Principles and Paradigms of De-Escalated Elective Nodal Irradiation: Boldly Going Towards an Inflection Point in Head and Neck Radiotherapy

Fundamental axioms of elective nodal irradiation (ENI) for head and neck cancers merit re-examination in contemporary practice. Standard ENI doses to volumes bordering critical organs-at-risk increased during the transition from two-dimensional radiation planning to intensity-modulated radiotherapy, despite improvements in detection of occult nodal metastases with modern imaging, use of concurrent chemotherapy, and identification of human papillomavirus (HPV)-related radiosensitivity. Historical large ENI volumes covering low-risk nodal regions continue to be commonly used even as awareness grows regarding the predominant pattern-of-failure within existing gross disease. In this review, we outline principles for de-escalating head and neck ENI dose and volume and highlight the emerging paradigm of ENI omission. We also propose a three-part approach to ENI de-escalation, the rationale for early adoption of de-escalated ENI in the absence of level-one evidence, and strategies to promote early adoption in light of modest equipoise and an inflection point towards changing the status quo.