Differential associations between treatment delay and survival across head and neck cancer subsites: a national hospital-based framework for risk-stratified prioritization

Purpose Delays in time to treatment initiation (TTI) have been associated with inferior outcomes in head and neck cancer, yet prior studies have typically evaluated tumors collectively, assuming uniform time sensitivity across diseases. This study quantified subsite- and stage-specific associations between TTI and overall survival (OS) and derived groups of tumors with similar TTI-mortality associations. Methods We conducted a retrospective cohort study using the National Cancer Database (2010–2017), including adults with head and neck malignancies treated with curative intent. Multivariable Cox models estimated adjusted hazard ratios (HRs) for OS across each subsite–stage combination. Tumors were clustered according to the TTI threshold at which mortality risk became significantly elevated. Results The cohort included 211,406 patients. Early-stage tongue, floor of the mouth and glottic tumors, along with advanced tonsil and base of tongue cancers, showed increased mortality when TTI exceeded 30 days, forming the most time-sensitive category. Other tumors showed increased mortality at 60 days or 90 days. Salivary gland, lip and most advanced cancers showed no significant increase in mortality until ≥120 days. OS trajectories varied across the derived groups, reflecting heterogeneous associations between treatment timing and survival. Conclusion Treatment delay has heterogeneous associations with mortality across head and neck subsites and stages. This derived framework identifies four TTI-sensitivity groups based on the timing at which excess adjusted mortality was observed. These findings may inform risk-stratified prioritization when treatment capacity is constrained but should not be interpreted as evidence that intentional treatment delay is clinically safe.