{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:51Z","timestamp":1791474711056,"version":"4.3.4"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"\n Importance<\/jats:title>\n \n Older age at diagnosis is associated with worse outcomes in papillary thyroid carcinoma (PTC). The current American Joint Committee on Cancer tumor-node-metastasis staging system incorporates an age of 55 years or older as staging criteria.\n TERT<\/jats:italic>\n promoter variants are also associated with aggressive disease.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the interplay between age,\n TERT<\/jats:italic>\n promoter variants, and survival outcomes in PTC.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This multi-institutional retrospective cohort study was conducted from 1993 to 2020 at 3 academic centers in the US, with integration of publicly available cohorts from The Cancer Genome Atlas (TCGA) and American Association of Cancer Research\u2019s Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE). The cohort included 169 patients with PTC from 3 US academic centers, who were integrated with TCGA and AACR GENIE, yielding a combined analytic population of 1555 patients with PTC. The association between age and\n TERT<\/jats:italic>\n was examined across all patients. Within the multi-institutional cohort with long-term follow-up (n\u2009=\u2009169), the association between\n TERT<\/jats:italic>\n and survival was further examined.\n <\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Age at diagnosis and\n TERT<\/jats:italic>\n promoter status.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was disease-specific survival (DSS), and the secondary outcome was progression-free survival (PFS).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Across all cohorts (N\u2009=\u20091555; 966 female individuals [62.1%] and 589 male individuals [37.9%]), the prevalence of\n TERT<\/jats:italic>\n promoter variants increased progressively with age (\n r<\/jats:italic>\n \u2009=\u20090.59; 95% CI, 0.54-0.63), being rare in patients younger than 30 years (&amp;lt;2%) and reaching 32% to 70% in those older than 65 years. For survival analyses, 169 patients were included (median follow-up, 13.7 years; 95% CI, 10.4-15.9 years). Among patients younger than 55 years without a\n TERT<\/jats:italic>\n promoter variant, 10-year DSS was 100% and 10-year PFS was 83%. Among those 55 years or older, 10-year DSS was 91% for\n TERT<\/jats:italic>\n wild-type tumors and 51% for\n TERT<\/jats:italic>\n -variant tumors (91% vs 51%, respectively; difference, 40%; 95% CI, 4-68). A similar trend was observed for PFS (10-year PFS of 75% for\n TERT<\/jats:italic>\n wild-type vs 23% for\n TERT<\/jats:italic>\n variant; difference, 52%; 95% CI, 9-82). In multivariable analysis,\n TERT<\/jats:italic>\n promoter variants remained independently associated with worse DSS after adjustment for age and pathologic tumor, node, and metastasis categories.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n The findings of this cohort study suggest that the high prevalence of\n TERT<\/jats:italic>\n promoter variants in older patients largely explains the association between age and worse prognosis in PTC.\n TERT<\/jats:italic>\n promoter status offers more biologically grounded prognostic information than age and may improve risk stratification.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoto.2026.2273","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:01:08Z","timestamp":1787238068000},"page":"952","source":"Crossref","is-referenced-by-count":0,"title":["TERT<\/i>\n Promoter Variants, Older Age, and Prognosis in Papillary Thyroid 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