HighpATMis Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy

Leonie Bruine de Bruin, Ed Schuuring*, Geertruida H de Bock, Lorian Slagter-Menkema, Mirjam F Mastik, Maartje G Noordhuis, Johannes A Langendijk, Philip M Kluin, Bernard F A M van der Laan

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)1954-1960
Number of pages7
JournalLaryngoscope
Volume130
Issue number8
Early online date10-Apr-2020
DOIs
Publication statusPublished - 1-Aug-2020

Keywords

  • Laryngeal squamous cell carcinoma
  • radiotherapy
  • local control
  • ataxia telangiectasia mutated (ATM)
  • SQUAMOUS-CELL CARCINOMA
  • ATAXIA-TELANGIECTASIA
  • LARYNGEAL CARCINOMA
  • PROGNOSTIC-SIGNIFICANCE
  • IONIZING-RADIATION
  • GLOTTIC CARCINOMA
  • DOSE-ESCALATION
  • UNITED-STATES
  • NECK-CANCER
  • PHASE-I

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