Radiation Biology

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SU_40_2400 - Fast, reliable and cost-effective assay on lymphocytes to predict radiosensitivity: development on prostate and head and neck cohort

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Fast, reliable and cost-effective assay on lymphocytes to predict radiosensitivity: development on prostate and head and neck cohort
S. Deneuve1, C. Mirjolet2, M. Duclos3, A. Rehailia Blanchard4,5, P. Retif6, N. Foray7, T. Bastogne8, and S. Pereira9; 1Centre Leon Berard, Lyon, France, 2CGFL DIJON, DIJON, France, 3neolys diagnostics, Lyon, France, 4Lucien Neuwirth Cancer Institute, SAint Priest en Jarez, France, 5Institut de Cancérologie Lucien Neuwirth, Saint-Priest en Jarez, France, 6centre hospitalier regional, metz, France, 7CRCL lyon, lyon, France, 8cybernano, villers les nancy, France, 9Neolys Diagnostics, LYON CEDEX 08, France

Purpose/Objective(s): The challenge of optimizing patient care around radiation therapy is constantly tackled with a flow of innovations such as Robot assisted surgery, Protons or Spacer. Various studies have demonstrated the efficacy of new techniques, however very few discriminate patients on their likelihood to exhibit side effects. Radiosensitivity tests could be key elements in decision making in various situations: radiation therapy versus surgery, hypo versus normofractionnated radiotherapy, proton versus photontherapy, and spacers implementation. Recent studies based on immunofluorescence experiments on skin fibroblasts have stressed the role of the ATM protein (pATM), and the statistical reliability of this molecular endpoint to predict individual radiosensitivity (Granzotto et al, 2016). Faster and simpler solutions based on ELISA assays on fibroblasts (EF) have confirmed that the pATM is a relevant biomarker (Pereira et al, IJROBP 2018). The purpose of this study was to develop a predictive assay on lymphocytes based on the quantification of the pATM using the ELISA method.

Materials/Methods: A blind retrospective study was performed on 102 blood lymphocytes collected from 56 radioresistant (RR) and 46 radiosensitive (RS) patients, presenting with either a prostate or head and neck cancer. To begin with, all patients were divided in 2 groups, RR (CTCAE<2) and RS (CTCAE≥2). The global quantity of pATM molecules was assessed using the ELISA method. Then, a classification study was carried out to estimate the threshold value of the biomarker in order to minimize the number of false positives (RS patients identified RR). A Support Vector Machine classification technique was used to predict the radio-sensitivity, and a cross-validation study based on a Bootstrap method was applied. Statistical analysis was developed on R and performed independently.

Results: After promising results obtained with IF (AUC = 0.97) and EF (AUC = 0.83), the experiments performed on lymphocytes showed that the quantities of pATM molecules found in each sample were consistent with the CTCAE grades. Statistical results showed the following mean values regarding classification performances for all patients: sensitivity=86 %, specificity=72 %, AUC=79%, NPV=84 % and PPV=74 %.

Conclusion: This study performed using a single blood sample, confirmed results obtained with previous other methods,while providing a realistic, cost effective assay that could be potentially proposed to every patient that could undergo radiation therapy.

Author Disclosure: S. Deneuve: None. C. Mirjolet: None. M. Duclos: None. A. Rehailia Blanchard: None. P. Retif: None. N. Foray: Partner; Neolys Diagnostics.

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SU_40_2400 - Fast, reliable and cost-effective assay on lymphocytes to predict radiosensitivity: development on prostate and head and neck cohort



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