{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:47:23Z","timestamp":1786996043842,"version":"build-2736575974"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003006","name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","doi-asserted-by":"publisher","award":["185082"],"award-info":[{"award-number":["185082"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thegreenjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Radiotherapy and Oncology"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.radonc.2022.09.021","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T12:16:55Z","timestamp":1665404215000},"page":"208-214","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer"],"prefix":"10.1016","volume":"176","author":[{"given":"Andreas","family":"K\u00f6the","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony John","family":"Lomax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Giovannelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairos","family":"Safai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Bizzocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Roelofs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniek J.G.","family":"Even","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien Charles","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Fattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.radonc.2022.09.021_b0005","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1634\/theoncologist.9-90005-4","article-title":"Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response","volume":"9","author":"Vaupel","year":"2004","journal-title":"Oncologist"},{"key":"10.1016\/j.radonc.2022.09.021_b0010","doi-asserted-by":"crossref","first-page":"20130676","DOI":"10.1259\/bjr.20130676","article-title":"Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response","volume":"87","author":"McKeown","year":"2014","journal-title":"Br J Radiol"},{"key":"10.1016\/j.radonc.2022.09.021_b0015","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/djx160","article-title":"Targeting hypoxia to improve non\u2013small cell lung cancer outcome","volume":"110","author":"Salem","year":"2018","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.radonc.2022.09.021_b0020","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.semradonc.2014.11.006","article-title":"Hypoxia as a Cause of Treatment Failure in Non-Small Cell Carcinoma of the Lung","volume":"25","author":"Brustugun","year":"2015","journal-title":"Semin Radiat Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0025","doi-asserted-by":"crossref","first-page":"17016","DOI":"10.1038\/srep17016","article-title":"Kill-painting of hypoxic tumours in charged particle therapy","volume":"5","author":"Tinganelli","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.radonc.2022.09.021_b0030","doi-asserted-by":"crossref","first-page":"045008","DOI":"10.1088\/1361-6560\/aafe40","article-title":"Kill painting of hypoxic tumors with multiple ion beams","volume":"64","author":"Sokol","year":"2019","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.radonc.2022.09.021_b0035","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ijrobp.2009.04.028","article-title":"Intensity-Modulated Proton Therapy Reduces the Dose to Normal Tissue Compared With Intensity-Modulated Radiation Therapy or Passive Scattering Proton Therapy and Enables Individualized Radical Radiotherapy for Extensive Stage IIIB Non-Small-Cell Lung Canc","volume":"77","author":"Zhang","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0040","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13014-021-01914-2","article-title":"Investigating the potential of proton therapy for hypoxia-targeted dose escalation in non-small cell lung cancer","volume":"16","author":"K\u00f6the","year":"2021","journal-title":"Radiat Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0045","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1118\/1.4916662","article-title":"Motion mitigation for lung cancer patients treated with active scanning proton therapy","volume":"42","author":"Grassberger","year":"2015","journal-title":"Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0050","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.3390\/cancers7030829","article-title":"Tumour Movement in Proton Therapy: Solutions and Remaining Questions: A Review","volume":"7","author":"De Ruysscher","year":"2015","journal-title":"Cancers"},{"key":"10.1016\/j.radonc.2022.09.021_b0055","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.radonc.2021.01.014","article-title":"Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information","volume":"157","author":"Ribeiro","year":"2021","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0060","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1088\/0031-9155\/60\/20\/8141","article-title":"Improving 4D plan quality for PBS-based liver tumour treatments by combining online image guided beam gating with rescanning","volume":"60","author":"Zhang","year":"2015","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.radonc.2022.09.021_b0065","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.ijrobp.2015.11.015","article-title":"Robustness of the voluntary breath-hold approach for the treatment of peripheral lung tumors using hypofractionated pencil beam scanning proton therapy","volume":"95","author":"Dueck","year":"2016","journal-title":"Int J Radiat Oncol* Biol* Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0070","first-page":"110","article-title":"The potential of Gantry beamline large momentum acceptance for real time