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. 2017 Aug 3;7:7220. doi: 10.1038/s41598-017-07586-x

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic flowchart of the voxel-based (VB) analysis (upper panel) and of its treatment planning (TP) application (lower panel) in head and neck (HN) cancer patients. Planning CTs are registered to the common coordinate system (CCS) by an elastic image registration (EIR) tool. The obtained deformation fields are used to warp the dose maps into the CCS. A statistical mapping scheme (TFCE) is applied to extract the clusters of voxels (S _0.05) significantly associated with higher doses released in patients developing the radiation-induced toxicity. For any new HN patient (case patient), the S _0.05 region is warped as a new avoidance structure into the DICOM-RT object according to the deformation field that maps the CCS into the considered planning CT, and the corresponding mean dose (D_mean,S0.05) is used as planning constraint.