Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity
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 an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/10/2477 |
| _version_ | 1797533486066696192 |
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| author | Sophie Deneuve Céline Mirjolet Thierry Bastogne Mirlande Duclos Paul Retif Philippe Zrounba Pierre-Eric Roux Marc Poupart Guillaume Vogin Nicolas Foray Sandrine Pereira |
| author_facet | Sophie Deneuve Céline Mirjolet Thierry Bastogne Mirlande Duclos Paul Retif Philippe Zrounba Pierre-Eric Roux Marc Poupart Guillaume Vogin Nicolas Foray Sandrine Pereira |
| author_sort | Sophie Deneuve |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:15:13Z |
| format | Article |
| id | doaj.art-731bdc000cf348c3b4b5eafb316f5709 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:15:13Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-731bdc000cf348c3b4b5eafb316f57092023-11-21T20:28:06ZengMDPI AGCancers2072-66942021-05-011310247710.3390/cancers13102477Proof of Concept of a Binary Blood Assay for Predicting RadiosensitivitySophie Deneuve0Céline Mirjolet1Thierry Bastogne2Mirlande Duclos3Paul Retif4Philippe Zrounba5Pierre-Eric Roux6Marc Poupart7Guillaume Vogin8Nicolas Foray9Sandrine Pereira10Centre Léon Bérard, UNICANCER, 69008 Lyon, FranceCentre Georges François Leclerc, UNICANCER, 27877 Dijon, FranceCRAN CNRS UMR 7039, Université de Lorraine, 54505 Vandœuvre-lès-Nancy, FranceNeolys Diagnostics, 67960 Strasbourg, FranceRadiation Therapy Department, Centre Hospitalier Régional Metz-Thionville, 57530 Ars-Laquenexy, FranceCentre Léon Bérard, UNICANCER, 69008 Lyon, FranceCentre Léon Bérard, UNICANCER, 69008 Lyon, FranceCentre Léon Bérard, UNICANCER, 69008 Lyon, FranceCentre François Baclesse, 4240 Ezch-sur-Alzette, LuxembourgRadiobiology Group, U1296 INSERM, 69008 Lyon, FranceRadiobiology Group, U1296 INSERM, 69008 Lyon, FranceRadiation 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.https://www.mdpi.com/2072-6694/13/10/2477cancerradiation-induced toxicity predictionbiological markerpATMnormal tissue complication probability |
| spellingShingle | Sophie Deneuve Céline Mirjolet Thierry Bastogne Mirlande Duclos Paul Retif Philippe Zrounba Pierre-Eric Roux Marc Poupart Guillaume Vogin Nicolas Foray Sandrine Pereira Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity Cancers cancer radiation-induced toxicity prediction biological marker pATM normal tissue complication probability |
| title | Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity |
| title_full | Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity |
| title_fullStr | Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity |
| title_full_unstemmed | Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity |
| title_short | Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity |
| title_sort | proof of concept of a binary blood assay for predicting radiosensitivity |
| topic | cancer radiation-induced toxicity prediction biological marker pATM normal tissue complication probability |
| url | https://www.mdpi.com/2072-6694/13/10/2477 |
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