Genetics and management of locally advanced carcinomas of the head and neck: role of altered fractionation radiotherapy

Lay abstract: Management of head and neck squamous cell carcinomas is very challenging, with malignancies often strongly dampening the quality of life of the patients. Surgery has gradually lost its importance and it is often replaced by combined chemoradiotherapy. Response to chemoradiotherapy is very variable and, at present, it is not possible to know which patients will benefit from it. Genetic assessment of head and neck squamous cell carcinomasmay help clinicians to perform a well-shaped therapy, adapted on the basis of the patient's genetic features. This strategy is presently experimental, but it may become the 'standard' in the future.

Squamous cell carcinoma of the head and neck (SCCHN) accounts for 5-7% of all malignancies. About 60% of newly diagnosed SCCHN are detected as locally advanced disease. Chemoradiation is a standard option and response rate to it is variable. Recently, a genetic classification of SCCHN has been proposed by Chung et al., who categorized all SCCHN into four subtypes. The basal-like variant is characterized by high expression of EGFR. Literature data suggest higher efficacy of accelerated and/or hyperfractionated radiotherapy, if compared with conventional radiotherapy in the subgroup of patients with high EGFR expression. In this review, we will describe the genetic factors able to guide treatment choice, with a focus on EGFR expression.