Objective: To differentiate combined hepatocellular cholangiocarcinoma (cHCC-CC) from cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) using machine learning on MRI and CT radiomics features.

Methods: This retrospective study included 85 patients aged 32 to 86 years with 86 histopathology-proven liver cancers: 24 cHCC-CC, 24 CC, and 38 HCC who had MRI and CT between 2004 and 2018. Initial CT reports and morphological evaluation of MRI features were used to assess the performance of radiologists read. Following tumor segmentation, 1419 radiomics features were extracted using PyRadiomics library and reduced to 20 principle components by principal component analysis. Support vector machine classifier was utilized to evaluate MRI and CT radiomics features for the prediction of cHCC-CC vs. non-cHCC-CC and HCC vs. non-HCC. Histopathology was the reference standard for all tumors.

Results: Radiomics MRI features demonstrated the best performance for differentiation of cHCC-CC from non-cHCC-CC with the highest AUC of 0.77 (SD 0.19) while CT was of limited value. Contrast-enhanced MRI phases and pre-contrast and portal-phase CT showed excellent performance for the differentiation of HCC from non-HCC (AUC of 0.79 (SD 0.07) to 0.81 (SD 0.13) for MRI and AUC of 0.81 (SD 0.06) and 0.71 (SD 0.15) for CT phases, respectively). The misdiagnosis of cHCC-CC as HCC or CC using radiologists read was 69% for CT and 58% for MRI.

Conclusions: Our results demonstrate promising predictive performance of MRI and CT radiomics features using machine learning analysis for differentiation of cHCC-CC from HCC and CC with potential implications for treatment decisions.

Key points: • Retrospective study demonstrated promising predictive performance of MRI radiomics features in the differentiation of cHCC-CC from HCC and CC and of CT radiomics features in the differentiation of HCC from cHCC-CC and CC. • With future validation, radiomics analysis has the potential to inform current clinical practice for the pre-operative diagnosis of cHCC-CC and to enable optimal treatment decisions regards liver resection and transplantation.