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Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features
Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reaction...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779824/ https://www.ncbi.nlm.nih.gov/pubmed/31632918 http://dx.doi.org/10.3389/fonc.2019.00987 |
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author | Palumbo, Elisa Piotto, Celeste Calura, Enrica Fasanaro, Elena Groff, Elena Busato, Fabio El Khouzai, Badr Rigo, Michele Baggio, Laura Romualdi, Chiara Zafiropoulos, Demetre Russo, Antonella Mognato, Maddalena Corti, Luigi |
author_facet | Palumbo, Elisa Piotto, Celeste Calura, Enrica Fasanaro, Elena Groff, Elena Busato, Fabio El Khouzai, Badr Rigo, Michele Baggio, Laura Romualdi, Chiara Zafiropoulos, Demetre Russo, Antonella Mognato, Maddalena Corti, Luigi |
author_sort | Palumbo, Elisa |
collection | PubMed |
description | Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity. Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G(2)-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes. Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX). Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues. |
format | Online Article Text |
id | pubmed-6779824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67798242019-10-18 Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features Palumbo, Elisa Piotto, Celeste Calura, Enrica Fasanaro, Elena Groff, Elena Busato, Fabio El Khouzai, Badr Rigo, Michele Baggio, Laura Romualdi, Chiara Zafiropoulos, Demetre Russo, Antonella Mognato, Maddalena Corti, Luigi Front Oncol Oncology Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity. Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G(2)-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes. Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX). Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues. Frontiers Media S.A. 2019-10-01 /pmc/articles/PMC6779824/ /pubmed/31632918 http://dx.doi.org/10.3389/fonc.2019.00987 Text en Copyright © 2019 Palumbo, Piotto, Calura, Fasanaro, Groff, Busato, El Khouzai, Rigo, Baggio, Romualdi, Zafiropoulos, Russo, Mognato and Corti. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Palumbo, Elisa Piotto, Celeste Calura, Enrica Fasanaro, Elena Groff, Elena Busato, Fabio El Khouzai, Badr Rigo, Michele Baggio, Laura Romualdi, Chiara Zafiropoulos, Demetre Russo, Antonella Mognato, Maddalena Corti, Luigi Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title | Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title_full | Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title_fullStr | Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title_full_unstemmed | Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title_short | Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features |
title_sort | individual radiosensitivity in oncological patients: linking adverse normal tissue reactions and genetic features |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779824/ https://www.ncbi.nlm.nih.gov/pubmed/31632918 http://dx.doi.org/10.3389/fonc.2019.00987 |
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