The course and prognostic value of tumor stiffness detected by ultrasound elastography for transarterial chemoembolization of hepatocellular carcinoma

Suyun Hou, Shaohua Hua, Kefei Cui, Feng Liu, Ke Ding, Jiaxiang Yuan, Suyun Hou, Shaohua Hua, Kefei Cui, Feng Liu, Ke Ding, Jiaxiang Yuan

Abstract

Background: Transarterial chemoembolization (TACE) is recommended as the first-line treatment in intermediate-stage patients with hepatocellular carcinoma (HCC) or as a palliative treatment modality in advanced patients. However, tumor control usually requires multiple TACE interventions due to the presence of residual and recurrent lesions. Elastography can provide information about tumor stiffness (TS) to predict tumor residual or recurrence. In this study, we aimed to analyze the effects of TACE on HCC stiffness using ultrasound elastography (US-E). We investigated whether quantifying TS using US-E could predict the recurrence of HCC.

Methods: This retrospective cohort study included 116 patients undergoing TACE to treat HCC. US-E was performed to measure the tumor's elastic modulus within 3 days before TACE, in the 2 days after the intervention, and at the 1-month follow-up. The known prognostic factors of HCC were also analyzed.

Results: The average TS before TACE was 40.1±14.36 kPa, and the average TS 1 month after TACE was 19.3±9.80 kPa. The mean progression-free survival (PFS) was 39.129 months, and the 1-, 3-, and 5-year PFS rates were 81.0%, 56.9%, and 37.9%, respectively. The mean overall survival (OS) was 48.552 months, and the 1-, 3-, and 5-year OS rates of patients with malignant hepatic tumors were 95.7%, 75.0%, and 49.1%, respectively. Tumor number, tumor location, TS before TACE, and TS 1 month after TACE were significant predictive factors for OS (P=0.02, P=0.03, P<0.001, and P<0.001, respectively). Rank correlation analysis and linear regression revealed that a higher TS before or 1 month after TACE was negatively associated with PFS. The reduction ratio in TS before and 1 month after therapy was positively associated with PFS. The optimal cutoff TS value was set at 46 and 24.5 kPa before and 1 month after TACE according to the optimal Youden index. Kaplan-Meier survival analyses demonstrated that the 2 groups had significant differences in OS and PFS and that a higher TS was positively correlated with OS and PFS.

Conclusions: Our results verify that US-E provides additional information to characterize the tumoral stiffness of HCC. These findings indicate that US-E is a valuable tool for evaluating the tumor response after TACE therapy in patients. TS can also be an independent prognostic factor. Patients with a high TS had a higher risk of recurrence and a worse survival time.

Keywords: Ultrasound elastography (US-E); hepatocellular carcinoma (HCC); transarterial chemoembolization (TACE).

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-292/coif). The authors have no conflicts of interest to declare.

2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.

Figures

Figure 1
Figure 1
A flow diagram of the case selection procedure. HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; US-E, ultrasound elasticity.
Figure 2
Figure 2
TS measurement using ultrasound elastography US-E. (A) The US-E measurement result of a local tumor before TACE demonstrated a TS value of 50 kPa. (B) The US-E measurement result of a local tumor before TACE demonstrated a TS value of 72 kPa. (C) The US-E measurement result of a local tumor before TACE demonstrated a TS value of 25.2 kPa. TS, tumor stiffness; TACE, transarterial chemoembolization; US-E, ultrasound elasticity.
Figure 3
Figure 3
Rank correlation analysis and linear regression analysis of the relationship between TS and PFS 5 years after TACE. (A,B) The relationship between TS before and 1 month after TACE, and PFS within 5 years after TACE. Rank correlation analysis revealed that a higher TS before and 1 month after TACE was negatively correlated with PFS (r=–0.807, r=–0.912; P

Figure 4

Kaplan-Meier analysis in all included…

Figure 4

Kaplan-Meier analysis in all included patients and comparison of the PFS according to…

Figure 4
Kaplan-Meier analysis in all included patients and comparison of the PFS according to TS. (A) Mean PFS was 39.129 months (95% CI: 35.407–42.852). The 1-, 3-, and 5-year PFS rates of patients with hepatic malignant tumors were 81.0%, 56.9%, and 37.9%, respectively. (B) Comparison of PFS in the patients with low TS ≤46 kPa and those with high TS >46 kPa. (C) Comparison of PFS in the patients with TS ≤24.5 kPa and those with high TS >24.5 kPa. PFS, progression-free survival; TS, tumor stiffness.

