Methods to overcome radiation resistance in head and neck cancer
- Bruce E Brockstein, MD
Bruce E Brockstein, MD
- Section Editor — Cancer of the Head and Neck
- Clinical Professor of Medicine
- University of Chicago Pritzker School of Medicine
- Everett E Vokes, MD
Everett E Vokes, MD
- John E. Ultmann Professor
- Chairman, Department of Medicine
- Physician-in-Chief, University of Chicago Medicine and Biologic Sciences
- David S Yoo, MD, PhD
David S Yoo, MD, PhD
- Medical Instructor
- Department of Radiation Oncology
- Duke University Medical Center
- Section Editors
- Marshall R Posner, MD
Marshall R Posner, MD
- Section Editor — Cancer of the Head and Neck
- Professor of Gene and Cell Medicine
- The Tisch Cancer Institute
- Icahn School of Medicine at Mount Sinai
- David M Brizel, MD
David M Brizel, MD
- Section Editor — Radiation Therapy
- Leonard R Prosnitz Professor of Radiation Oncology
- Professor of Otolaryngology Head & Neck Surgery
- Duke University Cancer Institute
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 . Radioresistance is a broad term that describes the relative resistance of individual cells, tissues, organs, or entire organisms to the biologic effects of RT .
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 alone for advanced (stage III and IV) head and neck cancer: Dose and fractionation schedule".)
MECHANISMS OF RADIORESISTANCE
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), the patient (human papillomavirus status, hemoglobin levels, smoking status), and biologic factors (hypoxia, proliferation status, expression of deoxyribonucleic acid [DNA] repair 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-International Union for Cancer Control (AJCC-UICC) tumor node metastasis (TNM) staging system for the different primary sites . 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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- MECHANISMS OF RADIORESISTANCE
- Clinical factors affecting radiation response
- - Primary tumor characteristics
- - Inherent tumor cell radioresistance
- Patient factors
- - Hemoglobin
- - Smoking status
- Biological factors determining radiation response
- - Hypoxia
- - Repopulation
- - Inherent tumor cell radioresistance
- - Cancer stem cells
- - Other factors
- STRATEGIES TO OVERCOME RADIORESISTANCE
- Altered fractionation RT
- Concurrent systemic therapy
- - Chemotherapy
- - Molecularly targeted agents
- OTHER APPROACHES
- Targeting hypoxia
- - Hypoxic cell sensitizers
- - Hypoxic cell cytotoxins
- - Hyperbaric oxygen
- - Functional imaging
- Correction of anemia
- - Transfusion
- - Erythropoiesis-stimulating agents