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Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity

Centre Léon Bérard, UNICANCER, 69008 Lyon, France
Radiobiology Group, U1296 INSERM, 69008 Lyon, France
Centre Georges François Leclerc, UNICANCER, 27877 Dijon, France
INSERM UMR 1231, Cadir Team, Faculté de Médecine, 27877 Dijon, France
CRAN CNRS UMR 7039, Université de Lorraine, 54505 Vandœuvre-lès-Nancy, France
INRIA BIGS, Université de Lorraine, 54505 Vandœuvre-lès-Nancy, France
CYBERnano, Université de Lorraine, 54505 Vandœuvre-lès-Nancy, France
Neolys Diagnostics, 67960 Strasbourg, France
Radiation Therapy Department, Centre Hospitalier Régional Metz-Thionville, 57530 Ars-Laquenexy, France
Centre François Baclesse, 4240 Ezch-sur-Alzette, Luxembourg
UMR 7365 CNRS-UL IMOPA, Équipe 1, Faculté de Médecine, 54505 Vandœuvre-lès-Nancy, France
Author to whom correspondence should be addressed.
These authors contribute equally to the work.
Academic Editor: Laure Marignol
Cancers 2021, 13(10), 2477;
Received: 29 March 2021 / Revised: 12 May 2021 / Accepted: 13 May 2021 / Published: 19 May 2021
(This article belongs to the Special Issue The Rs, Fractionation and the Radiation Response)
Early toxicity of radiotherapy (RT) (from the beginning of treatment to 3 months after its end) may compromise cancer treatments and its prediction is a medical, social and economic challenge. Beyond clinical/dosimetric factors, much of the variation in the risk of toxicity is currently unexplained and largely attributed to individual radiosensitivity (IRS). Thus, radiosensitivity tests would help several decision makings for choosing fractionation, preferring surgery to radiation or proton to photons for instance. Numerous initiatives failed in implementing predictive assays of IRS in clinical routine. Here we assess and validate the predictive ability of a new assay RADIODTECT® (RDT), based on phosphorylated ATM protein quantification in lymphocytes, for early toxicity after radiotherapy (RT). This study demonstrated promising results and implementing RTD as an easy managing test in common RT clinical practice for patients can be advisable.
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. View Full-Text
Keywords: cancer; radiation-induced toxicity prediction; biological marker; pATM; normal tissue complication probability cancer; radiation-induced toxicity prediction; biological marker; pATM; normal tissue complication probability
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MDPI and ACS Style

Deneuve, S.; Mirjolet, C.; Bastogne, T.; Duclos, M.; Retif, P.; Zrounba, P.; Roux, P.-E.; Poupart, M.; Vogin, G.; Foray, N.; Pereira, S. Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity. Cancers 2021, 13, 2477.

AMA Style

Deneuve S, Mirjolet C, Bastogne T, Duclos M, Retif P, Zrounba P, Roux P-E, Poupart M, Vogin G, Foray N, Pereira S. Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity. Cancers. 2021; 13(10):2477.

Chicago/Turabian Style

Deneuve, Sophie, Céline Mirjolet, Thierry Bastogne, Mirlande Duclos, Paul Retif, Philippe Zrounba, Pierre-Eric Roux, Marc Poupart, Guillaume Vogin, Nicolas Foray, and Sandrine Pereira. 2021. "Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity" Cancers 13, no. 10: 2477.

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