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28-09-2024 | Hepatocellular Carcinoma | Hepatobiliary

Advancing microvascular invasion diagnosis: a multi-center investigation of novel MRI-based models for precise detection and classification in early-stage small hepatocellular carcinoma (≤ 3 cm)

Authors: Mengting Gu, Sisi Zhang, Wenjie Zou, Xingyu Zhao, Huilin Chen, RuiLin He, Ningyang Jia, Kairong Song, Wanmin Liu, Peijun Wang

Published in: Abdominal Radiology

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Abstract

Purpose

This study aimed to develop two preoperative magnetic resonance imaging (MRI) based models for detecting and classifying microvascular invasion (MVI) in early-stage small hepatocellular carcinoma (sHCC) patients.

Methods

MVI is graded as M0 (no invasion), M1 (invasion of five or fewer vessels located within 1 cm of the tumor’s peritumoral region), and M2 (invasion of more than five vessels or those located more than 1 cm from the tumor’s surface). This study enrolled 395 early-stage sHCC (≤ 3 cm) patients from three centers who underwent preoperative gadopentetate-enhanced MRI. From the first two centers, 310 patients were randomly divided into training (n = 217) and validation (n = 93) cohorts in a 7:3 ratio to develop the first model for predicting MVI presence. Among these, 153 patients with identified MVI were further divided into training (n = 112) and validation (n = 41) cohorts, using the same ratio, to construct the second model for MVI classification. An independent test cohort of 85 patients from the third center to validate both models. Univariate and multivariate logistic regression analyses identified independent predictors of MVI and its classification in the training cohorts. Based on these predictors, two nomograms were developed and assessed for their discriminative ability, calibration, and clinical usefulness. Besides, considering the two models are supposed applied in a serial fashion in the real clinical setting, we evaluate the performance of the two models together on the test cohorts by applying them simultaneously. Kaplan–Meier survival curve analysis was employed to assess the correlation between predicted MVI status and early recurrence, similar to the association observed with actual MVI status and early recurrence.

Results

The MVI detection nomogram, with platelet count (PLT), activated partial thromboplastin time (APTT), rim arterial phase hyperenhancement (Rim APHE) and arterial peritumoral enhancement, achieved area under the curve (AUC) of 0.827, 0.761 and 0.798 in the training, validation, and test cohorts, respectively. The MVI classification nomogram, integrating Total protein (TP), Shape, Arterial peritumoral enhancement and enhancement pattern, achieved AUC of 0.824, 0.772, and 0.807 across the three cohorts. When the two models were applied on the test cohorts in a serial fashion, they both demonstrated good performance, which means the two models had good clinical applicability. Calibration and decision curve analysis (DCA) results affirmed the model’s reliability and clinical utility. Notably, early recurrence was more prevalent in the MVI grade 2 (M2) group compared to the MVI-absent and M1 groups, regardless of the actual or predicted MVI status.

