"Patient-specific validation of deformable image registration in radiation therapy: Overview and caveats".

Over the last few decades, deformable image registration (DIR) has gained popularity in image-guided radiation therapy for a number of applications, such as contour propagation, dose warping, and accumulation. Although this raises promising perspectives for the improvement of treatment outcomes and quality of radiotherapy clinical practice, the variety of proposed DIR algorithms, combined with the lack of an effective quantitative quality control metric of the registration, is slowing the transfer of DIR into the clinical routine. Recently, a task group (AAPM TG132) report was published outlining the essential aspects of DIR for image guidance in radiotherapy. However, an accurate and efficient patient-specific validation is not yet defined, and appropriate metrics should be identified to achieve the definition of both geometric and dosimetric accuracy. In this respect, the use of a dense set of anatomical landmarks, along with additional evaluations on contours or deformation field analysis, are likely to drive patient-specific DIR validation in clinical image-guided radiotherapy applications to account for geometric inaccuracies. Automatic and efficient strategies able to provide spatial information of DIR uncertainties and to evaluate monomodal and multimodal image registration, as well as to describe homogenous and un-contrasted regions are believed to represent the future direction in DIR validation. But especially in the case of DIR applications for dose mapping and accumulation, the need of accurate patient-specific validation is not only limited to the evaluation of geometric accuracy. In fact, the need to account for dosimetric inaccuracies due to DIR represents another important area in the field of adaptive treatments. Different approaches are currently being investigated to quantify the effect of DIR error on dose analysis, mainly relying on clinically relevant dose metrics, or on the study of deformation field properties for a voxel-by-voxel evaluation. However, novel research is required for the definition of dedicated and personalized measures capable to relate the geometric and dosimetric inaccuracies, thus bearing useful information for a safe use of DIR by clinical end users. In this paper we provide insights on DIR results evaluation on a patient-specific basis, facing the issues of both geometric and dosimetric paradigms. Challenges on DIR validation are overviewed and discussed, in order to push preliminary clinical guidelines forward on this fundamental topic and boost the implementation of more robust and reliable patient-specific evaluation metrics.