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Based on multicentre cohorts for exploration (206 patients) and independent validation (85 patients), multiple deep learning strategies including training of 3D- and 2D-convolutional neural networks (CNN) from scratch, transfer learning and extraction of deep autoencoder features were assessed and compared to a clinical model. Analyses were based on Cox proportional hazards regression and model performances were assessed by the concordance index (C-index) and the model\u2019s ability to stratify patients based on predicted hazards of LRC. Among all models, an ensemble of 3D-CNNs achieved the best performance (C-index 0.31) with a significant association to LRC on the independent validation cohort. It performed better than the clinical model including the tumour volume (C-index 0.39). Significant differences in LRC were observed between patient groups at low or high risk of tumour recurrence as predicted by the model (<jats:inline-formula><jats:alternatives><jats:tex-math>$$p=0.001$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mrow>\n                    <mml:mi>p<\/mml:mi>\n                    <mml:mo>=<\/mml:mo>\n                    <mml:mn>0.001<\/mml:mn>\n                  <\/mml:mrow>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula>). This 3D-CNN ensemble will be further evaluated in a currently ongoing prospective validation study once follow-up is complete.<\/jats:p>","DOI":"10.1038\/s41598-020-70542-9","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T10:04:50Z","timestamp":1600941890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["2D and 3D convolutional neural networks for outcome modelling of locally advanced head and neck squamous cell carcinoma"],"prefix":"10.1038","volume":"10","author":[{"given":"Sebastian","family":"Starke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Leger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Zwanenburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karoline","family":"Leger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Lohaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annett","family":"Linge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goda","family":"Kalinauskaite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"Tinhofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nika","family":"Guberina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Guberina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Balermpas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"von der Gr\u00fcn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Ganswindt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Belka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan C.","family":"Peeken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie E.","family":"Combs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Boeke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Zips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Richter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther G. 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For the present manuscript, Dr. Linge confirms that this above mentioned funding source was not involved. Dr. Richter received individual funding as lecturer from Siemens Healthineers (2018). OncoRay has institutional research agreements with Siemens Healthineers. Furthermore, OncoRay has an institutional agreement as reference center for dual-energy CT in radiotherapy as well as a software evaluation contract with Siemens Healthineers. In the past 5 years, Dr. Krause received funding for her research Projects by IBA (2016), Merck KGaA (2014\u20132018 for preclinical study; 2018-2020 for clinical study), Medipan GmbH (2014\u20132018). In the past 5 years, Dr. Troost, Dr. Krause and Dr. L\u00f6ck have been involved in an ongoing publicly funded (German Federal Ministry of Education and Research) Project with the companies Medipan, Attomol GmbH, GA Generic Assays GmbH, Gesellschaft f\u00fcr medizinische und wissenschaftliche genetische Analysen, Lipotype GmbH and PolyAn GmbH (2019\u20132021). For the present manuscript, none of the above mentioned funding sources were involved. In the past 5 years, Dr. Baumann attended an advisory board meeting of MERCK KGaA (Darmstadt), for which the University of Dresden received a travel grant. He further received funding for his research Projects and for educational grants to the University of Dresden by Teutopharma GmbH (2011\u20132015), IBA (2016), Bayer AG (2016\u20132018), Merck KGaA (2014\u20132030), Medipan GmbH (2014-2018). For the German Cancer Research Center (DKFZ, Heidelberg) Dr. Baumann is on the supervisory boards of HI-STEM gGmbH (Heidelberg). Dr. Baumann, as former chair of OncoRay (Dresden) and present CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg), was or is responsible for collaborations with a multitude of companies and institutions, worldwide. In this capacity, he has signed\/signs contracts for his institute(s) and for the staff for research funding and\/or collaborations with industry and academia, worldwide. In this role, he was\/is further responsible for commercial technology transfer activities of his institute(s), including patent and other similar IP portfolios. Dr. Baumann confirms that none of the above funding sources were involved in the preparation of this paper. University Department of Radiation Oncology T\u00fcbingen receives financial and technical support from Elekta AB (Stockholm, Sweden) under a research agreement. The other authors have nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15625"}}