Conclusions

The nomograms exhibited excellent predictive performance for detecting and classifying MVI in patients with early-stage sHCC, particularly identifying high-risk M2 patients preoperatively.
Appendix
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Literature
1.
go back to reference Calderaro, J., et al., Artificial intelligence for the prevention and clinical management of hepatocellular carcinoma. J Hepatol, 2022. 76(6): p. 1348-1361.PubMedPubMedCentralCrossRef Calderaro, J., et al., Artificial intelligence for the prevention and clinical management of hepatocellular carcinoma. J Hepatol, 2022. 76(6): p. 1348-1361.PubMedPubMedCentralCrossRef
2.
go back to reference Lei, Z., et al., Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria. JAMA Surg, 2016. 151(4): p. 356-63.PubMedCrossRef Lei, Z., et al., Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria. JAMA Surg, 2016. 151(4): p. 356-63.PubMedCrossRef
3.
go back to reference Devan, A.R., et al., Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence. Cancers (Basel), 2023. 15(10).CrossRefPubMed Devan, A.R., et al., Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence. Cancers (Basel), 2023. 15(10).CrossRefPubMed
5.
go back to reference Gilles, H., T. Garbutt, and J. Landrum, Hepatocellular Carcinoma. Crit Care Nurs Clin North Am, 2022. 34(3): p. 289-301.PubMedCrossRef Gilles, H., T. Garbutt, and J. Landrum, Hepatocellular Carcinoma. Crit Care Nurs Clin North Am, 2022. 34(3): p. 289-301.PubMedCrossRef
6.
go back to reference Kim, B., J. Kahn, and N.A. Terrault, Liver transplantation as therapy for hepatocellular carcinoma. Liver Int, 2020. 40 Suppl 1: p. 116-121.PubMedCrossRef Kim, B., J. Kahn, and N.A. Terrault, Liver transplantation as therapy for hepatocellular carcinoma. Liver Int, 2020. 40 Suppl 1: p. 116-121.PubMedCrossRef
7.
go back to reference Tampaki, M., G.V. Papatheodoridis, and E. Cholongitas, Intrahepatic recurrence of hepatocellular carcinoma after resection: an update. Clin J Gastroenterol, 2021. 14(3): p. 699-713.PubMedCrossRef Tampaki, M., G.V. Papatheodoridis, and E. Cholongitas, Intrahepatic recurrence of hepatocellular carcinoma after resection: an update. Clin J Gastroenterol, 2021. 14(3): p. 699-713.PubMedCrossRef
8.
go back to reference Chan, A.W.H., et al., Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol, 2018. 69(6): p. 1284-1293.PubMedCrossRef Chan, A.W.H., et al., Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol, 2018. 69(6): p. 1284-1293.PubMedCrossRef
9.
go back to reference Ji, M., et al., Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy. Front Surg, 2022. 9: p. 1042431.PubMedPubMedCentralCrossRef Ji, M., et al., Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy. Front Surg, 2022. 9: p. 1042431.PubMedPubMedCentralCrossRef
10.
11.
go back to reference Zhang, X., et al., Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma. J Gastroenterol Hepatol, 2018. 33(2): p. 347-354.PubMedCrossRef Zhang, X., et al., Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma. J Gastroenterol Hepatol, 2018. 33(2): p. 347-354.PubMedCrossRef
12.
go back to reference Cai, Y., et al., Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma. Cell Death Dis, 2022. 13(2): p. 176.PubMedPubMedCentralCrossRef Cai, Y., et al., Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma. Cell Death Dis, 2022. 13(2): p. 176.PubMedPubMedCentralCrossRef
13.
go back to reference Sheng, X., et al., A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC. Hepatol Int, 2020. 14(6): p. 1034-1047.PubMedCrossRef Sheng, X., et al., A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC. Hepatol Int, 2020. 14(6): p. 1034-1047.PubMedCrossRef
14.
go back to reference Wei, M.C., et al., Adjuvant Sorafenib Following Radiofrequency Ablation for Early-Stage Recurrent Hepatocellular Carcinoma With Microvascular Invasion at the Initial Hepatectomy. Front Oncol, 2022. 12: p. 868429.PubMedPubMedCentralCrossRef Wei, M.C., et al., Adjuvant Sorafenib Following Radiofrequency Ablation for Early-Stage Recurrent Hepatocellular Carcinoma With Microvascular Invasion at the Initial Hepatectomy. Front Oncol, 2022. 12: p. 868429.PubMedPubMedCentralCrossRef
15.
go back to reference Wang, L., et al., Postoperative adjuvant treatment strategy for hepatocellular carcinoma with microvascular invasion: a non-randomized interventional clinical study. BMC Cancer, 2020. 20(1): p. 614.PubMedPubMedCentralCrossRef Wang, L., et al., Postoperative adjuvant treatment strategy for hepatocellular carcinoma with microvascular invasion: a non-randomized interventional clinical study. BMC Cancer, 2020. 20(1): p. 614.PubMedPubMedCentralCrossRef
16.
go back to reference Erstad, D.J. and K.K. Tanabe, Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma. Ann Surg Oncol, 2019. 26(5): p. 1474-1493.PubMedCrossRef Erstad, D.J. and K.K. Tanabe, Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma. Ann Surg Oncol, 2019. 26(5): p. 1474-1493.PubMedCrossRef
17.
