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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Soft Tissue Sarcomas

Intervention / Treatment
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* Radiation: pre-operative radiation
* Procedure: Standard surgery after rpreoprative radiation


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective cohort<br>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<br>* As per standard of care and institutional guidelines<br>Procedure: Standard surgery after rpreoprative radiation<br>* As per standard of care and institutional guidelines<br>|
| Prospective cohort<br>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<br>* As per standard of care and institutional guidelines<br>Procedure: Standard surgery after rpreoprative radiation<br>* As per standard of care and institutional guidelines<br>|

What is the study measuring?
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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 |