tumour tracking in pencil beam scanning proton therapy","volume":"10","author":"Fattori","year":"2020","journal-title":"Sci Reports"},{"key":"10.1016\/j.radonc.2022.09.021_b0075","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1088\/0031-9155\/54\/21\/007","article-title":"Tumour tracking with scanned proton beams: Assessing the accuracy and practicalities","volume":"54","author":"Van De Water","year":"2009","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.radonc.2022.09.021_b0080","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.zemedi.2019.10.003","article-title":"Performance of Makerless Tracking for Gimbaled Dynamic Tumor Tracking","volume":"30","author":"Ziegler","year":"2020","journal-title":"Z Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0085","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.radonc.2015.07.013","article-title":"PET-based dose painting in non-small cell lung cancer: Comparing uniform dose escalation with boosting hypoxic and metabolically active sub-volumes","volume":"116","author":"Even","year":"2015","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0090","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ejmp.2020.07.003","article-title":"The FLUKA Monte Carlo code coupled with an OER model for biologically weighted dose calculations in proton therapy of hypoxic tumors","volume":"76","author":"Dahle","year":"2020","journal-title":"Phys Medica"},{"key":"10.1016\/j.radonc.2022.09.021_b0095","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1118\/1.2966347","article-title":"Reconstruction of a time-averaged midposition CT scan for radiotherapy planning of lung cancer patients using deformable registrationa)","volume":"35","author":"Wolthaus","year":"2008","journal-title":"Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0100","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.radonc.2020.09.035","article-title":"Clinical implementation of pencil beam scanning proton therapy for liver cancer with forced deep expiration breath hold","volume":"154","author":"Fracchiolla","year":"2021","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13014-016-0640-8","article-title":"Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: Phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC","volume":"11","author":"Giaddui","year":"2016","journal-title":"Radiat Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0110","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.radonc.2006.08.009","article-title":"An \u201cin silico\u201d clinical trial comparing free breathing, slow and respiration correlated computed tomography in lung cancer patients","volume":"81","author":"Bosmans","year":"2006","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0115","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/JTO.0b013e31823529fc","article-title":"Results of a Multicentric In Silico Clinical Trial (ROCOCO): Comparing Radiotherapy with Photons and Protons for Non-small Cell Lung Cancer","volume":"7","author":"Roelofs","year":"2012","journal-title":"J Thorac Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0120","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.semradonc.2003.10.003","article-title":"Errors and margins in radiotherapy","volume":"14","author":"Van Herk","year":"2004","journal-title":"Semin Radiat Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0125","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/j.ijrobp.2008.02.079","article-title":"Experiences at the Paul Scherrer Institute With a Remote Patient Positioning Procedure for High-Throughput Proton Radiation Therapy","volume":"71","author":"Bolsi","year":"2008","journal-title":"Int J Radiat Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0130","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1118\/1.1779371","article-title":"Treatment planning and verification of proton therapy using spot scanning: Initial experiences","volume":"31","author":"Lomax","year":"2004","journal-title":"Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0135","doi-asserted-by":"crossref","unstructured":"International Commission of Radiation Units and Measurements. Geometric terms and dose, and dose-volume definitions. J ICRU 2007:83\u201394.","DOI":"10.1093\/jicru_ndm028"},{"key":"10.1016\/j.radonc.2022.09.021_b0140","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.3109\/0284186X.2014.906747","article-title":"Prescribing and evaluating target dose in dose-painting treatment plans","volume":"53","author":"H\u00e5kansson","year":"2014","journal-title":"Acta Oncol (Madr)"},{"key":"10.1016\/j.radonc.2022.09.021_b0145","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1118\/1.598063","article-title":"Reporting and analyzing dose distributions: A concept of equivalent uniform dose","volume":"24","author":"Niemierko","year":"1997","journal-title":"Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0150","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/0360-3016(94)00475-Z","article-title":"Radiation dose-response of human tumors","volume":"32","author":"Okunieff","year":"1995","journal-title":"Int J Radiat Oncol* Biol* Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0155","doi-asserted-by":"crossref","first-page":"366","DOI":"10.21037\/tlcr.2017.04.07","article-title":"The use of TCP based EUD to rank and compare lung radiotherapy plans: In-silico study to evaluate the correlation between TCP with physical quality indices","volume":"6","author":"Chaikh","year":"2017","journal-title":"Transl Lung Cancer Res"},{"key":"10.1016\/j.radonc.2022.09.021_b0160","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/0284186X.2017.1400177","article-title":"Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription","volume":"57","author":"Ureba","year":"2018","journal-title":"Acta Oncol (Madr)"},{"key":"10.1016\/j.radonc.2022.09.021_b0165","unstructured":"Dutch Association for Radiotherapy in Oncology. Landelijk Indicatie Protocol Protonen Therapie Longcarcinoom n.d. https:\/\/nvro.nl\/publicaties\/rapporten [accessed February 23, 2022]."