Figure 5

Kaplan-Meier analysis in all included…

Figure 5

Kaplan-Meier analysis in all included patients and comparison of the OS according to…

Figure 5
Kaplan-Meier analysis in all included patients and comparison of the OS according to TS. (A) Mean OS was 48.552 months (95% CI: 45.688–51.415). The 1-, 3-, and 5-year OS of patients with hepatic malignant tumors was 95.7%, 75.0%, and 49.1%, respectively. (B) Comparison of OS in the patients with low TS ≤46 kPa and those with high TS >46 kPa. (C) Comparison of OS in the patients with TS ≤24.5 kPa and those with TS >24.5 kPa. OS, overall survival; TS, tumor stiffness.
Figure 4
Figure 4
Kaplan-Meier analysis in all included patients and comparison of the PFS according to TS. (A) Mean PFS was 39.129 months (95% CI: 35.407–42.852). The 1-, 3-, and 5-year PFS rates of patients with hepatic malignant tumors were 81.0%, 56.9%, and 37.9%, respectively. (B) Comparison of PFS in the patients with low TS ≤46 kPa and those with high TS >46 kPa. (C) Comparison of PFS in the patients with TS ≤24.5 kPa and those with high TS >24.5 kPa. PFS, progression-free survival; TS, tumor stiffness.
Figure 5
Figure 5
Kaplan-Meier analysis in all included patients and comparison of the OS according to TS. (A) Mean OS was 48.552 months (95% CI: 45.688–51.415). The 1-, 3-, and 5-year OS of patients with hepatic malignant tumors was 95.7%, 75.0%, and 49.1%, respectively. (B) Comparison of OS in the patients with low TS ≤46 kPa and those with high TS >46 kPa. (C) Comparison of OS in the patients with TS ≤24.5 kPa and those with TS >24.5 kPa. OS, overall survival; TS, tumor stiffness.

