Radiomics for Detection and Differentiation of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis
Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Inclusion and Exclusion Criteria
2.2. Information Sources and Search Strategy
2.3. Study Selection
2.4. Data Extraction
2.5. Quality Assessment
2.6. Meta-Analysis
3. Results
3.1. Study Selection and Characteristics
3.2. Study Participants and Algorithm Characteristics
3.3. Quality Analysis
3.4. Meta-Analysis
3.5. Subgroup Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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| Study | Year | Country | Study Design | Time Period | Comparator | Data Sets | No. of Images per Training Set | No. of Images per Validation Set | No. of Images per Local Test Set | Radiomics/Contrast | Reference Standard |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Xiong et al. [15] | 2025 | China | Retrospective Case–Control | 2015–2020 | HCC patients | Single Center | 396 patients (318 HCC, 78 ICC) | 49 patients (40 HCC, 9 ICC) | 49 | Contrast CT/portal venous | Pathology diagnosis after surgery |
| Liu et al. [16] | 2023 | China | Retrospective Cohort | April 2016–December 2021. | HCC patients | Single Center | 124 | 53 | 53 | MRI/arterial and portal venous phase | Histopathology proven |
| Zhang et al. [17] | 2023 | China | Retrospective Case–Control | - | HCC patients | Single Center | 222 | - | 95 | Contrast CT/arterial and portal venous phase | Manual label for venous phase images |
| Midya et al. [31] | 2018 | USA | Retrospective Cohort | 2000–2015 | HCC patients | Single Center | 156 | 27 | 156 | Contrast CT/portal venous | Histopathology proven |
| Xie et al. [7] | 2025 | China | Retrospective Cohort | May 2008 to January 2024 | Ternary classification of hepatocellular carcinoma (HCC) and Hepatic Inflammatory Pseudotumor (HIPT) | Multicenter | 196 | - | 84 | DCE-MRI/(arterial, portal venous, delayed phases) | Histopathology proven |
| Wang et al. [18] | 2025 | China | Retrospective | - | Hepatic Inflammatory and Pseudotumors (IPT) | Multicenter | 112 | - | 146 | CT contrast scan/multiphase (SOFT, AP, PVP, DP) | Histopathological examination from surgical resection |
| Cheng et al. [19] | 2025 | China | Retrospective | January 2016–October 2023 | Oher primary liver cancers (non-iCCA: HCC and cHCC-iCCA) within PLC. | Single Center | 124 | 178 | CT (non-contrast) and MRI scan/ MRI: T1, T2, DWI, CE-MRI (arterial, venous, 3-min delayed) | Histopathological examination (from surgical resection or biopsy) | |
| Wei et al. [20] | 2024 | China | Retrospective cohort | June 2012–December 2012 | Multiclass liver pathologies (6 types) | Multicenter | 1580 | - | 130M8 | CT contrast scan/arterial and portal venous phase | Histopathology/radiologist consensus |
| Wang et al. [21] | 2024 | China | Retrospective Cohort | - | HCC patients | Single Center | 113 | 49 | 162 | MRI/delayed phase | Histopathology |
| Chen et al. [22] | 2024 | China | Retrospective Cohort | January 2017–September 2020 | HCC and cHCC-ICC patients | Single Center | 332 | 83 | 50 | Single B-mode Ultrasound (BMUS) image | Histopathology (post-resection) |
| Midya et al. [30] | 2023 | USA | Retrospective Cohort | 2003–2015 | HCC, CRLM, and benign liver tumor patients | Multicenter | 488 scans | 162 scans | 814 scans | CT contrast scan/portal venous phase | Histopathology (resection) |
| Mahmoudi et al. [32] | 2023 | Germany | Retrospective Cohort | 2014–2021 | HCC patients | Single Center | 65 | - | 94 | CT contrast scan/arterial phase | Histopathology |
