Skip to main content
Top
Published in: European Radiology 4/2020

01-04-2020 | Ultrasound | Imaging Informatics and Artificial Intelligence

Accurate prediction of responses to transarterial chemoembolization for patients with hepatocellular carcinoma by using artificial intelligence in contrast-enhanced ultrasound

Authors: Dan Liu, Fei Liu, Xiaoyan Xie, Liya Su, Ming Liu, Xiaohua Xie, Ming Kuang, Guangliang Huang, Yuqi Wang, Hui Zhou, Kun Wang, Manxia Lin, Jie Tian

Published in: European Radiology | Issue 4/2020

Login to get access

Abstract

Objectives

We aimed to establish and validate an artificial intelligence–based radiomics strategy for predicting personalized responses of hepatocellular carcinoma (HCC) to first transarterial chemoembolization (TACE) session by quantitatively analyzing contrast-enhanced ultrasound (CEUS) cines.

Methods

One hundred and thirty HCC patients (89 for training, 41 for validation), who received ultrasound examination (CEUS and B-mode) within 1 week before the first TACE session, were retrospectively enrolled. Ultrasonographic data was used for building and validating deep learning radiomics-based CEUS model (R-DLCEUS), machine learning radiomics-based time-intensity curve of CEUS model (R-TIC), and machine learning radiomics-based B-Mode images model (R-BMode), respectively, to predict responses (objective-response and non-response) to TACE with reference to modified response evaluation criteria in solid tumor. The performance of models was compared by areas under the receiver operating characteristic curve (AUC) and the DeLong test was used to compare different AUCs. The prediction robustness was assessed for each model.

Results

AUCs of R-DLCEUS, R-TIC, and R-BMode were 0.93 (95% CI, 0.80–0.98), 0.80 (95% CI, 0.64–0.90), and 0.81 (95% CI, 0.67–0.95) in the validation cohort, respectively. AUC of R-DLCEUS shows significant difference compared with that of R-TIC (p = 0.034) and R-BMode (p = 0.039), whereas R-TIC was not significantly different from R-BMode. The performance was highly reproducible with different training and validation cohorts.

Conclusions

DL-based radiomics method can effectively utilize CEUS cines to achieve accurate and personalized prediction. It is easy to operate and holds good potential for benefiting TACE candidates in clinical practice.

