Predictive Study of Radiation Induced Sarcoma From the GSF-GETO Data Base.
The biological study will include the two following steps:1. On frozen specimen: genic
profile of the tumor will be studied with two different techniques: CGH-array from extracted
DNA in order to evaluate the number of gene copies, amplifications and deletions. The RNAm
expression profile will be studied to evaluate the level of the gene expression. More than
200 data collected in Institut Bergonié, coming from de novo sarcoma would be used as a
comparative specimen since the pathological diagnosis is the same as the one observed for
radiation induced sarcoma. A comparison between the two populations will be able to define
profiles, gene modifications and signalisation pathways of radiation induced sarcoma. 2. On
blood sample: 2 groups of patients will be compared: those with radiation induced sarcoma
and patients receiving radiation therapy for more than 5 years ago without developing
sarcoma. The study will be performed with the inform consent of the patients and of the
controlled cases.This second step requires 2 blood samples (2 x 5 ml). They will be
collected and sent to the molecular biology laboratory located in Centre Alexis VAUTRIN
(Nancy).- One sample of 5 mm will be dedicated to study radiation induced apoptosis assessed
by flow cytometry. A correlation has been described between radiation-induced apoptosis of
CT8+ lymphocytes after an 8 Gy irradiation and the occurrence of severe late toxicity after
radiation therapy for patients treated for several types of tumors.- The second sample will
be used to study the polymorphism of the genes involved in reparation of DNA by using chip
screening of single nucleotide polymorphisms (SNP). This sample will be used after DNA
extraction from mononuclear blood cells. DNA will be extracted and controlled by flow
cytometrical separation. It will be sent to Bordeaux molecular biology laboratory in
Institut Bergonié (Prof. JM COINDRE) to perform an evaluation of the single nucleotide
polymorphism. The aim of this part of the protocol is to study variances in gene, the
product of which plays a role in radiation response and in the development of adverse
effects after radiation therapy. For patients with radiation-induced sarcoma, the results
of this analysis will be compared with the data obtained from DNA analysis extracted from
the tumors. The clinical, pathological and biological characterisation of radiation-induced
sarcoma obtained will allow to identify constitutional variances linked with an increased
sensitivity to radiation therapy leading to discuss indication of irradiation in a
population at risk. Pediatric radiation therapy and adjuvant treatment after surgery for
breast carcinoma will be the main targets of this selection of patients. This project will
be able to select radiation modality in patients at risk (intensity modulated radiation
therapy or 3D conformal approach, stereotactic approaches, partial irradiation of the
breast).
radiation-induced sarcoma group
Interventional
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Determine the predictive clinical and biological risk factors to develop a sarcoma on irradiated territory.
Clinical data of initial radiation therapy, radiation-induced apoptosis of CT8+ lymphocytes and polymorphism of the genes involved in reparation of DNA by using chip screening of single nucleotide polymorphisms (SNP) will be studied for each patient included.
from date of inclusion up to the end of recruiting period : november 2013 (anticipated)
No
Phillipe Maingon, Professor
Principal Investigator
Centre Georges Francois Leclerc
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
0328-3maph11
NCT01504360
December 2011
December 2013
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