Combined model integrating clinical, radiomics, BRAF V600E and ultrasound for differentiating between benign and malignant indeterminate cytology (Bethesda III) thyroid nodules: a bi-center retrospective study

The management of thyroid nodules diagnosed as Bethesda III by fine-needle aspiration presents certain challenges, and there is an urgent need for a non-invasive and accurate method for early identification of the benign or malignant nature of Bethesda III nodules. Our objective is to develop and validate a clinical-radiomics nomogram based on preoperative ultrasound (US) images and clinical features, for predicting the malignancy of thyroid nodules with indeterminate cytology (Bethesda III). Between June 2017 and June 2022, we conducted a retrospective study on 274 patients with surgically confirmed indeterminate cytology (Bethesda III) across two separate medical centers in Shanghai. The training and internal validation sets were comprised of 136 and 58 patients, respectively, all sourced from Shanghai's Sixth People's Hospital. To facilitate external test, a further 80 patients were selected from Tinglin Hospital. Utilizing preoperative US data, we obtained imaging markers for radiomic features. After feature selection, we developed a comprehensive diagnostic model to evaluate the predictive value for Bethesda III benign and malignant cases. The model's diagnostic accuracy, calibration, and clinical applicability were systematically assessed. The results showed that the prediction model, which integrated US radiomics, and clinical risk features, exhibited superior stability in distinguishing between benign and malignant indeterminate thyroid nodules (Bethesda III). In the external test set, the area under the curve (AUC) was 0.824 [95% confidence interval (CI): 0.718-0.929], and the accuracy, sensitivity, specificity, precision, and recall were 0.775, 0.731, 0.796, 0.633, and 0.731, respectively. An integrated model, utilizing US radiomics and clinical risk features, effectively discriminates between benign and malignant indeterminate thyroid nodules (Bethesda III), thereby minimizing the need for unnecessary diagnostic surgeries and subsequent complications.