| Hu et al. [23] | 2022 | China | Retrospective Cohort | 2008- 2018 | HCC patients | Multicenter | 344 | 97 | - | MRI scan T1C and T2W/arterial and portal venous phase | Histopathology |
| Huang et al. [24] | 2022 | China | Retrospective Case Control | October 2019–December 2021 | HCC patients | Single Center | 123 | 51 | - | MRI scan T2 WI | Histopathology (surgery/biopsy) |
| Xu et al. [25] | 2022 | China | Retrospective Cohort | August 2018–November 2019 | HCC patients | Single Center | 122 | 89 | 211 | Non-contrast CT | Histopathology |
| Ren et al. [26] | 2021 | China | Retrospective Cohort | January 2019–March 2021 | HCC patients | Multicenter | 149 | 77 | 187 | Ultrasound (grayscale) | Histopathology |
| Xue et al. [27] | 2021 | China | Retrospective Cohort | Jan uary 2005–June 2020 | Inflammatory mass with hepatolithiasis patients | Single Center | 110 | 35 | - | CT contrast scan/arterial and portal venous phase | Histopathology |
| Nakai et al. [33] | 2021 | Japan | Retrospective Cohort | January 2004–September 2019 | HCC patients | Single Center | 493 | 62 | 617 | Non contrast CT scan/late-arterial (23 s post-trigger) and delayed (80 s post-trigger) phase | Histopathology (surgical specimen) |
| Xue et al. [28] | 2021 | China | Retrospective Cohort | January 2005–July 2019 | Inflammatory mass with hepatolithiasis patients | Single Center | 96 | 35 | - | CT contrast scan/arterial phase | |
| Xu et al. [29] | 2021 | China | Retrospective Cohort | 2005–2019 | Inflammatory mass with hepatolithiasis patients | Multicenter | 96 | 35 | 96 | CT contrast scan/arterial phase |
| First Author | ROI | Preprocessing | Model Structure | AI Classifier | Validation | Comparison Algorithms |
|---|---|---|---|---|---|---|
| Xiong et al. [15] (2025) | Manual delineation of tumor boundary by an experienced radiologist, followed by cropping of the minimum rectangular region containing the tumor | ROI images resized to 224 × 224 pixels; data augmentation (rotation, flip) applied to the minority class (ICC) to address imbalance | ConvNeXt-ECSAM (ConvNeXt-T backbone with proposed ECSAM attention modules, fully connected layer for classification) | 2D CNN | Internal hold-out validation (8:1:1 split on patient level) | Compared with ResNet152, DenseNet121, Vision Transformer, Swin Transformer |
| Liu et al. [16] (2023) | Manual segmentation of the entire tumor volume on axial FS-T2WI, AP, and PVP images by a radiologist | Image segmentation, feature extraction using IBEX software (β1.0), Z-score normalization of features | Logistic regression model combining selected radiomics features and clinical risk factors | Radiomics (machine learning–logistic regression) | Internal hold-out validation (7:3 split on patient level) | Compared with individual sequence radiomics models (FS-T2WI, AP, PVP), joint radiomics model (JR), and clinical model (C) |
| Zhang et al. [17] (2023) | Automated segmentation of liver lesion using a modified 2D U-Net, followed by cropping a fixed-size 3D volume (256 × 256 × 36 voxels) around the centroid | Windowing transformation (arterial: [−50, 130] HU; venous: [−45, 205] HU), intensity normalization | 3D dense convolutional network with dual-branch architecture (arterial and venous), followed by a feature fusion network | 3D CNN | Internal hold-out validation (7:3 split on patient level) | Compared with arterial sub-network and venous sub-network alone |
| Midya et al. [31] (2018) | Semi-automated segmentation (Scout Liver) supervised by expert radiologist | Normalization [0, 1], intensity threshold −100 HU to 300 HU, cropped to largest tumor, resized to 299 × 299 pixels | Modified Inception-v3; last 4 layers removed; added 3 fully connected layers with 7000, 1024, 1 nodes; ReLU activations; final SoftMax output | Deep convolutional neural network (modified Inception-v3) | Random split: 70% training, 30% test | No |
