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High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy

OBJECTIVES: Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) ge...

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Autores principales: Bruine de Bruin, Leonie, Schuuring, Ed, de Bock, Geertruida H., Slagter‐Menkema, Lorian, Mastik, Mirjam F., Noordhuis, Maartje G., Langendijk, Johannes A., Kluin, Philip M., van der Laan, Bernard F.A.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384019/
https://www.ncbi.nlm.nih.gov/pubmed/32275333
http://dx.doi.org/10.1002/lary.28641
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author Bruine de Bruin, Leonie
Schuuring, Ed
de Bock, Geertruida H.
Slagter‐Menkema, Lorian
Mastik, Mirjam F.
Noordhuis, Maartje G.
Langendijk, Johannes A.
Kluin, Philip M.
van der Laan, Bernard F.A.M.
author_facet Bruine de Bruin, Leonie
Schuuring, Ed
de Bock, Geertruida H.
Slagter‐Menkema, Lorian
Mastik, Mirjam F.
Noordhuis, Maartje G.
Langendijk, Johannes A.
Kluin, Philip M.
van der Laan, Bernard F.A.M.
author_sort Bruine de Bruin, Leonie
collection PubMed
description OBJECTIVES: Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation. METHODS: The prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1‐T2 LSCC curatively treated with external beam radiotherapy. Uni‐ and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control. RESULTS: Local control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08–4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40–84.4; P = .02). CONCLUSION: Our findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 1954–1960, 2020
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spelling pubmed-73840192020-07-28 High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy Bruine de Bruin, Leonie Schuuring, Ed de Bock, Geertruida H. Slagter‐Menkema, Lorian Mastik, Mirjam F. Noordhuis, Maartje G. Langendijk, Johannes A. Kluin, Philip M. van der Laan, Bernard F.A.M. Laryngoscope Head and Neck OBJECTIVES: Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation. METHODS: The prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1‐T2 LSCC curatively treated with external beam radiotherapy. Uni‐ and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control. RESULTS: Local control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08–4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40–84.4; P = .02). CONCLUSION: Our findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 1954–1960, 2020 John Wiley & Sons, Inc. 2020-04-10 2020-08 /pmc/articles/PMC7384019/ /pubmed/32275333 http://dx.doi.org/10.1002/lary.28641 Text en © 2020 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on behalf of The American Laryngological, Rhinological and Otological Society, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Head and Neck
Bruine de Bruin, Leonie
Schuuring, Ed
de Bock, Geertruida H.
Slagter‐Menkema, Lorian
Mastik, Mirjam F.
Noordhuis, Maartje G.
Langendijk, Johannes A.
Kluin, Philip M.
van der Laan, Bernard F.A.M.
High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title_full High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title_fullStr High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title_full_unstemmed High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title_short High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy
title_sort high patm is associated with poor local control in supraglottic cancer treated with radiotherapy
topic Head and Neck
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384019/
https://www.ncbi.nlm.nih.gov/pubmed/32275333
http://dx.doi.org/10.1002/lary.28641
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