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Med. Biol."],"published-print":{"date-parts":[[2025,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\n                  <jats:italic>Objective<\/jats:italic>. Due to higher dose conformality to the target, proton radiotherapy for cancer has received rapidly-growing interest. However, uncertainties in the <jats:italic>in vivo<\/jats:italic> proton range and methods to reduce them remain active areas of research. Based on 20 patients with head-and-neck cancer, this study aims to quantify the benefits of proton range uncertainty reductions in terms of the resulting improvements in quality-adjusted life expectancy (QALE). <jats:italic>Approach<\/jats:italic>. For each patient, two different proton therapy treatment plans were created, which assumed a current clinical range uncertainty of approximately 3.5% (IMPT<jats:sub>3.5%<\/jats:sub>) and a potentially achievable range uncertainty of 1.0% (IMPT<jats:sub>1%<\/jats:sub>). A Markov model considering the probability of tumor control and the development of xerostomia, larynx edema, secondary cancer, and\/or metastases as well as death from primary cancer, secondary cancer, metastases, or unrelated causes was constructed, and for every patient and treatment plan, 10\u2009000 simulations of the patient\u2019s entire lifetime from the time of treatment until death were performed. <jats:italic>Main results.<\/jats:italic> A 3.5%\u20131% range uncertainty reduction increased QALE by up to 0.4 quality-adjusted life years (QALYs) in the nominal and up to 0.6 QALY in the worst-case scenario, equivalent to 4.8 months and 7.2 months of life in perfect health. This was largely the result of a reduction in healthy tissue toxicity rates, which were reduced by up to 8.5 percentage points (pp) and 10.0 pp in the nominal and worst-case scenario, respectively. <jats:italic>Significance<\/jats:italic>. The benefits of a 3.5%\u20131% range uncertainty reduction in 20 patients with head-and-neck cancer were quantified in terms of the associated improvement in QALE. The highest QALE improvements were observed in patients in the top quartile of youngest patients at the time of treatment, due to the longer potential lifespan over which prevented healthy tissue toxicities would have impacted the patients\u2019 quality of life.<\/jats:p>","DOI":"10.1088\/1361-6560\/add07d","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T22:57:38Z","timestamp":1745535458000},"page":"105001","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Range uncertainty reductions in proton therapy and resulting improvements in quality-adjusted life expectancy (QALE) for head-and-neck cancer patients"],"prefix":"10.1088","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9854-0011","authenticated-orcid":true,"given":"Sebastian","family":"Tattenberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peilin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Mulhem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoda","family":"Cong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Thome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3961-5470","authenticated-orcid":true,"given":"Cornelia","family":"Hoehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanfeng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"pmbadd07dbib1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15620\/cdc:132418","article-title":"United States life tables, 2021","volume":"72","author":"Arias","year":"2023","journal-title":"Natl Vital Stat. 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