{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:02Z","timestamp":1791348722992,"version":"4.3.1"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cisplatin (CDDP) is a key chemotherapeutic agent used to treat head and neck cancer. Improved survival rates have increased concerns about CDDP\u2010induced ototoxicity, as this toxicity significantly impacts survivors' quality of life. However, the dose\u2010dependent and age\u2010related patterns of CDDP\u2010induced ototoxicity remain incompletely defined. Therefore, in this study, we aimed to characterize CDDP\u2010induced ototoxicity by tracking longitudinal hearing data and evaluating the associated factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed a cohort of 316 patients with head and neck cancer who received CDDP\u2010based chemotherapy at a tertiary cancer center between January 2009 and June 2023. Hearing function was longitudinally assessed using pure\u2010tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAE) across the cumulative CDDP dose. Multivariate logistic regression analyses were performed to identify the factors associated with ototoxicity, including the cumulative dose, age, radiotherapy, and the primary tumor site.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, older patients exhibited substantially impaired high\u2010frequency hearing compared with younger patients. Across all age groups, hearing deteriorated in a dose\u2013dependent manner following CDDP exposure. However, despite smaller apparent longitudinal threshold shifts, older patients developed clinically relevant PTA\u2010defined ototoxicity at lower cumulative CDDP doses than younger patients, reflecting limited auditory reserve. Contrastingly, larger threshold shifts observed in younger patients reflected greater measurable dynamic range from preserved baseline hearing rather than an increased vulnerability. DPOAE changes were attenuated in older patients, suggesting that DPOAE had reduced sensitivity for detecting CDDP\u2010induced ototoxicity in the presence of pre\u2010existing cochlear damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CDDP\u2010induced ototoxicity shows distinct age\u2010dependent patterns, with older patients experiencing clinically significant hearing impairment at lower cumulative doses despite smaller longitudinal changes. These findings highlight the need for age\u2010adapted monitoring strategies and cumulative dose\u2010conscious treatment planning to preserve auditory function in cancer survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72323","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:48:56Z","timestamp":1791348536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010Dependent Patterns of Cisplatin\u2010Induced Ototoxicity in Head and Neck Cancer: A Longitudinal Audiologic Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3287-7857","authenticated-orcid":false,"given":"C.","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"Department of Early Clinical Development, Graduate School of Medicine, Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki\u2010CONNECT) Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-0165","authenticated-orcid":false,"given":"Y.","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-7090","authenticated-orcid":false,"given":"M.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Behavioral Statistics, Graduate School of Human Sciences The University of Osaka  Osaka Japan"},{"name":"RIKEN Center for Advanced Intelligence Project  Tokyo Japan"},{"name":"Data Science and AI Innovation Research Promotion Center Shiga University  Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8924-0710","authenticated-orcid":false,"given":"N.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Kanazawa Medical University  Kahoku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8904-8825","authenticated-orcid":false,"given":"S.","family":"Hiraoka","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Image\u2010Applied Therapy Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5412-5843","authenticated-orcid":false,"given":"R.","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Image\u2010Applied Therapy Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-3317","authenticated-orcid":false,"given":"S.","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Biomedical Statistics and Bioinformatics Kyoto University Graduate School of Medicine Kyoto  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-5461","authenticated-orcid":false,"given":"K.","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"Department of Head and Neck Oncology and Innovative Treatment, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2023.1102236","article-title":"Descriptive Epidemiology of the Head and Neck Cancers in Old Patients","volume":"13","author":"Gatta G.","year":"2023","journal-title":"Frontiers in Oncology"},{"issue":"4","key":"e_1_2_11_3_1","first-page":"271","article-title":"Cancer Treatment and Survivorship Statistics, 2016","volume":"66","author":"Miller K. D.","year":"2016","journal-title":"CA: a Cancer Journal for Clinicians"},{"issue":"3","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/toxics3030268","article-title":"Cisplatin\u2010Induced Ototoxicity: Effects, Mechanisms and Protection Strategies","volume":"3","author":"Callejo A.","year":"2015","journal-title":"Toxics"},{"issue":"1","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11764-022-01314-9","article-title":"The Long\u2010Term Impacts of Hearing Loss, Tinnitus and Poor Balance on the Quality of Life of People Living With and Beyond Cancer After Platinum\u2010Based Chemotherapy: A Literature Review","volume":"17","author":"Phillips O. R.","year":"2023","journal-title":"Journal of Cancer Survivorship: Research & Practice"},{"issue":"10452","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia Prevention, Intervention, and Care: 2024 Report of the Lancet Standing Commission","volume":"404","author":"Livingston G.","year":"2024","journal-title":"Lancet"},{"issue":"1","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13020-023-00825-6","article-title":"Age\u2010Related Hearing Loss and Its Potential Drug Candidates: A Systematic Review","volume":"18","author":"Hu S.","year":"2023","journal-title":"Chinese Medicine"},{"issue":"8","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tips.2013.05.006","article-title":"Understanding Platinum\u2010Induced Ototoxicity","volume":"34","author":"Langer T.","year":"2013","journal-title":"Trends in Pharmacological Sciences"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/1809394","article-title":"Cisplatin\u2010Associated Ototoxicity: A Review for the Health Professional","volume":"2016","author":"Paken J.","year":"2016","journal-title":"Journal of Toxicology"},{"issue":"10314","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1016\/S0140-6736(21)01789-X","article-title":"Evaluation of Geriatric Assessment and Management on the Toxic Effects of Cancer Treatment (GAP70+): A Cluster\u2010Randomised Study","volume":"398","author":"Mohile S. 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A.","year":"2009","journal-title":"Journal of the Acoustical Society of America"},{"issue":"2","key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3766\/jaaa.26.2.3","article-title":"High\u2010Frequency Audibility: The Effects of Audiometric Configuration, Stimulus Type, and Device","volume":"26","author":"Kimlinger C.","year":"2015","journal-title":"Journal of the American Academy of Audiology"},{"issue":"3","key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.ijrobp.2009.04.096","article-title":"Radiation Therapy and Hearing Loss","volume":"76","author":"Bhandare N.","year":"2010","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"12","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16122228","article-title":"Audiological Outcomes of Weekly vs. Triweekly Cisplatin in Head and Neck Cancer With Cochlear\u2010Sparing Intensity\u2010Modulated Radiation Therapy","volume":"16","author":"Gamez M. E.","year":"2024","journal-title":"Cancers"},{"issue":"12","key":"e_1_2_11_27_1","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1007\/s00405-024-08880-x","article-title":"Treatment\u2010Related Hearing Loss in Weekly Versus Triweekly Cisplatin Chemoradiation for Head and Neck Cancer","volume":"281","author":"Burger A. V. M.","year":"2024","journal-title":"European Archives of Oto\u2010Rhino\u2010Laryngology"},{"issue":"20","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.196230","article-title":"Lower, More Frequent Cisplatin Dosing Minimizes Hearing Loss in Head and Neck Cancer","volume":"10","author":"Fernandez K. A.","year":"2025","journal-title":"JCI Insight"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72323","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72323","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:49:09Z","timestamp":1791348549000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cam4.72323"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72323","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72323"}}