Purpose: To investigate interfraction setup variations of the primary tumor, elective nodes, and vertebrae in laryngeal cancer patients and to validate protocols for cone beam computed tomography ... Show morePurpose: To investigate interfraction setup variations of the primary tumor, elective nodes, and vertebrae in laryngeal cancer patients and to validate protocols for cone beam computed tomography (CBCT)-guided correction.Methods and Materials: For 30 patients, CBCT-measured displacements in fractionated treatments were used to investigate population setup errors and to simulate residual setup errors for the no action level (NAL) offline protocol, the extended NAL (eNAL) protocol, and daily CBCT acquisition with online analysis and repositioning.Results: Without corrections, 12 of 26 patients treated with radical radiation therapy would have experienced a gradual change (time trend) in primary tumor setup >= 4 mm in the cranio-caudal (CC) direction during the fractionated treatment (11/12 in caudal direction, maximum 11 mm). Due to these trends, correction of primary tumor displacements with NAL resulted in large residual CC errors (required margin 6.7 mm). With the weekly correction vector adjustments in eNAL, the trends could be largely compensated (CC margin 3.5 mm). Correlation between movements of the primary and nodal clinical target volumes (CTVs) in the CC direction was poor (r(2) = 0.15). Therefore, even with online setup corrections of the primary CTV, the required CC margin for the nodal CTV was as large as 6.8 mm. Also for the vertebrae, large time trends were observed for some patients. Because of poor CC correlation (r(2) = 0.19) between displacements of the primary CTV and the vertebrae, even with daily online repositioning of the vertebrae, the required CC margin around the primary CTV was 6.9 mm.Conclusions: Laryngeal cancer patients showed substantial interfraction setup variations, including large time trends, and poor CC correlation between primary tumor displacements and motion of the nodes and vertebrae (internal tumor motion). These trends and nonrigid anatomy variations have to be considered in the choice of setup verification protocol and planning target volume margins. eNAL could largely compensate time trends with minor prolongation of fraction time. (c) 2013 Elsevier Inc. Show less