Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma by Integrating Multimodal Ultrasound and Clinical Data: A Multicenter Study
Authors: Jun Cheng, Yuanyuan Kong, Qing Huang, Xiaotong Tan, Licong Dong, Yulong Han, Wufeng Xue, Ruobing Huang, +4 more
Background: Microvascular invasion (MVI) predicts recurrence and survival in hepatocellular carcinoma (HCC) but requires postoperative histopathology for diagnosis. We developed and validated a model integrating multimodal ultrasound and clinical data for preoperative MVI prediction. Methods: This multicenter study included 489 patients with HCC from eight centers. All patients had B-mode ultrasound (BUS), color Doppler flow imaging (CDFI), dynamic contrast-enhanced ultrasound (DCE-US), and clinical information. Data from seven centers (n = 421) were used for model development with five-fold cross-validation; data from the remaining center (n = 68) formed an independent external validation cohort. The proposed multimodal information fusion network used modality-specific encoders, a hemodynamic temporal change module for bidirectional DCE-US perfusion changes, and a representation consistency learning module to align heterogeneous ultrasound representations before Transformer-based fusion. Results: In external validation, DCE-US achieved the highest single-modality area under the receiver operating characteristic curve (AUC; 0.8545+/-0.0198), versus clinical information (0.6715+/-0.0156), CDFI (0.6435+/-0.0344), and BUS (0.6087+/-0.0417). Pixel-difference sampling and the proposed temporal module outperformed alternative sampling and video representation methods. The full model achieved the best performance, with an AUC of 0.8953+/-0.0180, accuracy of 81.18%+/-2.83%, sensitivity of 86.40%+/-6.69%, and specificity of 78.14%+/-6.28. Conclusions: Integrating multimodal ultrasound and clinical information enabled promising preoperative MVI prediction in HCC. DCE-US was the main source of predictive information, while BUS, CDFI, and clinical information provided complementary value. The proposed framework may support preoperative risk stratification and individualized clinical decision-making.
Hepatocellular carcinoma (HCC) is biologically heterogeneous, shaped by the interplay between hepatic functional reserve and tumor-related oncologic factors; thus, similar survival outcomes may reflect fundamentally different underlying biological processes. Prognostic modeling in HCC is informed by rich multimodal information from multiparametric MRI and radiology reports from routine clinical practice. Existing prognostic vision-language models (VLMs) learn a single entangled latent representation that blends hepatic and tumor-related factors, limiting both accuracy and biological interpretability. We present BioFact-MoE, a biologically factorized Mixture of Experts (MoE) framework that explicitly decomposes liver and tumor factors via biologically supervised experts within a residual MoE survival architecture. On a HCC cohort of N=588 patients (pretrained on 4,582 3D MRI image-report pairs), BioFact-MoE consistently improves survival prediction over all baselines across time horizons, achieving 12-, 18-, and 24-month AUCs of 75.33%, 75.85%, and 73.96%. Beyond scalar risk prediction, gated expert weights enable phenotype-aware risk stratification. Pathway-informed gating uncovers clinically meaningful treatment-associated survival heterogeneity. In held-out validation, hepatic and tumor embeddings show selective associations with liver function and tumor burden markers, respectively (p<0.05), without supervision. The code is available at https://github.com/jy-639/BioFact-MoE.
Perineural invasion (PNI) is an adverse histopathologic marker in intrahepatic cholangiocarcinoma (ICC), but it is usually confirmed only after resection. Preoperative T2-weighted MRI may provide noninvasive imaging cues predictive of PNI, although labels are available only at the patient level without slice- or voxel-level annotations. We propose Order-Aware Slab Multiple Instance Learning (OAS-MIL), a weakly supervised framework for patient-level PNI prediction. Each tumor-centered MRI crop is represented as an ordered sequence of overlapping 2.5D slabs formed from contiguous axial slices. A shared encoder extracts slab-level features, which are aggregated by a permutation-invariant set-attention branch and a bidirectional sequence-attention branch. Using five-fold label-stratified cross-validation at the patient level, OAS-MIL achieved a mean AUROC of 0.770, outperforming the evaluated volumetric and MIL baselines. These results suggest that axial order provides a useful inductive bias for weakly supervised PNI prediction from MRI.
Hepatocellular carcinoma (HCC) is a common malignancy and a leading cause of cancer-related mortality. Current guidelines and staging systems provide coarse categories, but often miss within-stage heterogeneity and the clinical context in electronic medical records (EMRs). We present HCC-STAR (Hepatocellular Carcinoma Staging, Treatment And pRognosis), a clinically aligned large language model that reads routine EMR narratives and jointly outputs risk score-based staging, ranked guideline-consistent treatments with evidence-based rationales, and individualized survival estimates. We curated about 30,000 HCC cases from SEER and expanded them into EMR-style narrative training data using a clinician-validated, prompt-based augmentation workflow. On this corpus, we developed a knowledge-aligned reasoning framework optimized with a step-verifiable composite reward, moving beyond text-level memorization of clinical guidelines. In a multi-center cohort of 6,668 patients from 12 hospitals in China, HCC-STAR achieved state-of-the-art performance in treatment recommendation and risk stratification compared with clinical guidelines and competitive models, including GPT-5 and Gemini-2.5 Pro. Hypothetical overall-survival analysis showed a median survival of 51 months under adherence to HCC-STAR recommendations, compared with 29 and 32 months under BCLC and CNLC. In clinician-centric evaluations, blinded hepatobiliary specialists rated HCC-STAR's reasoning and evidence-based justifications as trustworthy. The model surpassed resident and attending physicians in treatment accuracy and helped physicians make more accurate decisions faster when used as an assistant. These findings support HCC-STAR as a reliable and verifiable decision-support system for risk stratification and precision therapy in HCC.