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

Recruiting

• Conditions: Soft Tissue Sarcomas
• Interventions: Radiation: pre-operative radiation; Procedure: Standard surgery after rpreoprative radiation

• Registration Number: NCT05739084
• Lead Sponsor: Centre Leon Berard

Brief Summary

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

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 Timeline

• Study Start: 2022-11-23
• Study First Submitted: 2023-01-26
• Status Verified: 2023-02
• Study First Submitted QC: 2023-02-20
• Last Update Submitted: 2023-02-20
• Study First Posted: 2023-02-22
• Last Update Posted: 2023-02-22
• Primary Completion: 2025-06-23
• Study Completion: 2025-11-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Prospective cohort	pre-operative radiation	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.
Retrospective cohort	pre-operative radiation	A total sample size of 200 patients is expected in the retrospective thanks to the NETSARC/ CONTICABASE databases (French sarcoma reference network)
Retrospective cohort	Standard surgery after rpreoprative radiation	A total sample size of 200 patients is expected in the retrospective thanks to the NETSARC/ CONTICABASE databases (French sarcoma reference network)
Prospective cohort	Standard surgery after rpreoprative radiation	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.

Primary Outcome Measures

Name	Time	Method
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	36 months	Gene expression signature using RNAseq correlated to the percentage of residual viable cells on surgery specimen to define histological response.

Secondary Outcome Measures

Name	Time	Method
To identify biomarkers of sensitivity or resistance to radiotherapy in STS patients using additional clinical endpoints	36 months	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.

Trial Locations

Locations (1)

Centre Léon Bérard; 🇫🇷 Lyon, France