Combining Systemic Therapy With Radiation: Head and Neck Cancer Treatments in an Era of Targeted Agents and Immunotherapy

The addition of chemotherapy to radiation therapy (RT) has been established for decades to improve outcomes in patients with head and neck cancer (HNC). Concurrent chemoradiation increases both local control and overall survival but at the cost of significant toxicity, motivating extensive investigations to optimize the balance of clinical efficacy and adverse effects. This review discusses the rationale and seminal studies underlying the concurrent chemoradiation treatment paradigm in HNC, and describes attempts to better tailor systemic therapy beyond standard-of-care cisplatin, such as the use of alternate cytotoxic agents and nonstandard dosing regimens. Modern efforts to incorporate targeted therapies and immunotherapy are then summarized, particularly for patients unable to receive standard cytotoxic chemotherapy. Finally, mechanisms through which RT and systemic therapy cooperate to improve the therapeutic ratio are discussed, with a focus on the interaction between immunotherapy and RT, a rapidly emerging treatment paradigm. With increasing application of novel diagnostic and therapeutic approaches, determining the optimal concurrent systemic program to maximize RT efficacy will continue to evolve. Identification of patient- and tumor-specific factors will offer a unique opportunity to implement personalized oncologic care.