{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:51:22Z","timestamp":1782982282553,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: We aimed to compare the salivary gland volume changes following intensity-modulated radiation therapy (IMRT) alone versus IMRT\/intensity-modulated proton therapy (IMPT) combination in oropharyngeal cancer (OPC). Methods: We retrospectively reviewed 78 OPC patients who underwent definitive RT with ipsilateral neck irradiation. RT techniques were either IMRT alone or IMRT\/IMPT combination. Salivary gland volumes over time in relation to dry mouth symptom were evaluated. Results: Patients\u2019 characteristics were well balanced between groups. The mean dose to the ipsilateral parotid gland (PG) was significantly lower in IMRT alone than in IMRT\/IMPT combination, while those to the contralateral PG and submandibular glands (SMGs) were significantly higher in IMRT alone. The volume ratio of ipsilateral PG showed an initial sharp decline, reaching 0.74, and stabilized thereafter. The ipsilateral SMG showed a continuous decline until 24 months and reached approximately 0.47 by 48 months. The contralateral PG\/SMG showed initial decline and subsequent recovery to the initial volume by 48 months. There were no significant differences in salivary gland volume changes between groups. Within 6 months, 60.3% of patients experienced dry mouth symptom, and the dry mouth incidence decreased to 41.0% in 12 months and remained stable thereafter. There were no significant differences in dry mouth symptom between groups. The volume reduction in the ipsilateral salivary glands was greater in patients with dry mouth symptom. Conclusions: No significant differences in salivary gland volume changes and dry mouth symptom were apparent between groups. The critical factor in salivary gland volume change was the delivered dose to the salivary glands, not the RT techniques.<\/jats:p>","DOI":"10.3390\/cancers17030554","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T09:54:38Z","timestamp":1738835678000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Salivary Gland Volume Changes and Dry Mouth Symptom Following Definitive Radiation Therapy in Oropharyngeal Cancer Patients\u2014A Comparison of Two Different Approaches: Intensity-Modulated Radiation Therapy Versus Intensity-Modulated Radiation Therapy\/Intensity-Modulated Proton Therapy Combination"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-4599","authenticated-orcid":false,"given":"Seung Gyu","family":"Park","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-8472","authenticated-orcid":false,"given":"Yong Chan","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-5519","authenticated-orcid":false,"given":"Dongryul","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-997X","authenticated-orcid":false,"given":"Kyungmi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Gyu","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Man","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyeol","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2962-7207","authenticated-orcid":false,"given":"Euncheol","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-1623","authenticated-orcid":false,"given":"Han Gyul","family":"Yoon","sequence":"additional","affiliation":[{"name":"Kim Jaechul Graduate School of Artificial Intelligence, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barsouk, A., Aluru, J.S., Rawla, P., Saginala, K., and Barsouk, A. (2023). Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med. Sci., 11.","DOI":"10.3390\/medsci11020042"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s10552-019-01185-z","article-title":"Treatment trends in head and neck cancer: Surveillance, Epidemiology, and End Results (SEER) Patterns of Care analysis","volume":"30","author":"Schlichting","year":"2019","journal-title":"Cancer Causes Control"},{"key":"ref_3","first-page":"95","article-title":"Salivary Gland Hypofunction and Xerostomia in Head and Neck Radiation Patients","volume":"53","author":"Jensen","year":"2019","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00520-010-0827-8","article-title":"A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Preva-lence, severity and impact on quality of life","volume":"18","author":"Jensen","year":"2010","journal-title":"Support. Care Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1080\/0284186X.2022.2110384","article-title":"Volumetric changes of the parotid gland during IMRT based on mid-treatment imaging: Implications for parotid stem cell sparing strategies in head and neck cancer","volume":"61","author":"Gjini","year":"2022","journal-title":"Acta Oncol."},{"key":"ref_6","first-page":"42","article-title":"Radiation-induced Parotid Gland Changes in Oral Cancer Patients: Correlation Between Parotid Volume and Saliva Production","volume":"40","author":"Teshima","year":"2009","journal-title":"Ultrasound Med. Biol."},{"key":"ref_7","first-page":"3239","article-title":"Changes in the Submandibular Gland in Patients with Head and Neck Cancer After Radiation Therapy: A Preliminary Study","volume":"37","author":"Uchiyama","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"521","DOI":"10.52547\/ijrr.19.3.521","article-title":"Structural evaluation of Parotid gland in post radiotherapy oral cancer patients: A prospective study","volume":"19","author":"Hao","year":"2021","journal-title":"Int. J. Radiat. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e416","DOI":"10.1016\/j.ijrobp.2021.07.1193","article-title":"Proton Therapy Specific Salivary Gland Volume Changes After Head and Neck Radiotherapy","volume":"111","author":"Walters","year":"2021","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ijrobp.2018.12.055","article-title":"A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oro-pharyngeal Cancer","volume":"104","author":"Rwigema","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1111\/cas.14115","article-title":"Early clinical outcomes of helical tomotherapy\/intensity-modulated proton therapy combination in naso-pharynx cancer","volume":"110","author":"Park","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yoon, H.G., Ahn, Y.C., Oh, D., Noh, J.M., Park, S.G., Nam, H., Ju, S.G., Kwon, D., and Park, S. (2021). Early Clinical Outcomes of Intensity Modulated Radiation Therapy\/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients. Cancers, 13.","DOI":"10.20944\/preprints202102.0002.