{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:10:27Z","timestamp":1789153827106,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To review and evaluate treatments for radiation\u2010induced fibrosis (RIF) following head and neck cancer (HNC) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>\n                      Medline,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/Embase.com\">Embase.com<\/jats:ext-link>\n                      , Web of Science, and Cochrane Library.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Review Methods<\/jats:title>\n                    <jats:p>A systematic review was conducted on the management of HNC RIF using the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses (PRISMA) guidelines. Descriptive synthesis was conducted to summarize treatment efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After initial screening of 4078 titles and abstracts, 147 full\u2010text articles were reviewed, with eight meeting inclusion criteria. Pharmacological interventions included pentoxifylline\u2010tocopherol, pravastatin, amifostine, and topical superoxide dismutase (SOD). Pentoxifylline\u2010tocopherol, pravastatin, and amifostine demonstrated variable fibrosis improvement rates across studies. In one uncontrolled trial, 83% of patients receiving pentoxifylline\u2010tocopherol achieved \u226550% reduction in measured fibrotic surface area, and pravastatin reduced fibrosis thickness by \u226530% in 35.7% of patients. Procedural interventions included lipotransfer and microcurrent therapy, with lipotransfer associated with physical improvements in 97% of patients (n\u2009=\u200938) and microcurrent therapy enhancing cervical mobility in 92% of patients (n\u2009=\u200926).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Improvements in HNC fibrosis after current treatments ranged widely across studies; however, substantial heterogeneity in study design and outcome measurement limits definitive conclusions regarding comparative effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ohn.70436","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:47:56Z","timestamp":1789152476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Interventions for Radiation\u2010Induced Fibrosis in Head and Neck Cancer Patients: A Systematic Review"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0782-2602","authenticated-orcid":false,"given":"Pooja D.","family":"Reddy","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purva","family":"Rumde","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Helou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Klem","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"},{"name":"Health Sciences Library System, University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Spector","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marci L.","family":"Nilsen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Contrera","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"2","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.radonc.2004.08.021","article-title":"The radiation\u2010induced fibroatrophic process: therapeutic perspective via the antioxidant pathway","volume":"73","author":"Delanian S","year":"2004","journal-title":"Radiother Oncol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","DOI":"10.1177\/11795549211036898","article-title":"Radiation\u2010induced fibrosis in patients with head and neck cancer: a review of pathogenesis and clinical outcomes","volume":"16","author":"Ramia P","year":"2022","journal-title":"Clin Med Insights Oncol"},{"issue":"7","key":"e_1_2_7_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17071108","article-title":"Radiation\u2010induced fibrosis in head and neck cancer: challenges and future therapeutic strategies for vocal fold treatments","volume":"17","author":"Jimenez\u2010Socha M","year":"2025","journal-title":"Cancers"},{"issue":"10","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1002\/hed.25888","article-title":"Evaluation of the efficacy of lipotransfer to manage radiation\u2010induced fibrosis and volume defects in head and neck oncology","volume":"41","author":"Griffin MF","year":"2019","journal-title":"Head Neck"},{"issue":"2","key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ijrobp.2019.02.024","article-title":"Pravastatin reverses established radiation\u2010induced cutaneous and subcutaneous fibrosis in patients with head and neck cancer: results of the biology\u2010driven phase 2 clinical trial Pravacur","volume":"104","author":"Bourgier C","year":"2019","journal-title":"Int J Radiat Oncol Biol 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