{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:09:48Z","timestamp":1768568988148,"version":"3.49.0"},"posted":{"date-parts":[[2025,6,20]]},"group-title":"Oncology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background &amp; purpose<\/jats:title>\n                  <jats:p>Late radiation-associated dysphagia after head and neck cancer (HNC) significantly impacts patient\u2019s health and quality of life. Conventional normal tissue complication probability (NTCP) models use discrete dose parameters to predict toxicity risk but fail to fully capture the complexity of this side effect. Deep learning (DL) offers potential improvements by incorporating 3D dose data for all anatomical structures involved in swallowing. This study aims to enhance dysphagia prediction with 3D DL NTCP models compared to conventional NTCP models.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Materials &amp; methods<\/jats:title>\n                  <jats:p>A multi-institutional cohort of 1484 HNC patients was used to train and validate a 3D DL model (Residual Network) incorporating 3D dose distributions, organ-at-risk segmentations, and CT scans, with or without patient- or treatment-related data. Predictions of grade \u22652 dysphagia (CTCAEv4) at six months post-treatment were evaluated using area under the curve (AUC) and calibration curves. Results were compared to a conventional NTCP model based on pre-treatment dysphagia, tumour location, and mean dose to swallowing organs. Attention maps highlighting regions of interest for individual patients were assessed.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>DL models outperformed the conventional NTCP model in both the independent test set (AUC=0.80-0.84 versus 0.76) and external test set (AUC=0.73-0.74 versus 0.63) in AUC and calibration. Attention maps showed a focus on the oral cavity and superior pharyngeal constrictor muscle.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>DL NTCP models performed better than the conventional NTCP model, suggesting the benefit of using 3D-input over the conventional discrete dose parameters. Attention maps highlighted relevant regions linked to dysphagia, supporting the utility of DL for improved predictions.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.20.25329926","type":"posted-content","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T18:15:19Z","timestamp":1750443319000},"source":"Crossref","is-referenced-by-count":1,"title":["Deep learning NTCP model for late dysphagia after radiotherapy for head and neck cancer patients based on 3D dose, CT and segmentations"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-2898","authenticated-orcid":false,"given":"S.P.M.","family":"de Vette","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-1810","authenticated-orcid":false,"given":"H.","family":"Neh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9866-4527","authenticated-orcid":false,"given":"L.","family":"van der Hoek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4935-1373","authenticated-orcid":false,"given":"D.C.","family":"MacRae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-8980","authenticated-orcid":false,"given":"H.","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4564-7858","authenticated-orcid":false,"given":"A.","family":"Gawryszuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-778X","authenticated-orcid":false,"given":"R.J.H.M.","family":"Steenbakkers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8995-1210","authenticated-orcid":false,"given":"P.M.A.","family":"van Ooijen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5264-3994","authenticated-orcid":false,"given":"C.D.","family":"Fuller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3710-5706","authenticated-orcid":false,"given":"K.A.","family":"Hutcheson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-372X","authenticated-orcid":false,"given":"J.A.","family":"Langendijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-274X","authenticated-orcid":false,"given":"N.M.","family":"Sijtsema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-5616","authenticated-orcid":false,"given":"L.V.","family":"van Dijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025062300452119000_2025.06.20.25329926v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.04.011"},{"key":"2025062300452119000_2025.06.20.25329926v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anorl.2013.09.006"},{"key":"2025062300452119000_2025.06.20.25329926v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2011.08.009"},{"key":"2025062300452119000_2025.06.20.25329926v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.01.024"},{"key":"2025062300452119000_2025.06.20.25329926v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.06.035"},{"key":"2025062300452119000_2025.06.20.25329926v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.05.007"},{"key":"2025062300452119000_2025.06.20.25329926v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.10.028"},{"key":"2025062300452119000_2025.06.20.25329926v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.09.022"},{"key":"2025062300452119000_2025.06.20.25329926v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2008.06.001"},{"key":"2025062300452119000_2025.06.20.25329926v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.06.004"},{"key":"2025062300452119000_2025.06.20.25329926v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.10.028"},{"key":"2025062300452119000_2025.06.20.25329926v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-013-9452-2"},{"key":"2025062300452119000_2025.06.20.25329926v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.01.019"},{"key":"2025062300452119000_2025.06.20.25329926v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.04.012"},{"key":"2025062300452119000_2025.06.20.25329926v1.15","doi-asserted-by":"publisher","DOI":"10.3390\/math10081283"},{"key":"2025062300452119000_2025.06.20.25329926v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-2660-4_40"},{"key":"2025062300452119000_2025.06.20.25329926v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2021.06.020"},{"key":"2025062300452119000_2025.06.20.25329926v1.18","doi-asserted-by":"publisher","DOI":"10.1002\/lio2.676"},{"key":"2025062300452119000_2025.06.20.25329926v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.06.009"},{"key":"2025062300452119000_2025.06.20.25329926v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2024.07.2334"},{"key":"2025062300452119000_2025.06.20.25329926v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.05.004"},{"key":"2025062300452119000_2025.06.20.25329926v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2015.07.041"},{"key":"2025062300452119000_2025.06.20.25329926v1.23","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.14132871"},{"key":"2025062300452119000_2025.06.20.25329926v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.09.022"},{"key":"2025062300452119000_2025.06.20.25329926v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2025.107224"},{"key":"2025062300452119000_2025.06.20.25329926v1.26","unstructured":"He K , Zhang X , Ren S , Sun J. Deep Residual Learning for Image Recognition. Published online December 10, 2015. http:\/\/arxiv.org\/abs\/1512.03385"},{"key":"2025062300452119000_2025.06.20.25329926v1.27","doi-asserted-by":"publisher","DOI":"10.1145\/3292500.3330701"},{"key":"2025062300452119000_2025.06.20.25329926v1.28","unstructured":"Hendrycks D , Mu N , Cubuk ED , Zoph B , Gilmer J , Lakshminarayanan B. AugMix: A Simple Data Processing Method to Improve Robustness and Uncertainty. Published online December 5, 2019. http:\/\/arxiv.org\/abs\/1912.02781"},{"key":"2025062300452119000_2025.06.20.25329926v1.29","unstructured":"Cardoso MJ , Li W , Brown R , et al. MONAI: An open-source framework for deep learning in healthcare. Published online November 4, 2022. http:\/\/arxiv.org\/abs\/2211.02701"},{"key":"2025062300452119000_2025.06.20.25329926v1.30","doi-asserted-by":"publisher","DOI":"10.5555\/3454287.3455008"},{"key":"2025062300452119000_2025.06.20.25329926v1.31","doi-asserted-by":"publisher","DOI":"10.1109\/WACV.2018.00097"},{"key":"2025062300452119000_2025.06.20.25329926v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2025.110871"},{"key":"2025062300452119000_2025.06.20.25329926v1.33","doi-asserted-by":"publisher","DOI":"10.1007\/s42058-024-00142-3"},{"key":"2025062300452119000_2025.06.20.25329926v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2022.03.009"},{"key":"2025062300452119000_2025.06.20.25329926v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.09.022"},{"key":"2025062300452119000_2025.06.20.25329926v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.09.017"},{"key":"2025062300452119000_2025.06.20.25329926v1.37","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-021-10307-2"},{"key":"2025062300452119000_2025.06.20.25329926v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.06.013"},{"key":"2025062300452119000_2025.06.20.25329926v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30283"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.20.25329926","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:38:55Z","timestamp":1768509535000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.06.20.25329926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1101\/2025.06.20.25329926","relation":{},"subject":[],"published":{"date-parts":[[2025,6,20]]},"subtype":"preprint"}}