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Methods to overcome radiation resistance in head and neck cancer

Bruce E Brockstein, MD
Everett E Vokes, MD
David S Yoo, MD, PhD
Section Editors
Marshall R Posner, MD
David M Brizel, MD
Deputy Editor
Michael E Ross, MD


Radiation therapy (RT) plays a major role in the management of head and neck squamous cell carcinomas. Despite therapeutic and technological advances, some patients will have persistence of irradiated tumor or develop locoregional failure, resulting in significant morbidity and mortality [1]. Radioresistance is a broad term that describes the relative resistance of individual cells, tissues, organs, or entire organisms to the biologic effects of RT [2].

Mechanisms of radioresistance to RT in head and neck cancer and strategies used to overcome this resistance are discussed here. Concurrent chemoradiotherapy is discussed in detail separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy" and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations".)


Many factors affect the responsiveness of tumors to radiation therapy (RT). Individual patients with tumors of similar size and stage can respond very differently to RT.

Relevant factors are related to the primary tumor (volume, size, grade, human papillomavirus [HPV] status), the patient (hemoglobin levels, smoking status), and biologic factors (hypoxia, proliferation status, expression of DNA repair genes, and alterations of many other genes).

Clinical factors affecting radiation response

Primary tumor characteristics — The complexity and variability of clinical outcomes in head and neck cancer are reflected in the spectrum of T stage descriptors used in the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) staging system for the different primary sites [3]. Larger tumors and/or those with more extensive local invasion have higher T classifications, corresponding to a likely higher malignant cell burden and poorer prognosis. (See "Overview of the diagnosis and staging of head and neck cancer".)

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Literature review current through: Nov 2017. | This topic last updated: Nov 09, 2017.
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