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The choice of DIR algorithm was limited to those available in the RayStation 9B Treatment Planning System. However, these algorithms are representative of the range of approaches available commercially, encompassing grey-scale driven (correlation and mutual information), biomechanical and contour-driven methods. The Anaconda algorithm is capable of combining greyscale and contour registration and, herein, we have additionally combined biomechanical registration with Anaconda.Whilst many other DIR software platforms and algorithms exist, these do not fundamentally differ from the algorithms used here. Our focus was to explore the potential for combinations of existing DIR methods to overcome challenges in the case of extreme pelvic anatomical changes, so we have not attempted an algorithmic comparison. However, we would expect our findings to apply to any combination of similar grey-scale and biomechanical DIR algorithms in other contexts and systems, given an appropriate workflow as outlined below. 2 and Figure 3 and 4): DIR results (see also Supplementary Table Jacobian analysis:Clinical significance for reRT was assessed by overlaying the negative element mask onto the reRT CT image and combined dose distribution. In two cases the folding was <1 grid voxel (2.5 mm) and clinically insignificant. In one case, folding ~20 mm was observed, along the bladder-rectal interface. This case fell >3 s.d. from the mean for bladder DSC (0.

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