go back to reference Li, L., et al., Radiomics for the Preoperative Evaluation of Microvascular Invasion in Hepatocellular Carcinoma: A Meta-Analysis. Front Oncol, 2022. 12: p. 831996.PubMedPubMedCentralCrossRef Li, L., et al., Radiomics for the Preoperative Evaluation of Microvascular Invasion in Hepatocellular Carcinoma: A Meta-Analysis. Front Oncol, 2022. 12: p. 831996.PubMedPubMedCentralCrossRef
18.
go back to reference Lee, S., et al., Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol, 2017. 67(3): p. 526-534.PubMedCrossRef Lee, S., et al., Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol, 2017. 67(3): p. 526-534.PubMedCrossRef
19.
go back to reference Zhang, L., et al., Prediction of HCC microvascular invasion with gadobenate-enhanced MRI: correlation with pathology. Eur Radiol, 2020. 30(10): p. 5327-5336.PubMedCrossRef Zhang, L., et al., Prediction of HCC microvascular invasion with gadobenate-enhanced MRI: correlation with pathology. Eur Radiol, 2020. 30(10): p. 5327-5336.PubMedCrossRef
20.
go back to reference Feng, S.T., et al., Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI. Eur Radiol, 2019. 29(9): p. 4648-4659.PubMedCrossRef Feng, S.T., et al., Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI. Eur Radiol, 2019. 29(9): p. 4648-4659.PubMedCrossRef
21.
go back to reference Chernyak, V., et al., Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology, 2018. 289(3): p. 816-830.PubMedCrossRef Chernyak, V., et al., Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology, 2018. 289(3): p. 816-830.PubMedCrossRef
22.
go back to reference Tang, M., et al., Nomogram development and validation to predict hepatocellular carcinoma tumor behavior by preoperative gadoxetic acid-enhanced MRI. Eur Radiol, 2021. 31(11): p. 8615-8627.PubMedCrossRef Tang, M., et al., Nomogram development and validation to predict hepatocellular carcinoma tumor behavior by preoperative gadoxetic acid-enhanced MRI. Eur Radiol, 2021. 31(11): p. 8615-8627.PubMedCrossRef
23.
go back to reference Huang, M., et al., Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation. Contrast Media Mol Imaging, 2018. 2018: p. 9674565.PubMedPubMedCentralCrossRef Huang, M., et al., Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation. Contrast Media Mol Imaging, 2018. 2018: p. 9674565.PubMedPubMedCentralCrossRef
24.
go back to reference Zhou, C., et al., Histopathological components correlated with MRI features and prognosis in combined hepatocellular carcinoma-cholangiocarcinoma. Eur Radiol, 2022. 32(10): p. 6702-6711.PubMedCrossRef Zhou, C., et al., Histopathological components correlated with MRI features and prognosis in combined hepatocellular carcinoma-cholangiocarcinoma. Eur Radiol, 2022. 32(10): p. 6702-6711.PubMedCrossRef
25.
go back to reference Kawamura, Y., et al., New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma. Hepatol Res, 2010. 40(10): p. 1006-14.PubMedCrossRef Kawamura, Y., et al., New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma. Hepatol Res, 2010. 40(10): p. 1006-14.PubMedCrossRef
26.
go back to reference Rimola, J., et al., Reliability of extracellular contrast versus gadoxetic acid in assessing small liver lesions using liver imaging reporting and data system v.2018 and European association for the study of the liver criteria. Hepatology, 2022. 76(5): p. 1318-1328.PubMedCrossRef Rimola, J., et al., Reliability of extracellular contrast versus gadoxetic acid in assessing small liver lesions using liver imaging reporting and data system v.2018 and European association for the study of the liver criteria. Hepatology, 2022. 76(5): p. 1318-1328.PubMedCrossRef
27.
go back to reference Choi, Y.S., et al., Histological characteristics of small hepatocellular carcinomas showing atypical enhancement patterns on gadoxetic acid-enhanced MR imaging. J Magn Reson Imaging, 2013. 37(6): p. 1384-91.PubMedCrossRef Choi, Y.S., et al., Histological characteristics of small hepatocellular carcinomas showing atypical enhancement patterns on gadoxetic acid-enhanced MR imaging. J Magn Reson Imaging, 2013. 37(6): p. 1384-91.PubMedCrossRef
28.
go back to reference Takayasu, K., et al., Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. Liver Int, 2013. 33(5): p. 762-70.PubMedCrossRef Takayasu, K., et al., Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. Liver Int, 2013. 33(5): p. 762-70.PubMedCrossRef
29.
go back to reference Kim, M.J., et al., Imaging features of small hepatocellular carcinomas with microvascular invasion on gadoxetic acid-enhanced MR imaging. Eur J Radiol, 2012. 81(10): p. 2507-12.PubMedCrossRef Kim, M.J., et al., Imaging features of small hepatocellular carcinomas with microvascular invasion on gadoxetic acid-enhanced MR imaging. Eur J Radiol, 2012. 81(10): p. 2507-12.PubMedCrossRef
30.
go back to reference Uno, H., et al., On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med, 2011. 30(10): p. 1105-17.PubMedPubMedCentralCrossRef Uno, H., et al., On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med, 2011. 30(10): p. 1105-17.PubMedPubMedCentralCrossRef
32.
33.
go back to reference Akinci D’Antonoli, T. and N.D. Mercaldo, Obsolescence of nomograms in radiomics research. Eur Radiol, 2023. 33(11): p. 7477–7478. Akinci D’Antonoli, T. and N.D. Mercaldo, Obsolescence of nomograms in radiomics research. Eur Radiol, 2023. 33(11): p. 7477–7478.