},{"key":"10.1016\/j.radonc.2022.09.021_b0170","doi-asserted-by":"crossref","first-page":"605","DOI":"10.3109\/0284186X.2013.820341","article-title":"Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors","volume":"53","author":"Appelt","year":"2014","journal-title":"Acta Oncol (Madr)"},{"key":"10.1016\/j.radonc.2022.09.021_b0175","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.radonc.2015.08.010","article-title":"Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy","volume":"117","author":"Wijsman","year":"2015","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0180","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.radonc.2018.07.021","article-title":"External validation of an NTCP model for acute esophageal toxicity in locally advanced NSCLC patients treated with intensity-modulated (chemo-)radiotherapy","volume":"129","author":"Dankers","year":"2018","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0185","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.radonc.2019.09.005","article-title":"Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer","volume":"152","author":"Defraene","year":"2020","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0190","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ijrobp.2018.09.029","article-title":"Validation of Effective Dose as a Better Predictor of Radiation Pneumonitis Risk Than Mean Lung Dose: Secondary Analysis of a Randomized Trial","volume":"103","author":"Tucker","year":"2019","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0195","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.radonc.2020.03.003","article-title":"Lyman\u2013Kutcher\u2013Burman normal tissue complication probability modeling for radiation-induced esophagitis in non-small cell lung cancer patients receiving proton radiotherapy: LKB NTCP modeling for radiation-induced esophagitis in NSCLC patients receiving pr","volume":"146","author":"Wang","year":"2020","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0200","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.radonc.2020.04.046","article-title":"Deformable image registration uncertainty for inter-fractional dose accumulation of lung cancer proton therapy","volume":"147","author":"Nenoff","year":"2020","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.radonc.2022.09.021_b0205","doi-asserted-by":"crossref","DOI":"10.1088\/1361-6560\/abf8f5","article-title":"An approach for estimating dosimetric uncertainties in deformable dose accumulation in pencil beam scanning proton therapy delivered for lung cancer","author":"Amstutz","year":"2021","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.radonc.2022.09.021_b0210","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1088\/0031-9155\/56\/11\/006","article-title":"Modelling of the oxygen enhancement ratio for ion beam radiation therapy","volume":"56","author":"Wenzl","year":"2011","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.radonc.2022.09.021_b0215","doi-asserted-by":"crossref","first-page":"4502","DOI":"10.1118\/1.4730292","article-title":"A modified hypoxia-based TCP model to investigate the clinical outcome of stereotactic hypofractionated regimes for early stage non-small-cell lung cancer (NSCLC)","volume":"39","author":"Strigari","year":"2012","journal-title":"Med Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0220","doi-asserted-by":"crossref","unstructured":"Zegers CML, Hoebers FJP, Van Elmpt W, Bons JA, \u00d6llers MC, Troost EGC, et al. Evaluation of tumour hypoxia during radiotherapy using [ 18 F] HX4 PET imaging and blood biomarkers in patients with head and neck cancer. Eur J Nucl Med Mol Imaging n.d. https:\/\/doi.org\/10.1007\/s00259-016-3429-y.","DOI":"10.1007\/s00259-016-3429-y"},{"key":"10.1016\/j.radonc.2022.09.021_b0225","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/0360-3016(95)00170-4","article-title":"Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography","volume":"33","author":"Koh","year":"1995","journal-title":"Int J Radiat Oncol* Biol* Phys"},{"key":"10.1016\/j.radonc.2022.09.021_b0230","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.radonc.2016.09.011","article-title":"An evaluation of rescanning technique for liver tumour treatments using a commercial PBS proton therapy system","volume":"121","author":"Zhang","year":"2016","journal-title":"Radiother Oncol"}],"container-title":["Radiotherapy and Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814022044917?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814022044917?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:24:50Z","timestamp":1759123490000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167814022044917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":46,"alternative-id":["S0167814022044917"],"URL":"https:\/\/doi.org\/10.1016\/j.radonc.2022.09.021","relation":{},"ISSN":["0167-8140"],"issn-type":[{"value":"0167-8140","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer","name":"articletitle","label":"Article Title"},{"value":"Radiotherapy and Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.radonc.2022.09.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}