## 5 Conclusions  
A novel method to evaluate the quality of patient-specific multimodality CT-CBCT DIR for the adaptive radiotherapy of HN patients, based on the clinical observed changes as the ground truth, has been developed, using a digitally enhanced anthropomorphic phantom to include the common organs at risk. An established workflow and operative\(\backslash\) tolerance level, based on the TG132 indications, were provided. The methodology allows the direct testing of the patient-specific DIR spatial and dosimetric accuracy at the voxel level, which can produce valuable insights into their clinical impact on the adapted dose distribution.  
The method was applied to test the DIR performance on a set of clinical HN patients using clinical commercial software. It was found that the DIR performance varied with the specific registration and organ, and the complex relationship between the spatial and dose errors. The results of this study suggest that the method is suitable to assess the adequacy of the DIR-based dose accumulation.  
The technical requirement for using this method is the availability of an independent image registration software platform (in addition to the clinical system) and the processed phantom image sets. This work contributes to the study of the standardisation and automation of quality assurance methods for deformable image registration in radiotherapy.  
**Supplementary Materials:** The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app12199493/s1](https://www.mdpi.com/article/10.3390/app12199493/s1)]([https://www.mdpi.com/article/10.3390/app12199493/s1](https://www.mdpi.com/article/10.3390/app12199493/s1)).
* [2]**Author Contributions:** Conceptualization, E.C., A.B. and M.I.; methodology, E.C., A.B., G.L. and E.S.; investigation, E.C. and A.B.; resources, M.O. and M.G.; data curation, E.C., A.B., G.L and E.S.; writing--original draft preparation, E.C., G.L. and E.S.; writing--review and editing, G.L. and E.S.; supervision, C.I., M.I., E.S. and G.L. All authors have read and agreed to the published version of the manuscript.
* [3]**Funding:** This study was partially supported by Italian Ministry of Health-Ricerca Corrente.
* [4]**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Azienda USLRICCS di Reggio Emilia (with protocol code n. 2016/0014486, Date 30 May 2016).
* [5]**Informed Consent Statement:** Patient consent was waived because of the retrospective design of the study and to the impossibility of providing the informed consent statement to each subject involved in the protocol study, due to the high number of interested parties (Italian law, Legislative Decree 196/2003, Art.110 and Deliberazione del Garante Privacy n. 85 on 1 March 2012 (published in the GU on 26 March 2012)).
* [6]**Data Availability Statement:** The data are available from the corresponding author.
* [7]**Acknowledgments:** The authors would like to thank ELSE Solutions (Trezzano (MI), Italy) and CIRS (Norfolk, VA, USA) for providing the ATOM Max TM Dental and Diagnostic Head Phantom Model-711 used for this study. The authors would also like to thank [PERSON] for his technical support and [PERSON] for her useful comments on the manuscript.
* [8]**Conflicts of Interest:** The authors declare no conflict of interest.