{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:39:00Z","timestamp":1790998740757,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Cancer Society","award":["11350\/2017-2"],"award-info":[{"award-number":["11350\/2017-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice. Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients. Shifts in mean dose to the SCR regions (Dmean,SCR) and other organs at risk and their estimated impact on normal tissue complication probability (NTCP) for side-effects were compared using Wilcoxon signed-rank test. A multicenter study was performed (eight institutions, three patients) to test the generalizability of SCS-RT using the Friedman test. Results: Using photons, Dmean,SCR was reduced with median 4.1\/3.5 Gy for ipsilateral\/contralateral (p &lt; 0.001). The largest reductions were when the SCR regions overlapped less with target volumes. Subsequently, NTCPs for xerostomia decreased (p &lt; 0.001). Using protons, Dmean,SCR was also reduced (2.2\/1.9 Gy for ipsilateral\/contralateral, p &lt; 0.002). Nevertheless, SCS-RT did not further decrease NTCPs for xerostomia (p &gt; 0.17). Target coverage and prevention of other side-effects were not compromised. However, increased mean oral cavity dose was observed in some patients. Lastly, in the multicenter study Dmean,SCR could be reduced by slightly adjusting the standard optimization. Contralateral Dmean,SCR reductions differed between centers (p = 0.01), which was attributed to differences in ST-RT plans. Conclusions: Stem cell sparing radiotherapy can be clinically introduced by making small adjustments to the optimization strategy and can reduce the risk of xerostomia.<\/jats:p>","DOI":"10.3390\/cancers16244283","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T09:13:38Z","timestamp":1734945218000},"page":"4283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Introduction of Stem Cell Sparing Radiotherapy to Reduce the Risk of Xerostomia in Patients with Head and Neck Cancer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-8997","authenticated-orcid":false,"given":"Maria I.","family":"van Rijn-Dekker","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-7975","authenticated-orcid":false,"given":"Arjen","family":"van der Schaaf","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne W.","family":"Nienhuis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette S.","family":"Arents-Huls","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Radiotherapiegroep, 6815 AD Arnhem, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel B.","family":"Ger","sequence":"additional","affiliation":[{"name":"Radiation Oncology and Molecular Radiation Sciences, John Hopkins Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Hamming-Vrieze","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J. P.","family":"Hoebers","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Reproduction, Maastricht University, 6229 ET Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-3038","authenticated-orcid":false,"given":"Mischa","family":"de Ridder","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Vigorito","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-8215","authenticated-orcid":false,"given":"Ellen M.","family":"Zwijnenburg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-372X","authenticated-orcid":false,"given":"Johannes A.","family":"Langendijk","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-1234","authenticated-orcid":false,"given":"Peter","family":"van Luijk","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel J. H. M.","family":"Steenbakkers","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i69","DOI":"10.1093\/jrr\/rrw047","article-title":"IMRT for head and neck cancer: Reducing xerostomia and dysphagia","volume":"57","author":"Wang","year":"2016","journal-title":"J. Radiat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.radonc.2021.03.036","article-title":"Intensity-modulated proton therapy for oropharyngeal cancer reduces rates of late xerostomia","volume":"160","author":"Cao","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.radonc.2021.01.024","article-title":"Comprehensive toxicity risk profiling in radiation therapy for head and neck cancer: A new concept for individually optimised treatment","volume":"157","author":"Hoebers","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Onjukka, E., Mercke, C., Bj\u00f6rgvinsson, E., Embring, A., Berglund, A., von D\u00f6beln, G.A., Friesland, S., Gagliardi, G., Helleday, C.L., and Sj\u00f6din, H. (2020). Modeling of Xerostomia After Radiotherapy for Head and Neck Cancer: A Registry Study. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01647"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109458","DOI":"10.1016\/j.radonc.2022.109458","article-title":"Validation of the 18F-FDG PET image biomarker model predicting late xerostomia after head and neck cancer radiotherapy","volume":"180","author":"Li","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_6","first-page":"305ra147","article-title":"Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer","volume":"7","author":"Pringle","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.ijrobp.2004.12.035","article-title":"Volume effects and region-dependent radiosensitivity of the parotid gland","volume":"62","author":"Konings","year":"2005","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.ijrobp.2009.03.039","article-title":"Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy","volume":"74","author":"Faber","year":"2009","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.ijrobp.2024.04.012","article-title":"Radiation-induced xerostomia is related to stem cell dose-dependent reduction of saliva production","volume":"120","author":"Stokman","year":"2024","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.ijrobp.2023.04.034","article-title":"Prediction of Radiation-Induced Parotid Gland\u2013Related Xerostomia in Patients With Head and Neck Cancer: Regeneration-Weighted Dose","volume":"117","author":"Schuit","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ijrobp.2021.09.023","article-title":"Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer: A Double-Blind Randomized Controlled Trial","volume":"112","author":"Steenbakkers","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.radonc.2022.05.001","article-title":"Prospective assessment of sparing the parotid ducts via MRI sialography for reducing patient reported xerostomia","volume":"172","author":"Fried","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1056\/NEJMsa035507","article-title":"Clinical Research to Clinical Practice\u2014Lost in Translation?","volume":"349","author":"Lenfant","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/QMH.0b013e31828bc21d","article-title":"Awareness of Evidence-Based Practices Alone Does Not Translate to