PURPOSEThis study aims to quantify the variation in dose-volume histogram (DVH) and normal tissue complication probability(NTCP) metrics for head-and-neck (HN) cancer patients when alternative organ-at-risk(OAR) delineations are used for treatment planning and for treatment plan evaluation. We particularly focus on the effects of daily patient positioning/setup variations(SV) in relation to treatment technique and delineation variability.MATERIALS AND METHODSWe generated two-arc VMAT, 5-beam IMRT, and 9-beam IMRT treatment plans for a cohort of 209 HN patients. These plans incorporated five different OAR delineation sets, including manual and four automated algorithms. Each treatment plan was assessed under various simulated per-fraction patient setup uncertainties, evaluating the potential clinical impacts through DVH and NTCP metrics.RESULTSThe study demonstrates that increasing SV generally reduces differences in DVH metrics between alternative delineations. However, in contrast, differences in NTCP metrics tend to increase with higher setup variability. This pattern is observed consistently across different treatment plans and delineator combinations, illustrating the intricate relationship between SV and delineation accuracy. Additionally, the need for delineation accuracy in treatment planning is shown to be case-specific and dependent on factors beyond geometric variations.CONCLUSIONSThe findings highlight the necessity for comprehensive Quality Assurance programs in radiotherapy, incorporating both dosimetric impact analysis and geometric variation assessment to ensure optimal delineation quality. The study emphasizes the complex dynamics of treatment planning in radiotherapy, advocating for personalized, case-specific strategies in clinical practice to enhance patient care quality and efficacy in the face of varying SV and delineation accuracies.