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective cohort; A total sample size of 200 patients is expected in the retrospective thanks to the NETSARC/ CONTICABASE databases (French sarcoma reference network)	Radiation: pre-operative radiation; As per standard of care and institutional guidelines; Procedure: Standard surgery after rpreoprative radiation; As per standard of care and institutional guidelines
Prospective cohort; To ensure an external validation, patients from NETsarc centers experiencing preoperative RT will be prospectively accrued and transcriptomic signature will be tested. Up to 100 patients will be enrolled in this prospective cohort.	Radiation: pre-operative radiation; As per standard of care and institutional guidelines; Procedure: Standard surgery after rpreoprative radiation; As per standard of care and institutional guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define a transcriptomic signature of histological response to radiotherapy in STS patients using the percentage of residual viable cells as a clinical meaningful endpoint	Gene expression signature using RNAseq correlated to the percentage of residual viable cells on surgery specimen to define histological response.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify biomarkers of sensitivity or resistance to radiotherapy in STS patients using additional clinical endpoints	Gene expression signature using RNAseq correlated to the percentage of necrosis, the percentage of fibrosis, the local control at 1 and 2 years (1- and 2-year local / distant recurrence-free survival, the time To Relapse (TTR), the Disease Free Survival (DFS), The Quality of resection level based on the residual tumor (R) classification.	36 months

Collaborators and Investigators

• Sponsor: Centre Leon Berard

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2022
• Primary Completion (Anticipated): June 23, 2025
• Study Completion (Anticipated): November 23, 2025

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Estimate): February 22, 2023

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: ET21-240 [RADIOSARC]; GDPR registration Number (Other Identifier: R201-004-171)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No