Key Points

• Deep learning (DL) radiomics-based CEUS model can accurately predict responses of HCC patients to their first TACE session by quantitatively analyzing their pre-operative CEUS cines.
• The visualization of the 3D CNN analysis adopted in CEUS model provided direct insight into what computers “see” on CEUS cines, which can help people understand the interpretation of CEUS data.
• The proposed prediction method is easy to operate and labor-saving for clinical practice, facilitating the clinical treatment decision of HCCs with very few time costs.
Appendix
Available only for authorised users
Literature
1.
go back to reference Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358–380CrossRef Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358–380CrossRef
2.
go back to reference Park J, Chen M, Colombo M et al (2015) Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver Int 35:2155–2166CrossRef Park J, Chen M, Colombo M et al (2015) Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver Int 35:2155–2166CrossRef
3.
go back to reference Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF (2016) Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology 64:106–116CrossRef Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF (2016) Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology 64:106–116CrossRef
4.
go back to reference Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation vs. symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739CrossRef Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation vs. symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739CrossRef
5.
go back to reference Peng ZW, Zhang YJ, Chen MS et al (2013) Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol 31:426–432CrossRef Peng ZW, Zhang YJ, Chen MS et al (2013) Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol 31:426–432CrossRef
6.
go back to reference Meyer T, Fox R, Ma YT et al (2017) Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2:565–575CrossRef Meyer T, Fox R, Ma YT et al (2017) Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2:565–575CrossRef
7.
go back to reference Kim BK, Kim SU, Kim KA et al (2015) Complete response at first chemoembolization is still the most robust predictor for favorable outcome in hepatocellular carcinoma. J Hepatol 62:1304–1310CrossRef Kim BK, Kim SU, Kim KA et al (2015) Complete response at first chemoembolization is still the most robust predictor for favorable outcome in hepatocellular carcinoma. J Hepatol 62:1304–1310CrossRef
8.
go back to reference Kim BK, Kim KA, Park JY et al (2013) Prospective comparison of prognostic values of modified response evaluation criteria in solid tumours with European Association for the Study of the liver criteria in hepatocellular carcinoma following chemoembolisation. Eur J Cancer 49:826–834CrossRef Kim BK, Kim KA, Park JY et al (2013) Prospective comparison of prognostic values of modified response evaluation criteria in solid tumours with European Association for the Study of the liver criteria in hepatocellular carcinoma following chemoembolisation. Eur J Cancer 49:826–834CrossRef
9.
go back to reference European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236CrossRef European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236CrossRef
10.
go back to reference Loosen SH, Schulze-Hagen M, Leyh C et al (2018) IL-6 and IL-8 serum levels predict tumor response and overall survival after TACE for primary and secondary hepatic malignancies. Int J Mol Sci 19:E1766CrossRef Loosen SH, Schulze-Hagen M, Leyh C et al (2018) IL-6 and IL-8 serum levels predict tumor response and overall survival after TACE for primary and secondary hepatic malignancies. Int J Mol Sci 19:E1766CrossRef
11.
go back to reference Abajian A, Murali N, Savic LJ et al (2018) Predicting treatment response to intra-arterial therapies for hepatocellular carcinoma with the use of supervised machine learning-an artificial intelligence concept. J Vasc Interv Radiol 29:850–857CrossRef Abajian A, Murali N, Savic LJ et al (2018) Predicting treatment response to intra-arterial therapies for hepatocellular carcinoma with the use of supervised machine learning-an artificial intelligence concept. J Vasc Interv Radiol 29:850–857CrossRef
12.
go back to reference Lahrsow M, Albrecht MH, Bickford MW, Vogl TJ (2017) Predicting treatment response of colorectal cancer liver metastases to conventional lipiodol-based transarterial chemoembolization using diffusion-weighted MR imaging: value of pretreatment apparent diffusion coefficients (ADC) and ADC changes under therapy. Cardiovasc Intervent Radiol 40:852–859CrossRef Lahrsow M, Albrecht MH, Bickford MW, Vogl TJ (2017) Predicting treatment response of colorectal cancer liver metastases to conventional lipiodol-based transarterial chemoembolization using diffusion-weighted MR imaging: value of pretreatment apparent diffusion coefficients (ADC) and ADC changes under therapy. Cardiovasc Intervent Radiol 40:852–859CrossRef
13.
go back to reference Kadalayil L, Benini R, Pallan L et al (2013) A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol 24:2565–2570CrossRef Kadalayil L, Benini R, Pallan L et al (2013) A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol 24:2565–2570CrossRef
14.
