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Markov models allowing for the simulation of the patient's entire lifetime post\u2010treatment and the determination of quality\u2010adjusted life expectancy (QALE) have been developed but generally disregard important considerations such as additional treatments received and second primary malignancies (SPMs). Clinical validation also largely remains outstanding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aims to expand and clinically validate a Markov model focusing on head\u2010and\u2010neck cancer patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Markov model considering tumor control, healthy tissue toxicities, distant metastases, radiation\u2010associated secondary cancer, and death from various causes was expanded to further include additional treatments received, SPMs, and the patient's smoking history. For each of 148 head\u2010and\u2010neck cancer patients, 437,000 simulations of the patient's entire lifetime post\u2010treatment were performed and compared to the patient's clinically\u2010documented outcomes (wherever available).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>94.4% of simulations exhibited locoregional control, compared to 89.9% of patients in clinical reality. Simulated death with locoregional failure was 4.9%, compared to 5.4% in real life. Patients developed and died with distant metastases in 8.0% of simulations, while 10.8% of patients developed distant metastases in real life and 5.7% of patients passed away with distant disease. The simulated second primary cancer rate was 13.5%. Patients exhibited at least one healthy tissue toxicity in 43.8% of simulations, and simulated life expectancy and QALE were 76.5\u00a0\u00b1\u00a011.6 years and 74.3\u00a0\u00b1\u00a011.0 quality\u2010adjusted life years (QALYs), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Agreement between simulation results and available clinically\u2010documented outcomes was generally excellent, enabling the evaluation of prospective clinical outcomes and comparisons between different patient populations along with variable treatment combinations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70696","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:30:41Z","timestamp":1791307841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expansion and clinical validation of Markov model\u2010based quality\u2010adjusted life expectancy (QALE) simulations for head\u2010and\u2010neck cancer radiotherapy patients"],"prefix":"10.1002","volume":"53","author":[{"given":"Sebastian","family":"Tattenberg","sequence":"first","affiliation":[{"name":"INSA\u2010Lyon, Universite Claude Bernard Lyon 1, CNRS, Inserm CREATIS UMR 5220, U1294  Lyon France"},{"name":"Life Sciences Division  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Allignet","sequence":"additional","affiliation":[{"name":"INSA\u2010Lyon, Universite Claude Bernard Lyon 1, CNRS, Inserm CREATIS UMR 5220, U1294  Lyon France"},{"name":"Department of Radiation Oncology Centre L\u00e9on B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Beaumont University Hospital \u2010 Corewell Health  Royal Oak Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Hoehr","sequence":"additional","affiliation":[{"name":"Life Sciences Division  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Beaumont University Hospital \u2010 Corewell Health  Royal Oak Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Beuf","sequence":"additional","affiliation":[{"name":"INSA\u2010Lyon, Universite Claude Bernard Lyon 1, CNRS, Inserm CREATIS UMR 5220, U1294  Lyon 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