| Xie et al. [7] (2025) | Sequences: T2WI, DCE-MRI (arterial, portal venous, delayed phases), DWI | Manual 3D lesion segmentation on ITK-SNAP | Resampling, min–max normalization (0–1), Z-score feature standardization | Logistic regression | Machine learning (radiomics) | Compared with radiomics-only, clinical-only, fusion model |
| Wang et al. [18] (2025) | Manual segmentation of the entire lesion slice-by-slice by two radiologists (>5 yrs experience) using ITK-SNAP, fine-tuned by senior radiologist (>15 yrs) | Spatial matching of ROI to original image, window width/level normalization. | 14 ML models tested (CatBoost, LightGBM, LR, NB, LDA, QDA, KNN, GBC, XGBoost, RF, AdaBoost, ET, DT). Optimal fused model: Linear Discriminant Analysis (LDA) | Machine learning (PyRadiomics feature extraction), LASSO for feature selection, 5-fold CV with grid search for hyperparameter tuning | Internal: 5-fold cross-validation on training set; hold-out test: 70/30 split (training n = 102/test n = 44) | Performance compared among clinical features alone, radiomic features alone, and fused radiomic + clinical features |
| Cheng et al. [19] (2025) | Manual segmentation on largest tumor slice | Resampling to 1 × 1 × 1 mm3, bicubic spline interpolation | ResNet-50 (transfer learning) | Deep learning (ResNet-50), PCA, LASSO, logistic regression | 10-fold cross-validation (training); hold-out test (70/30 split) | Intra-modality: DLRS vs. DLRR vs. radiological model; inter-modality: CT vs. MRI; fused CT-MRI model |
| Wei et al. [20] (2024) | Automatic (YOLOv8 + 3D liver segmentation) | Cropping, normalization, augmentation | ResNet50 + self-supervised pretext + SKD | Deep CNN (ResNet50-based) | Internal test, external validations | Yes (vs. radiologists) |
| Wang et al. [21] (2024) | Original tumor ROI ± expanded regions (−2 to +8 mm) | Resampling to 224 × 224, adaptive histogram equalization, normalization | ResNet50 (pre-trained) for feature extraction + SVM classifier | Deep learning (ResNet50) + machine learning (SVM) | Internal 70:30 split | No |
| Chen et al. [22] (2024) | Single optimal slice showing maximum tumor diameter and details | Data augmentation (rotation, cropping, translation) | ResNet18 (17 convolutional layers, 1 fully connected layer, 4 residual blocks); end-to-end classification | Deep learning (ResNet18) | 5-fold cross-validation on training set, final evaluation on independent test cohort | Vs. MobileNet, DenseNet121, Inception V3 |
| Midya et al. [30] (2023) | Semi-automated tumor segmentation (Scout Liver software (Analogic Corporation, Peabody, MA, USA)) | Thresholding (−100 to 300 HU), normalization (0–1), resizing to 299 × 299 px | Modified Inception v3 (final layers replaced with FC layers: 7000, 1024, 4 nodes) | Deep learning (CNN–transfer learning) | Hold-out (60/20/20 split) | Yes (vs. radiologists, VGG, ResNet, DenseNet, Inception v3) |
| Mahmoudi et al. [32] (2023) | Three spherical VOIs (1 cm diameter) in hypervascular tumor region | StandardScaler normalization, LASSO feature selection | Logistic regression classifier | Machine learning (radiomics) | Hold-out (70% train, 30% test) | Yes (vs. AdaBoost, Stochastic GB, random forest) |
| Hu et al. [23] (2022) | Manual segmentation (3D Slicer) | Feature extraction (IBSI), min–max scaling | TPOT AutoML pipeline | Genetic programming (AutoML) | Hold-out test set | Radiologist performance |