go back to reference Hucke F, Pinter M, Graziadei I et al (2014) How to STATE suitability and START transarterial chemoembolization in patients with intermediate stage hepatocellular carcinoma. J Hepatol 61:1287–1296CrossRef Hucke F, Pinter M, Graziadei I et al (2014) How to STATE suitability and START transarterial chemoembolization in patients with intermediate stage hepatocellular carcinoma. J Hepatol 61:1287–1296CrossRef
15.
go back to reference Sieghart W, Hucke F, Pinter M et al (2013) The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 57:2261–2273CrossRef Sieghart W, Hucke F, Pinter M et al (2013) The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 57:2261–2273CrossRef
16.
go back to reference Alzaraa A, Gravante G, Chung WY et al (2013) Contrast-enhanced ultrasound in the preoperative, intraoperative and postoperative assessment of liver lesions. Hepatol Res 43:809–819CrossRef Alzaraa A, Gravante G, Chung WY et al (2013) Contrast-enhanced ultrasound in the preoperative, intraoperative and postoperative assessment of liver lesions. Hepatol Res 43:809–819CrossRef
17.
go back to reference Moschouris H, Malagari K, Marinis A et al (2012) Hepatocellular carcinoma treated with transarterial chemoembolization: evaluation with parametric contrast-enhanced ultrasonography. World J Radiol 4:379–386CrossRef Moschouris H, Malagari K, Marinis A et al (2012) Hepatocellular carcinoma treated with transarterial chemoembolization: evaluation with parametric contrast-enhanced ultrasonography. World J Radiol 4:379–386CrossRef
18.
go back to reference Song J, Shi J, Dong D et al (2018) A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy. Clin Cancer Res 24:3583–3592CrossRef Song J, Shi J, Dong D et al (2018) A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy. Clin Cancer Res 24:3583–3592CrossRef
19.
go back to reference Wang K, Lu X, Zhou H et al (2019) Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study. Gut 68:729–741CrossRef Wang K, Lu X, Zhou H et al (2019) Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study. Gut 68:729–741CrossRef
20.
go back to reference Liu Z, Zhang XY, Shi YJ et al (2017) Radiomics analysis for evaluation of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clin Cancer Res 23:1038–2017 Liu Z, Zhang XY, Shi YJ et al (2017) Radiomics analysis for evaluation of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clin Cancer Res 23:1038–2017
21.
go back to reference Kermany DS, Goldbaum M, Cai W et al (2018) Identifyingmedical diagnoses and treatable diseases by image-based deep learning. Cell 172:1122–1131CrossRef Kermany DS, Goldbaum M, Cai W et al (2018) Identifyingmedical diagnoses and treatable diseases by image-based deep learning. Cell 172:1122–1131CrossRef
22.
go back to reference Huang YQ, Liang CH, He L et al (2016) Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer. J Clin Oncol 34:2157–2164CrossRef Huang YQ, Liang CH, He L et al (2016) Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer. J Clin Oncol 34:2157–2164CrossRef
23.
go back to reference Liu M, Lin M, Lu M et al (2015) Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST. Eur Radiol 25:2502–2511CrossRef Liu M, Lin M, Lu M et al (2015) Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST. Eur Radiol 25:2502–2511CrossRef
24.
go back to reference Georgiades C, Geschwind JF, Harrison N et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265:115–123CrossRef Georgiades C, Geschwind JF, Harrison N et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265:115–123CrossRef
25.
go back to reference Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60CrossRef Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60CrossRef
26.
go back to reference Edeline J, Boucher E, Rolland Y et al (2012) Comparison of tumor response by response evaluation criteria in solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 118:147–156CrossRef Edeline J, Boucher E, Rolland Y et al (2012) Comparison of tumor response by response evaluation criteria in solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 118:147–156CrossRef
27.
go back to reference Yushkevich PA, Piven J, Hazlett HC et al (2006) User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31:1116–1128CrossRef Yushkevich PA, Piven J, Hazlett HC et al (2006) User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31:1116–1128CrossRef
28.
go back to reference Kono Y, Lyshchik A, Cosgrove D et al (2017) Contrast enhanced ultrasound (CEUS) liver imaging reporting and data system (LIRADS®): the official version by the American College of Radiology (ACR). Ultraschall Med 38:85–86CrossRef Kono Y, Lyshchik A, Cosgrove D et al (2017) Contrast enhanced ultrasound (CEUS) liver imaging reporting and data system (LIRADS®): the official version by the American College of Radiology (ACR). Ultraschall Med 38:85–86CrossRef
29.
go back to reference Ta CN, Eghtedari M, Mattrey RF et al (2014) 2-tier in-plane motion correction and out-of-plane motion filtering for contrast-enhanced ultrasound. Investig Radiol 49:707–719CrossRef Ta CN, Eghtedari M, Mattrey RF et al (2014) 2-tier in-plane motion correction and out-of-plane motion filtering for contrast-enhanced ultrasound. Investig Radiol 49:707–719CrossRef
30.
go back to reference Tran D, Bourdev L, Fergus R et al (2015) Learning spatiotemporal features with 3D convolutional networks. arXiv:1412.0767 Tran D, Bourdev L, Fergus R et al (2015) Learning spatiotemporal features with 3D convolutional networks. arXiv:1412.0767
