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. 2021 May 19;13(10):2477.
doi: 10.3390/cancers13102477.

Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity

Sophie Deneuve  1   2 , Céline Mirjolet  3   4 , Thierry Bastogne  5   6   7 , Mirlande Duclos  8 , Paul Retif  9 , Philippe Zrounba  1 , Pierre-Eric Roux  1 , Marc Poupart  1 , Guillaume Vogin  10   11 , Nicolas Foray  2 , Sandrine Pereira  2   8
Affiliations

Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity

Sophie Deneuve et al. Cancers (Basel). .

Abstract

Radiation therapy (RT), either alone or in combination with surgery and/or chemotherapy is a keystone of cancers treatment. Early toxicity is common, sometimes leading to discontinuation of treatment. Recent studies stressed the role of the phosphorylated ATM (pATM) protein in RT-toxicity genesis and its ability in predicting individual radiosensitivity (IRS) in fibroblasts. Here we assessed the reliability of the pATM quantification in lymphocytes to predict IRS. A first retrospective study was performed on 150 blood lymphocytes of patients with several cancer types. Patients were divided into 2 groups, according to the grade of experienced toxicity. The global quantity of pATM molecules was assessed by ELISA on lymphocytes to determine the best threshold value. Then, the binary assay was assessed on a validation cohort of 36 patients with head and neck cancers. The quantity of pATM molecules in each sample of the training cohort was found in agreement with the observed Common Terminology Criteria for Adverse Events (CTCAE) grades with an AUC = 0.71 alone and of 0.77 combined to chemotherapy information. In the validation cohort, the same test was conducted with the following performances: sensitivity = 0.84, specificity = 0.54, AUC = 0.70 and 0.72 combined to chemotherapy. This study provides the basis of an easy to perform assay for clinical use.

Keywords: biological marker; cancer; normal tissue complication probability; pATM; radiation-induced toxicity prediction.

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Conflict of interest statement

T.B. is co-founder and scientific expert in biostatistics and nano-informatics in CYBERNANO Company (Biosignal Processing & Biostatistics). T.B. was employed by the company Cybernano. N.F. and S.P. reports the following patents: FR3040178A1, FR3040179A1, WO2017098190A1, EP3685163A1. S.P. and M.D. are employed by the company Neolys diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Determination of the optimized threshold and prediction results of the 150 patients. (a) pATM ELISA assay distribution (pATM quantities are in ng/mL). (b) ROC analysis was performed on pATM ELISA results and a Wilcoxon rank sum test was also applied to compare RR and RS groups (p < 0.001). (c) Histogram of threshold frequencies after the bootstrap analysis.
Figure 2
Figure 2
Prediction results and performances of the RadioDtect® assay of the 36 HNSCC patients. (a) ROC analysis was performed on pATM ELISA results and a Wilcoxon rank sum test was also applied to compare RR and RS groups (p = 0.02). (b) Confusion matrix results for the prediction from the pATM data.
Figure 3
Figure 3
Performance analysis of combination of RadioDtect and chemotherapy as a binary variable for predicting grade ≥ 2 toxicities (A) ROC analysis for the testing cohort (B) ROC analysis for the validation cohort.
See this image and copyright information in PMC

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