| Huang et al. [24] (2022) | Manual segmentation on largest lesion slice (ITK-SNAP) | ICC > 0.8 for feature stability, mRMR + LASSO for selection | Radiomics nomogram (LASSO + logistic regression) | Radiomics signature | Internal hold-out (7:3 split) | - |
| Xu et al. [25] (2022) | Manual segmentation (3D Slicer) by radiologists | Voxel spacing standardized to 1 × 1 × 1 mm, intensity discretization (bin width = 25 HU) | Feature extraction (Pyradiomics) → feature selection (LASSO) → SVM classification | Support vector machine (SVM) | Internal validation (split-sample) | Radiomics model vs. radiologist evaluation |
| Ren et al. [26] (2021) | Manual segmentation (ITK-SNAP) by experienced radiologists | Normalization, resampling to 1 × 1 mm, gray-level discretization (bin width = 25) | Feature extraction (Pyradiomics) → feature selection (variance filter + LASSO) → SVM classification | Support vector machine (SVM) | Internal test (n = 38) + external validation (n = 39) | Combined vs. clinical vs. ultrasonics-only models |
| Xue et al. [27] (2021) | Manual segmentation of tumor (2 radiologists) | Windowing (W:200, L:45 HU), resampling to 512 × 512, uniform slice thickness 5 mm | Radiomic signature via LASSO logistic regression combining rad score from portal venous and arterial phase | Radiomics (LIFEx) | External validation (second affiliated hospital, n = 35) | No |
| Nakai et al. [33] (2021) | Manual cropping (RectLabel) on representative axial slice ± neighboring slices (9 images/case) | Intensity truncation (–125 to 225 HU), resizing to 70 × 70, normalization (mean = 0, SD = 1) | Custom 3D CNN: 4 convolutional blocks (Conv + ReLU + MaxPool) → fully connected layers (100, 100, 30, 3 nodes) | Convolutional neural network (CNN)–PyTorch (version 1.5.0) | Hold-out test set (n = 62) | One-input model (CT only) vs. two-input model (CT + markers) vs. radiologists |
| Xue et al. [28] (2021) | Manual segmentation of tumor (2 radiologists) | Windowing (W:200, L:45 HU), resampling to 512 × 512, uniform slice thickness 5 mm | Radiomic signature via LASSO logistic regression | Radiomics (LIFEx) | External validation (second affiliated hospital, n = 35) | Yes (vs. clinical model) |
| Xu et al. [29] (2021) | Manual segmentation of tumor mass | Window: 200 HU width, 45 HU level; pixel: 512 × 512 | 1. Radiomic feature extraction (52 features); 2. feature selection (LASSO); 3. model building (logistic regression) | Logistic regression (for Rad-score and comprehensive model) | External validation cohort from another hospital | Yes (radiomic vs. clinical vs. comprehensive model) |
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Alidina, Z.; Banani, I.; Abiha, U.E.; Sultan, U.; Pawlik, T.M. Radiomics for Detection and Differentiation of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis. Cancers 2026, 18, 937. https://doi.org/10.3390/cancers18060937
Alidina Z, Banani I, Abiha UE, Sultan U, Pawlik TM. Radiomics for Detection and Differentiation of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis. Cancers. 2026; 18(6):937. https://doi.org/10.3390/cancers18060937
Chicago/Turabian StyleAlidina, Zayan, Illiyun Banani, Umm E. Abiha, Ujala Sultan, and Timothy M. Pawlik. 2026. "Radiomics for Detection and Differentiation of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis" Cancers 18, no. 6: 937. https://doi.org/10.3390/cancers18060937
APA StyleAlidina, Z., Banani, I., Abiha, U. E., Sultan, U., & Pawlik, T. M. (2026). Radiomics for Detection and Differentiation of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis. Cancers, 18(6), 937. https://doi.org/10.3390/cancers18060937