31.
go back to reference Feichtenhofer C, Pinz A, Zisserman A (2016) Convolutional twostream network fusion for video action recognition. arXiv: 1604.06573 Feichtenhofer C, Pinz A, Zisserman A (2016) Convolutional twostream network fusion for video action recognition. arXiv: 1604.06573
32.
go back to reference Wang L, Xiong Y, Wang Z et al (2016) Temporal segment networks: towards good practices for deep action recognition. arXiv: 1608.00859 Wang L, Xiong Y, Wang Z et al (2016) Temporal segment networks: towards good practices for deep action recognition. arXiv: 1608.00859
33.
go back to reference Srivastava N, Mansimov E, Salakhutdinov R (2016) Unsupervised learning of video representations using LSTMs. arXiv:1502.04681 Srivastava N, Mansimov E, Salakhutdinov R (2016) Unsupervised learning of video representations using LSTMs. arXiv:1502.04681
34.
go back to reference Goodfellow I, Bengio Y, Courville A (2016) Deep Learning, MIT Press Goodfellow I, Bengio Y, Courville A (2016) Deep Learning, MIT Press
35.
go back to reference Francois C (2016) Xception: deep learning with depthwise separable convolutions. arXiv:1610.02357 Francois C (2016) Xception: deep learning with depthwise separable convolutions. arXiv:1610.02357
36.
go back to reference Zhang B, Zhao Q, Feng W et al (2018) AlphaMEX: a smarter global pooling method for convolutional neural networks. Neurocomputing:36–48 Zhang B, Zhao Q, Feng W et al (2018) AlphaMEX: a smarter global pooling method for convolutional neural networks. Neurocomputing:36–48
37.
go back to reference Friedman JH (2001) Greedy function approximation: a gradient boosting machine. Ann Stat 29:1189–1232CrossRef Friedman JH (2001) Greedy function approximation: a gradient boosting machine. Ann Stat 29:1189–1232CrossRef
38.
go back to reference Cortes C, Vapnik V (1995) Support-vector networks. Mach Learn 20:273–297 Cortes C, Vapnik V (1995) Support-vector networks. Mach Learn 20:273–297
39.
go back to reference Varma S, Simon R (2006) Bias in error estimation when using cross-validation for model selection. BMC Bioinformatics 7:91CrossRef Varma S, Simon R (2006) Bias in error estimation when using cross-validation for model selection. BMC Bioinformatics 7:91CrossRef
40.
go back to reference Ta CN, Kono Y, Eghtedari M et al (2017) Focal liver lesions: computer-aided diagnosis by using contrast-enhanced US cine recordings. Radiology 286:1062–1071CrossRef Ta CN, Kono Y, Eghtedari M et al (2017) Focal liver lesions: computer-aided diagnosis by using contrast-enhanced US cine recordings. Radiology 286:1062–1071CrossRef
41.
go back to reference Selvaraju RR, Cogswell M, Das A (2017) Grad-CAM: visual explanations from deep networks via gradient-based localization. arXiv:1610.02391 Selvaraju RR, Cogswell M, Das A (2017) Grad-CAM: visual explanations from deep networks via gradient-based localization. arXiv:1610.02391
42.
go back to reference MJG L, Vedder MM, JCM W et al (2014) Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician’s guide. Ann Intern Med 160:122–131 MJG L, Vedder MM, JCM W et al (2014) Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician’s guide. Ann Intern Med 160:122–131
43.
go back to reference van Griethuysen JJM, Fedorov A, Parmar C et al (2017) Computational radiomics system to decode the radiographic phenotype. Cancer Res 77:104–107CrossRef van Griethuysen JJM, Fedorov A, Parmar C et al (2017) Computational radiomics system to decode the radiographic phenotype. Cancer Res 77:104–107CrossRef
44.
go back to reference Bruix J, Sala M, Llovet JM (2004) Chemoembolization for hepatocellular carcinoma. Gastroenterology 127:S179–S188CrossRef Bruix J, Sala M, Llovet JM (2004) Chemoembolization for hepatocellular carcinoma. Gastroenterology 127:S179–S188CrossRef
45.
go back to reference Zhou LQ, Wang JY, Yu SY et al (2019) Artificial intelligence in medical imaging of the liver. World J Gastroenterol 25:672–682CrossRef Zhou LQ, Wang JY, Yu SY et al (2019) Artificial intelligence in medical imaging of the liver. World J Gastroenterol 25:672–682CrossRef
46.
go back to reference Iwamoto S, Sanefuji H, Okuda K (2003) Angiographic subsegmentectomy for the treatment of patients with small hepatocellular carcinoma. Cancer 97:1051–1056CrossRef Iwamoto S, Sanefuji H, Okuda K (2003) Angiographic subsegmentectomy for the treatment of patients with small hepatocellular carcinoma. Cancer 97:1051–1056CrossRef
47.
go back to reference Matsui O, Kadoya M, Yoshikawa J et al (1993) Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization. Radiology 188:79–83CrossRef Matsui O, Kadoya M, Yoshikawa J et al (1993) Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization. Radiology 188:79–83CrossRef
Metadata
Title
Accurate prediction of responses to transarterial chemoembolization for patients with hepatocellular carcinoma by using artificial intelligence in contrast-enhanced ultrasound
Authors
Dan Liu
Fei Liu
Xiaoyan Xie
Liya Su
Ming Liu
Xiaohua Xie
Ming Kuang
Guangliang Huang
Yuqi Wang
Hui Zhou
Kun Wang
Manxia Lin
Jie Tian
Publication date
01-04-2020
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 4/2020
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-019-06553-6

Other articles of this Issue 4/2020

European Radiology 4/2020 Go to the issue