{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:50:51Z","timestamp":1791615051557,"version":"4.3.4"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: We evaluated a hypothetical oracle strategy that assumes BRAFV600E status is known before fine-needle aspiration (FNA), although testing usually requires FNA-derived material. Methods: This retrospective simulation included 4944 nodules from 4560 patients with linked ultrasound and molecular records following FNA evaluation. The cohort was selected for cytology and molecular testing and enriched for BRAFV600E positivity (42.4%) and TI-RADS 4C nodules (66.7%). The predefined rule combined BRAFV600E-positive upgrading with one-level downgrading of negative TI-RADS 4A\/4B nodules. Outcomes were FNA-actionable classification changes and retention of originally FNA-actionable Bethesda V\/VI nodules. Pre-FNA prediction was evaluated with patient-grouped cross-validation and training-fold calibration. Results: Under the hypothetical assumption of pre-FNA knowledge of BRAFV600E status, the oracle strategy reduced FNA-actionable classifications from 3454 to 2954 (net reduction 500; 14.5%) while retaining 1843\/1920 Bethesda V\/VI nodules (96.0%). In the selected surgical subgroup (365\/4944), malignant-nodule retention was 189\/196 (96.4%; 95% CI, 92.8\u201398.6%), with uncertainty extending below the exploratory 95% reference. Among 97 reclassified Bethesda III\/IV nodules, only 2 had surgical pathology, and 1 was malignant. Patient-grouped random forest AUC was 0.693 (95% CI, 0.678\u20130.707). After calibration, a training-selected high-sensitivity threshold reduced classifications by 10.6%, with Bethesda V\/VI retention of 95.6% (95% CI, 94.7\u201396.5%). Conclusions: This selected-cohort oracle simulation suggests a theoretical reduction in FNA-actionable classifications. Prospective evaluation in an unselected pre-biopsy population is required before clinical use.<\/jats:p>","DOI":"10.3390\/diagnostics16193216","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:02:27Z","timestamp":1791194547000},"page":"3216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BRAFV600E-Informed TI-RADS Reclassification of Biopsy Eligibility in Thyroid Nodules: A Retrospective Oracle Decision\u2013Simulation Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiaojiao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Ultrasound, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehua","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Ultrasound, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Shanshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Ruyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xuejiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Wanlin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Mingyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-2007","authenticated-orcid":false,"given":"Yong","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-5018","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Ultrasound, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/jama.2023.26348","article-title":"Thyroid cancer: A review","volume":"331","author":"Boucai","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e230067","DOI":"10.1530\/ETJ-23-0067","article-title":"2023 European Thyroid Association clinical practice guidelines for thyroid nodule management","volume":"12","author":"Durante","year":"2023","journal-title":"Eur. 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