Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCT) and the soft tissue prostate (CBCT). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCT and CBCT was performed by three RTs. Inter-observer agreement was assessed using a modified Bland-Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoA) were defined as ±2.0 mm for CBCT and ±3.0 mm for CBCT. Differences between CBCT alignment and the observer-averaged CBCT (AvCBCT) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCT and AvCBCT. Results CBCT and CBCT alignments were performed for 185 images. The CBCT 95% LoA were within ±2.0 mm in all planes. CBCT 95% LoA were within ±3.0 mm in all planes. Comparison of CBCT with AvCBCT resulted in 95% LoA of -4.9 to 2.6, -1.6 to 2.5 and -4.7 to 1.9 mm in the superior-inferior, left-right and anterior-posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy
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