BackgroundIn patients with head-neck cancer treated with IMRT, immobility of the upper part of the body during radiation is maintained by means of customised immobilisation devices.The main purpose of this study was to determine how the procedures for preparation of customised immobilisation systems and the patients characteristics influence the extent of setup errors.MethodsA longitudinal, prospective study involving 29 patients treated with IMRT. Data were collected before CT simulation and during all the treatment sessions (528 setup errors analysed overall); the correlation with possible risk factors for setup errors was explored using a linear mixed model.ResultsSetup errors were not influenced by the patient’s anxiety and pain. Temporary removal of the thermoplastic mask before carrying out the CT simulation shows statistically borderline, clinically relevant, increase of setup errors (+24.7%, 95% CI: −0.5% - 55.8%). Moreover, a unit increase of radiation therapists who model the customised thermoplastic mask is associated to a −18% (−29.2% - -4.9%) reduction of the errors.The setup error is influenced by the patient’s physical features; in particular, it increases both in patients in whom the treatment position is obtained with ‘Shoulder down’ (+27.9%, 2.2% - 59.7%) and in patients with ‘Scoliosis/kyphosis’ problems (+65.4%, 2.3% - 164.2%). Using a ‘Small size standard plus customized neck support device’ is associated to a −52.3% (−73.7% - -11.2%) reduction.The increase in number of radiation therapists encountered during the entire treatment cycle does not show associations. Increase in the body mass index is associated with a slight reduction in setup error by (−2.8%, −5% - -0.7%).ConclusionThe position of the patient obtained by forcing the shoulders downwards, clinically significant scoliosis or kyphosis and the reduction of the number of radiation therapists who model the thermoplastic mask are found to be statistically significant risk factors that can cause an increase in setup errors, while the use of ‘Small size’ neck support device and patient BMI can diminish them.