Implementation","volume":"22","author":"Rangachari","year":"2013","journal-title":"Qual. Manag. Health Care"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kristensen, N., Nymann, C., and Konradsen, H. (2015). Implementing research results in clinical practice- the experiences of healthcare professionals. BMC Health Serv. Res., 16.","DOI":"10.1186\/s12913-016-1292-y"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.ijrobp.2008.01.012","article-title":"Beam Path Toxicities to Non-Target Structures During Intensity-Modulated Radiation Therapy for Head and Neck Cancer","volume":"72","author":"Rosenthal","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.radonc.2014.10.008","article-title":"Different treatment planning protocols can lead to large differences in organ at risk sparing","volume":"113","author":"Tol","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ijrobp.2019.07.005","article-title":"Targeted Intervention to Improve the Quality of Head and Neck Radiation Therapy Treatment Planning in the Netherlands: Short and Long-Term Impact","volume":"105","author":"Verbakel","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"354","DOI":"10.14338\/IJPT-20-00089.1","article-title":"National Protocol for Model-Based Selection for Proton Therapy in Head and Neck Cancer","volume":"8","author":"Langendijk","year":"2021","journal-title":"Int. J. Part. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.radonc.2021.04.012","article-title":"Development of advanced preselection tools to reduce redundant plan comparisons in model-based selection of head and neck cancer patients for proton therapy","volume":"160","author":"Tambas","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20190955","DOI":"10.1259\/bjr.20190955","article-title":"Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer","volume":"93","author":"Meijer","year":"2020","journal-title":"Br. J. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S1470-2045(17)30179-1","article-title":"Proton therapy for head and neck cancer: Expanding the therapeutic window","volume":"18","author":"Leeman","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.radonc.2020.07.056","article-title":"First experience with model-based selection of head and neck cancer patients for proton therapy","volume":"151","author":"Tambas","year":"2020","journal-title":"Radiother. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.radonc.2015.07.041","article-title":"CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines","volume":"117","author":"Brouwer","year":"2015","journal-title":"Radiother. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.ijrobp.2010.05.012","article-title":"Potential Benefits of Scanned Intensity-Modulated Proton Therapy Versus Advanced Photon Therapy With Regard to Sparing of the Salivary Glands in Oropharyngeal Cancer","volume":"79","author":"Lomax","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.radonc.2022.07.006","article-title":"Impact on xerostomia for nasopharyngeal carcinoma patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study","volume":"175","author":"Huang","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109670","DOI":"10.1016\/j.radonc.2023.109670","article-title":"Proton arc therapy increases the benefit of proton therapy for oropharyngeal cancer patients in the model based clinic","volume":"184","author":"Korevaar","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e313","DOI":"10.1016\/j.ijrobp.2011.05.005","article-title":"Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer","volume":"82","author":"Lomax","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3109\/0284186X.2013.831186","article-title":"The QUANTEC criteria for parotid gland dose and their efficacy to prevent moderate to severe patient-rated xerostomia","volume":"53","author":"Beetz","year":"2013","journal-title":"Acta Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ijrobp.2022.04.021","article-title":"In Reply to Kashid et al","volume":"113","author":"Steenbakkers","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.radonc.2014.08.020","article-title":"Direct use of multivariable normal tissue complication probability models in treatment plan optimisation for individualised head and neck cancer radiotherapy produces clinically acceptable treatment plans","volume":"112","author":"Kierkels","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.oraloncology.2018.08.018","article-title":"Revisiting the dose constraints for head and neck OARs in the current era of IMRT","volume":"86","author":"Brodin","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.radonc.2013.05.007","article-title":"Selection of patients for radiotherapy with protons aiming at reduction of side effects: The model-based approach","volume":"107","author":"Langendijk","year":"2013","journal-title":"Radiother. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.radonc.2017.01.012","article-title":"Cross-institutional knowledge-based planning (KBP) implementation and its performance comparison to Auto-Planning Engine (APE)","volume":"123","author":"Wu","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13014-018-1113-z","article-title":"Planning comparison of five automated treatment planning solutions for locally advanced head and neck cancer","volume":"13","author":"Krayenbuehl","year":"2018","journal-title":"Radiat. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.1088\/1361-6560\/aa71f8","article-title":"Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method","volume":"62","author":"McIntosh","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.ijrobp.2022.12.004","article-title":"Automated Robust Planning for IMPT in Oropharyngeal Cancer Patients Using Machine Learning","volume":"115","author":"Huiskes","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.ijrobp.2014.11.014","article-title":"Evaluation of a Knowledge-Based Planning Solution for Head and Neck Cancer","volume":"91","author":"Tol","year":"2015","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s13014-015-0542-1","article-title":"Can knowledge-based DVH predictions be used for automated, individualized quality assurance of radiotherapy treatment plans?","volume":"10","author":"Tol","year":"2015","journal-title":"Radiat. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s13014-015-0533-2","article-title":"Evaluation of an automated knowledge based treatment planning system for head and neck","volume":"10","author":"Krayenbuehl","year":"2015","journal-title":"Radiat. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/24\/4283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:58:40Z","timestamp":1760115520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/24\/4283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":40,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["cancers16244283"],"URL":"https:\/\/doi.org\/10.3390\/cancers16244283","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}