34.
go back to reference Xu, W., R. Li, and F. Liu, Novel Prognostic Nomograms for Predicting Early and Late Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy. Cancer Manag Res, 2020. 12: p. 1693-1712.PubMedPubMedCentralCrossRef Xu, W., R. Li, and F. Liu, Novel Prognostic Nomograms for Predicting Early and Late Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy. Cancer Manag Res, 2020. 12: p. 1693-1712.PubMedPubMedCentralCrossRef
35.
go back to reference Zheng, X., et al., Predictive value of radiomics analysis of enhanced CT for three-tiered microvascular invasion grading in hepatocellular carcinoma. Med Phys, 2023. 50(10): p. 6079-6095.PubMedCrossRef Zheng, X., et al., Predictive value of radiomics analysis of enhanced CT for three-tiered microvascular invasion grading in hepatocellular carcinoma. Med Phys, 2023. 50(10): p. 6079-6095.PubMedCrossRef
36.
go back to reference Pinato, D.J., et al., PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma. BMC Cancer, 2021. 21(1): p. 301.PubMedPubMedCentralCrossRef Pinato, D.J., et al., PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma. BMC Cancer, 2021. 21(1): p. 301.PubMedPubMedCentralCrossRef
37.
go back to reference Liou, H., et al., Neoadjuvant Radiation Lobectomy and Immunotherapy for Angioinvasive HCC Resulting in Complete Pathologic Response. Hepatology, 2021. 74(1): p. 525-527.PubMedCrossRef Liou, H., et al., Neoadjuvant Radiation Lobectomy and Immunotherapy for Angioinvasive HCC Resulting in Complete Pathologic Response. Hepatology, 2021. 74(1): p. 525-527.PubMedCrossRef
38.
go back to reference Li, M.G., et al., Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters. Oncol Lett, 2024. 28(1): p. 310.PubMedPubMedCentralCrossRef Li, M.G., et al., Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters. Oncol Lett, 2024. 28(1): p. 310.PubMedPubMedCentralCrossRef
39.
go back to reference Chen, S., et al., Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses. Front Oncol, 2021. 11: p. 774800.PubMedCrossRef Chen, S., et al., Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses. Front Oncol, 2021. 11: p. 774800.PubMedCrossRef
40.
go back to reference An, C., et al., Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. Radiology, 2015. 276(2): p. 433-43.PubMedCrossRef An, C., et al., Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. Radiology, 2015. 276(2): p. 433-43.PubMedCrossRef
41.
go back to reference Miyata, R., et al., Accuracy of preoperative prediction of microinvasion of portal vein in hepatocellular carcinoma using superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography. J Gastroenterol, 2006. 41(10): p. 987-95.PubMedCrossRef Miyata, R., et al., Accuracy of preoperative prediction of microinvasion of portal vein in hepatocellular carcinoma using superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography. J Gastroenterol, 2006. 41(10): p. 987-95.PubMedCrossRef
42.
go back to reference Kim, H., et al., Can microvessel invasion of hepatocellular carcinoma be predicted by pre-operative MRI? Eur Radiol, 2009. 19(7): p. 1744-51.PubMedCrossRef Kim, H., et al., Can microvessel invasion of hepatocellular carcinoma be predicted by pre-operative MRI? Eur Radiol, 2009. 19(7): p. 1744-51.PubMedCrossRef
43.
go back to reference Cannella, R., et al., Association of LI-RADS and Histopathologic Features with Survival in Patients with Solitary Resected Hepatocellular Carcinoma. Radiology, 2024. 310(2): p. e231160.PubMedCrossRef Cannella, R., et al., Association of LI-RADS and Histopathologic Features with Survival in Patients with Solitary Resected Hepatocellular Carcinoma. Radiology, 2024. 310(2): p. e231160.PubMedCrossRef
44.
go back to reference Yang, L., et al., A Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Liver Cancer, 2019. 8(5): p. 373-386.PubMedCrossRef Yang, L., et al., A Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Liver Cancer, 2019. 8(5): p. 373-386.PubMedCrossRef
45.
go back to reference Wang, L.L., et al., The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma. Medicine (Baltimore), 2021. 100(20): p. e25804.PubMedCrossRef Wang, L.L., et al., The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma. Medicine (Baltimore), 2021. 100(20): p. e25804.PubMedCrossRef
46.
go back to reference Witjes, C.D., et al., Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast-enhanced MRI. J Magn Reson Imaging, 2012. 36(3): p. 641-7.PubMedCrossRef Witjes, C.D., et al., Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast-enhanced MRI. J Magn Reson Imaging, 2012. 36(3): p. 641-7.PubMedCrossRef
Metadata
Title
Advancing microvascular invasion diagnosis: a multi-center investigation of novel MRI-based models for precise detection and classification in early-stage small hepatocellular carcinoma (≤ 3 cm)
Authors
Mengting Gu
Sisi Zhang
Wenjie Zou
Xingyu Zhao
Huilin Chen
RuiLin He
Ningyang Jia
Kairong Song
Wanmin Liu
Peijun Wang
Publication date
28-09-2024
Publisher
Springer US
Published in
Abdominal Radiology
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-024-04463-w

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