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. 10.3322/caac.21660
    1. Bruix J, Sherman M, American Association for the Study of Liver Diseases . Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2. 10.1002/hep.24199
    1. Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, et al. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021;10:181-223. 10.1159/000514174
    1. Peisen F, Maurer M, Grosse U, Nikolaou K, Syha R, Ketelsen D, Artzner C, Bitzer M, Horger M, Grözinger G. Predictive performance of the mHAP-II score in a real-life western cohort with hepatocellular carcinoma following trans-arterial chemoembolisation with drug-eluting beads (DEB-TACE). Eur Radiol 2020;30:3782-92. 10.1007/s00330-020-06734-8
    1. Wang Q, Xia D, Bai W, Wang E, Sun J, Huang M, et al. Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study. J Hepatol 2019;70:893-903. 10.1016/j.jhep.2019.01.013
    1. Zhao P, Zhao J, Deng Y, Zeng G, Jiang Y, Liao L, Zhang S, Tao Q, Liu Z, Tang X, Tu X, Jiang L, Zhang H, Zheng Y. Application of iron/barium ferrite/carbon-coated iron nanocrystal composites in transcatheter arterial chemoembolization of hepatocellular carcinoma. J Colloid Interface Sci 2021;601:30-41. 10.1016/j.jcis.2021.05.102
    1. Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg 2015;261:947-55. 10.1097/SLA.0000000000000710
    1. Crocetti L, Della Pina C, Cioni D, Lencioni R. Peri-intraprocedural imaging: US, CT, and MRI. Abdom Imaging 2011;36:648-60. 10.1007/s00261-011-9750-9
    1. Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, Charboneau JW, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update. Radiology 2014;273:241-60. 10.1148/radiol.14132958
    1. Li B, Zhao X, Wang Q, Jing H, Shao H, Zhang L, Cheng W. Prediction of high nodal burden in invasive breast cancer by quantitative shear wave elastography. Quant Imaging Med Surg 2022;12:1336-47. 10.21037/qims-21-580
    1. Lupsor-Platon M, Serban T, Silion AI, Tirpe A, Florea M. Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: A Step Forward for Better Evaluation Using Ultrasound Elastography. Cancers (Basel) 2020.
    1. Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, Cosgrove D, Ferraioli G, Friedrich-Rust M, Gilja OH, Goertz RS, Karlas T, de Knegt R, de Ledinghen V, Piscaglia F, Procopet B, Saftoiu A, Sidhu PS, Sporea I, Thiele M. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med 2017;38:e48. 10.1055/a-0641-0076
    1. Ferraioli G, Filice C, Castera L, Choi BI, Sporea I, Wilson SR, et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3: liver. Ultrasound Med Biol 2015;41:1161-79. 10.1016/j.ultrasmedbio.2015.03.007
    1. European Association for the Study of the Liver. Clinical Practice Guideline Panel ; EASL Governing Board. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021;75:659-89. 10.1016/j.jhep.2021.05.025
    1. Srinivasa Babu A, Wells ML, Teytelboym OM, Mackey JE, Miller FH, Yeh BM, Ehman RL, Venkatesh SK. Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and Future Directions. Radiographics 2016;36:1987-2006. 10.1148/rg.2016160042
    1. Sarvazyan A, Hall TJ, Urban MW, Fatemi M, Aglyamov SR, Garra BS. AN. OVERVIEW OF ELASTOGRAPHY - AN EMERGING BRANCH OF MEDICAL IMAGING. Curr Med Imaging Rev 2011;7:255-82. 10.2174/157340511798038684
    1. Sigrist RMS, Liau J, Kaffas AE, Chammas MC, Willmann JK. Ultrasound Elastography: Review of Techniques and Clinical Applications. Theranostics 2017;7:1303-29. 10.7150/thno.18650
    1. Wang XP, Wang Y, Ma H, Wang H, Yang DW, Zhao XY, Jin EH, Yang ZH. Assessment of liver fibrosis with liver and spleen magnetic resonance elastography, serum markers in chronic liver disease. Quant Imaging Med Surg 2020;10:1208-22. 10.21037/qims-19-849
    1. Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol 2016;22:7236-51. 10.3748/wjg.v22.i32.7236
    1. Ferraioli G, Wong VW, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. Ultrasound Med Biol 2018;44:2419-40. 10.1016/j.ultrasmedbio.2018.07.008
    1. Grgurevic I, Bokun T, Salkic NN, Brkljacic B, Vukelić-Markovic M, Stoos-Veic T, Aralica G, Rakic M, Filipec-Kanizaj T, Berzigotti A. Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions. Liver Int 2018;38:1055-63. 10.1111/liv.13611
    1. Wu S, Zeng N, Sun F, Zhou J, Wu X, Sun Y, Wang B, Zhan S, Kong Y, Jia J, You H, Yang HI. Hepatocellular Carcinoma Prediction Models in Chronic Hepatitis B: A Systematic Review of 14 Models and External Validation. Clin Gastroenterol Hepatol 2021;19:2499-513. 10.1016/j.cgh.2021.02.040
    1. Dawood RM, Salum GM, El-Meguid MA, Elsayed A, Yosry A, Abdelaziz A, Shousha HI, Nabeel MM, El Awady MK. Development of a gene signature for predicting cirrhosis risk score of chronic liver disease associated with HCV infection in Egyptians. Microb Pathog 2021;153:104805. 10.1016/j.micpath.2021.104805
    1. Park Y, Kim SU, Kim BK, Park JY, Kim DY, Ahn SH, Park YE, Park JH, Lee YI, Yun HR, Han KH. Addition of tumor multiplicity improves the prognostic performance of the hepatoma arterial-embolization prognostic score. Liver Int 2016;36:100-7. 10.1111/liv.12878
    1. Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology 2018;154:1706-1718.e1. 10.1053/j.gastro.2018.01.064
    1. Kadalayil L, Benini R, Pallan L, O'Beirne J, Marelli L, Yu D, Hackshaw A, Fox R, Johnson P, Burroughs AK, Palmer DH, Meyer T. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol 2013;24:2565-70. 10.1093/annonc/mdt247
    1. Park SJ, Yoon JH, Lee DH, Lim WH, Lee JM. Tumor Stiffness Measurements on MR Elastography for Single Nodular Hepatocellular Carcinomas Can Predict Tumor Recurrence After Hepatic Resection. J Magn Reson Imaging 2021;53:587-96. 10.1002/jmri.27359
    1. Vogl TJ, Mack MG, Balzer JO, Engelmann K, Straub R, Eichler K, Woitaschek D, Zangos S. Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy. Radiology 2003;229:457-64. 10.1148/radiol.2292021329
    1. Gerber L, Fitting D, Srikantharajah K, Weiler N, Kyriakidou G, Bojunga J, Schulze F, Bon D, Zeuzem S, Friedrich-Rust M. Evaluation of 2D- Shear Wave Elastography for Characterisation of Focal Liver Lesions. J Gastrointestin Liver Dis 2017;26:283-90. 10.15403/jgld.2014.1121.263.dsh
    1. Guibal A, Boularan C, Bruce M, Vallin M, Pilleul F, Walter T, Scoazec JY, Boublay N, Dumortier J, Lefort T. Evaluation of shearwave elastography for the characterisation of focal liver lesions on ultrasound. Eur Radiol 2013;23:1138-49. 10.1007/s00330-012-2692-y

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