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The purpose of this study was to investigate the number of intermediate states required to adequately approximate the clinically relevant cumulative dose to deforming/moving thoracic anatomy in four-dimensional (4D) conformal radiotherapy that uses 6 MV photons to target tumors. Four patients were involved in this study. For the first three patients, computed tomography images acquired at exhale and inhale were available; they were registered using B-spline deformation model and the computed transformation was further used to simulate intermediate states between exhale and inhale. For the fourth patient, 4D-acquired, phase-sorted datasets were available and each dataset was registered with the exhale dataset. The exhale-inhale transformation was also used to simulate intermediate states in order to compare the cumulative doses computed using the actual and the simulated datasets. Doses to each state were calculated using the Dose Planning Method (DPM) Monte Carlo code and dose was accumulated for scoring on the exhale anatomy via the transformation matrices for each state and time weighting factors. Cumulative doses were estimated using increasing numbers of intermediate states and compared to simpler scenarios such as a “2-state” model which used only the exhale and inhale datasets or the dose received during the average phase of the breathing cycle. Dose distributions for each modeled state as well as the cumulative doses were assessed using dose volume histograms and several treatment evaluation metrics such as mean lung dose, normal tissue complication probability, and generalized uniform dose. Although significant “point dose” differences can exist between each breathing state, the differences decrease when cumulative doses are considered, and can become less significant yet in terms of evaluation metrics depending upon the clinical end point. This study suggests that for certain “clinical” end points of importance for lung cancer, satisfactory predictions of accumulated total dose to be received by the distorting anatomy can be achieved by calculating the dose to but a few (or even simply the average) phases of the breathing cycle. [ABSTRACT FROM AUTHOR]