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3322\/caac.21389","article-title":"Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual","volume":"67","author":"Lydiatt","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4143\/crt.2020.572","article-title":"Development of a Tongue Immobilization Device Using a 3D Printer for IMRT of Nasopharyngeal Cancer Patients","volume":"53","author":"Ju","year":"2020","journal-title":"Cancer Res. Treat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4143\/crt.2018.240","article-title":"Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients","volume":"51","author":"Cho","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1118\/1.3584198","article-title":"Dynamic tomotherapy delivery","volume":"38","author":"Chen","year":"2011","journal-title":"Med. Phys."},{"key":"ref_18","unstructured":"U.S. Department of Health and Human Services, N.I.o.H., and National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ctrv.2017.07.003","article-title":"Treatment of late sequelae after radiotherapy for head and neck cancer","volume":"59","author":"Strojan","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1034\/j.1601-0825.2002.02838.x","article-title":"The enigmatic mechanism of irradiation-induced damage to the major salivary glands","volume":"8","author":"Nagler","year":"2002","journal-title":"Oral Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1200\/JCO.2007.11.5501","article-title":"Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early stage nasopharyngeal carcinoma patients","volume":"25","author":"Kam","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.ijrobp.2007.10.063","article-title":"Local anatomic changes in parotid and submandibular glands during radiotherapy for oro-pharynx cancer and correlation with dose, studied in detail with nonrigid registration","volume":"70","author":"Hoogeman","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20130363","DOI":"10.1259\/bjr.20130363","article-title":"Pattern and predictors of volumetric change of parotid glands during intensity modulated radiother-apy","volume":"86","author":"Sanguineti","year":"2013","journal-title":"Br. J. Radiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/acm2.12327","article-title":"Parotid gland radiation dose-xerostomia relationships based on actual delivered dose for nasopharyngeal carcinoma","volume":"19","author":"Lou","year":"2018","journal-title":"J. Appl. Clin. Med Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1259\/bjr\/30087983","article-title":"Post-radiotherapy morphological changes of parotid gland are dose- and radiotherapy tech-nique-dependent","volume":"84","author":"Ying","year":"2011","journal-title":"Br. J. Radiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/jrr\/rrad087","article-title":"Long-term outcomes of stimulated salivary flow and xerostomia after definitive intensity-modulated radiation therapy for patients with head and neck cancerdagger","volume":"65","author":"Hiraoka","year":"2024","journal-title":"J. Radiat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.ijrobp.2006.09.021","article-title":"The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy","volume":"67","author":"Li","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13014-015-0371-2","article-title":"Prospective longitudinal assessment of parotid gland function using dynamic quantitative pertechnate scintigraphy and estimation of dose\u2013response relationship of parotid-sparing radiotherapy in head-neck cancers","volume":"10","author":"Gupta","year":"2015","journal-title":"Radiat. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/1748-717X-6-125","article-title":"Parotid gland-recovery after radiotherapy in the head and neck region\u201436 months follow-up of a prospective clinical study","volume":"6","author":"Hey","year":"2011","journal-title":"Radiat. Oncol."},{"key":"ref_30","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":"2021","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1053\/j.seminoncol.2019.07.002","article-title":"Modern radiotherapy for head and neck cancer","volume":"46","author":"Alterio","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1470-2045(10)70290-4","article-title":"Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): A phase 3 multicentre randomised controlled trial","volume":"12","author":"Nutting","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhou, J., Wang, L., Qiu, T., Gao, H., Wang, L., Huang, S., He, X., and Wu, L. (2024). Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12391-7"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.radonc.2011.05.028","article-title":"Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer","volume":"101","author":"Simone","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21593\/kjhno\/2021.37.1.1","article-title":"Proton Therapy for Head and Neck Cancer: Current Clinical Applications and Future Direction","volume":"37","author":"Oh","year":"2021","journal-title":"Korean Soc. Head Neck Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/pro6.1149","article-title":"A review of proton therapy\u2014Current status and future directions","volume":"6","author":"Mohan","year":"2022","journal-title":"Precis. Radiat. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/rpd\/ncp005","article-title":"International Commission on Radiation Units and Measurements Report 78: Prescribing, Recording and Reporting Proton-beam Therapy","volume":"133","author":"Newhauser","year":"2009","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1088\/0031-9155\/53\/6\/016","article-title":"Comparison between the lateral penumbra of a collimated double-scattered beam and uncollimated scanning beam in proton radiotherapy","volume":"53","author":"Safai","year":"2008","journal-title":"Phys. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.radonc.2015.12.008","article-title":"Proton beam radiation therapy results in significantly reduced toxicity compared with intensi-ty-modulated radiation therapy for head and neck tumors that require ipsilateral radiation","volume":"118","author":"Romesser","year":"2016","journal-title":"Radiother. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:28:12Z","timestamp":1760027292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cancers17030554"],"URL":"https:\/\/doi.org\/10.3390\/cancers17030554","relation":{"is-referenced-by":[{"id-type":"doi","id":"10.1007\/s12663-025-02915-4","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}