Abstract
OBJECTIVE: To construct a multimodal ultrasound (US) radiomics model for predicting axillary lymph node metastasis (ALNM) in breast cancer and evaluated its application value in predicting ALNM and patient prognosis. METHODS: From March 2014 to December 2022, data from 682 breast cancer patients from four hospitals were collected, including preoperative grayscale US, color Doppler flow imaging (CDFI), contrast-enhanced ultrasound (CEUS) imaging data, and clinical information. Data from the First Medical Center of PLA General Hospital were used as the training and internal validation sets, while data from Peking University First Hospital, the Cancer Hospital of the Chinese Academy of Medical Sciences, and the Fourth Medical Center of PLA General Hospital were used as the external validation set. LASSO regression was employed to select radiomic features (RFs), while eight machine learning algorithms were utilized to construct radiomic models based on US, CDFI, and CEUS. The prediction efficiency of ALNM was assessed to identify the optimal model. In the meantime, Radscore was computed and integrated with immunoinflammatory markers to forecast Disease-Free Survival (DFS) in breast cancer patients. Follow-up methods included telephone outreach and in-person hospital visits. The analysis employed Cox regression to pinpoint prognostic factors, while clinical-imaging models were developed accordingly. The performance of the model was evaluated using the C-index, Receiver Operating Characteristic (ROC) curves, calibration curves, and Decision Curve Analysis (DCA). RESULTS: In the training cohort (n = 400), 40% of patients had ALNM, with a mean age of 55 ± 10 years. The US + CDFI + CEUS-based radiomics model achieved Area Under the Curves (AUCs) of 0.88, 0.81, and 0.77 for predicting N0 versus N+ (≥ 1) in the training, internal, and external validation sets, respectively, outperforming the US-only model (P < 0.05). For distinguishing N+ (1-2) from N+ (≥ 3), the model achieved AUCs of 0.89, 0.74, and 0.75. Combining radiomics scores with clinical immunoinflammatory markers (platelet count and neutrophil-to-lymphocyte ratio) yielded a clinical-radiomics model predicting disease-free survival (DFS), with C-indices of 0.80, 0.73, and 0.79 across the three cohorts. In the external validation cohort, the clinical-radiomics model achieved higher AUCs for predicting 2-, 3-, and 5-year DFS compared to the clinical model alone (2-year: 0.79 vs. 0.66; 3-year: 0.83 vs. 0.70; 5-year: 0.78 vs. 0.64; all P < 0.05). Calibration and decision curve analyses demonstrated good model agreement and clinical utility. CONCLUSION: The multimodal ultrasound radiomics model based on US, CDFI, and CEUS could effectively predict ALNM in breast cancer. Furthermore, the combined application of radiomics and immune inflammation markers might predict the DFS of breast cancer patients to some extent.