{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:30:37Z","timestamp":1790739037196,"version":"4.1.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Unlike patient age, which has been a well-established and routinely used primary biological prognostic factor in the risk stratification of papillary thyroid cancer (PTC), the prognostic value of patient sex remains controversial in this common endocrine malignant neoplasm.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To examine PTC-specific mortality risk of sex with respect to patient age and tumor genetics\u2014specifically the status of\n BRAF<\/jats:italic>\n V600E and\n TERT<\/jats:italic>\n promoter (\n TERT<\/jats:italic>\n p) mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This cohort study was conducted among patients with PTC with an overall median (IQR) follow-up time of 51.0 (26.4-109.1) months after initial treatment at 15 centers in 10 countries between 1979 and 2023. Data analysis was completed in December 2025 and examined aggregately for the association of PTC-specific mortality and patient sex with respect to patient age and\n BRAF<\/jats:italic>\n V600E and\n TERT<\/jats:italic>\n p mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measure<\/jats:title>\n Patient deaths specifically caused by PTC.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study included 4746 patients with PTC (median [IQR] age, 48 [37-59] years; 3612 women [76.1%]). Male patients, compared with female patients, demonstrated a higher overall PTC-specific mortality (3.7% [42 of 1134] vs 1.7% [60 of 3612];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). This male sex\u2013associated risk was observed only in patients harboring\n BRAF<\/jats:italic>\n V600E or\n TERT<\/jats:italic>\n p mutations, not wild-type genes. PTC-specific mortality particularly paralleled the occurrence and accumulation of dual\n BRAF<\/jats:italic>\n V600E and\n TERT<\/jats:italic>\n p mutations, which all exhibited a patient age-dependent rise, beginning to be prominent around age 45 years and markedly amplified by male sex. A male sex-age synergy index of 1.81 (95% CI, 1.02-3.16) and a male-to-female hazard ratio of 3.07 (95% CI, 1.35-6.97;\n P<\/jats:italic>\n \u2009=\u2009.007) after adjustment for clinicopathologic factors in mortality risk were observed in patients aged 45 years or older with dual mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n This cohort study reconciled previous controversies on the prognostic value of patient sex and establishes male sex as a cardinal mortality risk in PTC in a patient age- and tumor genetic-dependent manner, defining especially male patients aged 45 years and older with dual\n BRAF<\/jats:italic>\n V600E and\n TERT<\/jats:italic>\n p mutations as having the worst prognosis and supporting integration of patient sex into risk stratification of PTC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.35582","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:30:17Z","timestamp":1790695817000},"page":"e2635582","source":"Crossref","is-referenced-by-count":1,"title":["Sex and Mortality Among Patients with Papillary Thyroid Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Liufeng","family":"Wu","sequence":"first","affiliation":[{"name":"School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhuang","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 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