Challenges of integrating chemotherapy and targeted therapy with radiation in locally advanced head and neck squamous cell cancer

The curative treatment of locally advanced head and neck squamous cell cancer has advanced greatly in recent years, with the establishment of standard of care indications for chemoradiation (CRT). At the same time, there have been advances in each modality, including intensity-modulated radiation therapy, sequential chemotherapy and more tailored combination therapies. However, with new therapies come new challenges. This review will discuss some of the novel approaches to treating head and neck squamous cell cancer, particularly the introduction of biological agents into treatment paradigms, and some of the challenges arising as the field advances.A number of recent clinical trials have focused on reducing the disadvantages of concurrent CRT, specifically acute toxicity, lack of compliance and potential for late effects affecting quality of life and function. In particular, the use of biological agents as radiosensitizers has led to the investigation of new combination therapies, such as epidermal growth factor receptor inhibitors administered concurrently with CRT. These new therapies have potential for improving overall survival and lowering locoregional recurrence rates.Combination therapies hold promise for improving outcomes of patients with head and neck squamous cell cancer, both human papilloma virus-associated and human papilloma virus-negative tumors. The introduction of intensity modulated radiation therapy and biological agents into CRT treatment approaches may reduce some of the disadvantages of more traditional radiation and CRT treatments. Although many challenges remain, the possibility of improving survival with reduced toxicity through treatment selection based on risk stratification and prognostic biomarkers is incrementally evolving.