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A simple four-variable nomogram integrating age, ACR-TIRADS, BRAF V600E and Bethesda cytology for predicting occult
Bin Cao1, Gao Fei1, Si-Cong Zhou2
1Ultrasound Department, Fujian Province Second People's Hospital, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Background:
Predicting occult central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC) is important for individualized surgical planning and risk-stratified decision-making, particularly in younger patients. This study aimed to develop and internally validate a simple four-variable nomogram integrating age, American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), BRAF V600E status, and Bethesda cytology for preoperative prediction of occult CLNM in PTMC.
Methods:
We retrospectively analyzed 130 PTMC patients (≤10 mm on pre-operative ultrasound) who underwent thyroidectomy with central lymph node dissection (CLND) at a single Chinese tertiary center (March 2020-December 2022). A four-variable logistic-regression nomogram (Model E) was developed integrating age, ACR-TIRADS category, BRAF V600E mutation status (from fine-needle aspiration), and Bethesda cytological classification. Internal validation used 5-fold stratified cross-validation. Calibration was assessed by the Hosmer-Lemeshow test and calibration curves; clinical utility by decision curve analysis (DCA).
Results:
CLNM was confirmed in 73/130 patients (56.2%). The 5-fold cross-validated area under the receiver operating characteristic curve (AUC) was 0.686, with acceptable calibration (Brier score 0.215; Hosmer-Lemeshow P=0.43). DCA demonstrated positive net clinical benefit across threshold probabilities of 0.31-0.95. Pre-specified but exploratory subgroup analyses suggested higher apparent discrimination in patients younger than 45 years (n=60; bootstrap median AUC 0.760, 95% CI: 0.574-0.888) and in BRAF wild-type cases (n=35; 0.864, 95% CI: 0.705-0.977), although CIs were wide and overlapping. In this PTMC cohort, BRAF V600E was not independently associated with CLNM; an inverse point estimate was observed but did not reach statistical significance and should be regarded as exploratory.
Conclusions:
This simple, four-variable nomogram provides clinically useful pre-operative CLNM risk assessment in PTMC, particularly in younger and BRAF wild-type patients-subgroups in which preoperative risk stratification is most challenging. External multi-center validation is the necessary next step.
