Emerging Radiotherapy Technologies for Head and Neck Squamous Cell Carcinoma: Challenges and Opportunities in the Era of Immunotherapy.

Radiotherapy (RT) is an integral component in the multidisciplinary management of patients with head and neck squamous cell carcinoma (HNSCC). Significant advances have been made toward optimizing tumor control and toxicity profiles of RT for HNSCC in the past two decades. The development of intensity modulated radiotherapy (IMRT) and concurrent chemotherapy established the standard of care for most patients with locally advanced HNSCC around the turn of the century. More recently, selective dose escalation to the most radioresistant part of tumor and avoidance of the most critical substructures of organs at risk, often guided by functional imaging, allowed even further improvement in the therapeutic ratio of IMRT. Other highly conformal RT modalities, including intensity modulated proton therapy (IMPT) and stereotactic body radiotherapy (SBRT) are being increasingly utilized, although there are gaps in our understanding of the normal tissue complication probabilities and their relative biological effectiveness. There is renewed interest in spatially fractionated radiotherapy (SFRT), such as GRID and LATTICE radiotherapy, in both palliative and definitive settings. The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with recurrent and metastatic HNSCC. Novel RT modalities, including IMPT, SBRT, and SFRT, have the potential to reduce lymphopenia and immune suppression, stimulate anti-tumor immunity, and synergize with ICIs. The next frontier in the treatment of HNSCC may lie in the exploration of combined modality treatment with new RT technologies and ICIs.