Development and Validation of a Computed Tomography-Based Radiomics Nomogram for the Preoperative Prediction of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

Abstract

Rationale and objectives: This study aims to develop and validate a computed tomography (CT)-based radiomics nomogram for pre-operatively predicting central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) and explore the underlying biological basis by using RNA sequencing data.

Methods: This study trained 452 PTMC patients across two hospitals from January 2012 to December 2020. The sets were randomly divided into the training (n = 339), internal test (n = 86), external test (n = 27) sets. Radiomics features were extracted from primary lesion's pre-operative CT images for each patient. After screening for features, five algorithms such as K-nearest neighbor, logistics regression, linear-support vector machine (SVM), Gaussian SVM, and polynomial SVM were used to establish the radiomics models. The performance of these five algorithms was evaluated and compared directly to radiologist's interpretation (CT-reported lymph node status). The radiomics signature score (Rad-score) was generated using a linear combination of the selected features. By combining the clinical risk factors and Rad score, a radiomics nomogram was established and compared with Rad-score and clinical model. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve analysis (DCA). The potential biological basis of nomogram was revealed by performing genetic analysis based on the RNA sequencing data.

Results: A total of 25 radiomic features were ultimately selected to train the machine learning models, and the five machine learning models outperformed the radiologists' interpretation by achieving area under the ROC curves (AUCs) ranging from 0.606 to 0.730 in the internal test set. By incorporating the Rad score and clinical risk factors (sex, age, tumor-diameter, and CT-reported lymph node status), this nomogram achieved AUCs of 0.800 and 0.803 in the internal and external test set, which were higher than that of the Rad-score and clinical model, respectively. Calibration curves and DCA also showed that the nomogram had good performance. As for the biological basis exploration, in patients predicted by nomogram to be PTC patients with CLMN, 109 genes were dysregulated, and some of them were associated with pathways and biological processes such as tumor angiogenesis.

Conclusion: This radiomics nomogram successfully identified CLNM on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists and had the potential to be integrated into clinical decision making as a non-invasive pre-operative tool.

Keywords: Central lymph node metastasis; Nomogram; Papillary thyroid microcarcinoma; Radiomics; Transcriptomics.