A Contrast‐Enhanced Ultrasound Cine‐Based Deep Learning Model for Predicting the Response of Advanced Hepatocellular Carcinoma to Hepatic Arterial Infusion Chemotherapy Combined With Systemic Therapies

ABSTRACT Recently, a hepatic arterial infusion chemotherapy (HAIC)‐associated combination therapeutic regimen, comprising HAIC and systemic therapies (molecular targeted therapy plus immunotherapy), referred to as HAIC combination therapy, has demonstrated promising anticancer effects. Identifying individuals who may potentially benefit from HAIC combination therapy could contribute to improved treatment decision‐making for patients with advanced hepatocellular carcinoma (HCC). This dual‐center study was a retrospective analysis of prospectively collected data with advanced HCC patients who underwent HAIC combination therapy and pretreatment contrast‐enhanced ultrasound (CEUS) evaluations from March 2019 to March 2023. Two deep learning models, AE‐3DNet and 3DNet, along with a time‐intensity curve‐based model, were developed for predicting therapeutic responses from pretreatment CEUS cine images. Diagnostic metrics, including the area under the receiver‐operating‐characteristic curve (AUC), were calculated to compare the performance of the models. Survival analysis was used to assess the relationship between predicted responses and prognostic outcomes. The model of AE‐3DNet was constructed on the top of 3DNet, with innovative incorporation of spatiotemporal attention modules to enhance the capacity for dynamic feature extraction. 326 patients were included, 243 of whom formed the internal validation cohort, which was utilized for model development and fivefold cross‐validation, while the rest formed the external validation cohort. Objective response (OR) or non‐objective response (non‐OR) were observed in 63% (206/326) and 37% (120/326) of the participants, respectively. Among the three efficacy prediction models assessed, AE‐3DNet performed superiorly with AUC values of 0.84 and 0.85 in the internal and external validation cohorts, respectively. AE‐3DNet's predicted response survival curves closely resembled actual clinical outcomes. The deep learning model of AE‐3DNet developed based on pretreatment CEUS cine performed satisfactorily in predicting the responses of advanced HCC to HAIC combination therapy, which may serve as a promising tool for guiding combined therapy and individualized treatment strategies. Trial Registration: NCT02973685.