Integration of radiation therapy with systemic treatments in head and neck cancer: expert opinion and roadmap to consensus.

Abstract

Integration of radiation therapy (RT) with systemic treatments in head and neck cancers has transformed therapeutic paradigms, yet optimal combinations remain undefined. This study aimed to identify priority areas of unmet need in combining RT with systemic treatment in both squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal cancer (NPC). A multidisciplinary panel of international experts in radiation, clinical, and medical oncology convened to identify priority areas of unmet need. Four clinical scenarios were evaluated: locally-advanced (LA) SCCHN; recurrent/metastatic (R/M) SCCHN; LA NPC; and R/M NPC. Experts ranked a predefined shortlist of topics using weighted Borda count methodology and proposed ideal clinical trial designs to address the identified unmet needs. Fifteen expert responses identified eight priority topics across the four scenarios. In locally-advanced SCCHN, top priorities included risk-adapted prognostic evaluation at diagnosis and personalized chemoradiation following peri-operative immunotherapy. For R/M SCCHN, experts highlighted the role of locoregional radiation in de-novo metastatic disease on first-line therapy and treatment sequencing in oligometastatic programmed death ligand-1 (PD-L1) combined positive score (CPS)-positive disease as the key need. In LA NPC, the leading topics were patient selection for intensification strategies and for de-escalation after induction chemo-immunotherapy. In R/M NPC, experts prioritized sequencing locoregional RT and metastasis-directed therapy in patients with de-novo oligometastatic disease who are benefiting from first-line treament. This study defines critical knowledge gaps in integrating RT with systemic treatments in head and neck cancer, and provides a roadmap for future international consensus development and clinical research to advance personalized treatment strategies.