Abstract
Purpose
To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC).
Methods
This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss’ multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan–Meier and Cox proportional hazard model analyses.
Results
A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42–0.57), and substantial for mRECIST-target (κ range 0.62–0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35).
Conclusion
Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.
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References
Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul J-L, Schirmacher P, Vilgrain V (2018) EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 69 (1):182-236. https://doi.org/10.1016/j.jhep.2018.03.019
Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK (2018) Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 68 (2):723-750. https://doi.org/10.1002/hep.29913
Omata M, Cheng A-L, Kokudo N, Kudo M, Lee JM, Jia J, Tateishi R, Han K-H, Chawla YK, Shiina S, Jafri W, Payawal DA, Ohki T, Ogasawara S, Chen P-J, Lesmana CRA, Lesmana LA, Gani RA, Obi S, Dokmeci AK, Sarin SK (2017) Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11 (4):317-370. https://doi.org/10.1007/s12072-017-9799-9
Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, Benhamou Y, Avajon Y, Gruenberger T, Pomoni M, Langenberger H, Schuchmann M, Dumortier J, Mueller C, Chevallier P, Lencioni R (2010) Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study. Cardiovasc Intervent Radiol 33 (1):41-52. https://doi.org/10.1007/s00270-009-9711-7
Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M, Ayuso C, Castells L, Montañá X, Llovet JM, Bruix J (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmacokinetics. J Hepatol 46 (3):474-481. https://doi.org/10.1016/j.jhep.2006.10.020
Vincenzi B, Di Maio M, Silletta M, D’Onofrio L, Spoto C, Piccirillo MC, Daniele G, Comito F, Maci E, Bronte G, Russo A, Santini D, Perrone F, Tonini G (2015) Prognostic Relevance of Objective Response According to EASL Criteria and mRECIST Criteria in Hepatocellular Carcinoma Patients Treated with Loco-Regional Therapies: A Literature-Based Meta-Analysis. 10 (7):e0133488. https://doi.org/10.1371/journal.pone.0133488
Lencioni R, Montal R, Torres F, Park J-W, Decaens T, Raoul J-L, Kudo M, Chang C, Ríos J, Boige V, Assenat E, Kang Y-K, Lim H-Y, Walters I, Llovet JM (2017) Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC. J Hepatol 66 (6):1166-1172. https://doi.org/10.1016/j.jhep.2017.01.012
Yopp AC, Mansour JC, Beg MS, Arenas J, Trimmer C, Reddick M, Pedrosa I, Khatri G, Yakoo T, Meyer JJ, Shaw J, Marrero JA, Singal AG (2014) Establishment of a Multidisciplinary Hepatocellular Carcinoma Clinic is Associated with Improved Clinical Outcome. Ann Surg Oncol 21 (4):1287-1295. https://doi.org/10.1245/s10434-013-3413-8
Llovet JM, Fuster J, Bruix J (2004) The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 10 (S2):S115-S120. https://doi.org/10.1002/lt.20034
Jin B, Wang D, Lewandowski RJ, Riaz A, Ryu RK, Sato KT, Larson AC, Salem R, Omary RA (2011) Chemoembolization Endpoints: Effect on Survival Among Patients With Hepatocellular Carcinoma. American Journal of Roentgenology 196 (4):919-928. https://doi.org/10.2214/ajr.10.4770
Shropshire EL, Chaudhry M, Miller CM, Allen BC, Bozdogan E, Cardona DM, King LY, Janas GL, Do RK, Kim CY, Ronald J, Bashir MR (2019) LI-RADS Treatment Response Algorithm: Performance and Diagnostic Accuracy. Radiology 292 (1):226-234. https://doi.org/10.1148/radiol.2019182135
Chaudhry M, McGinty KA, Mervak B, Lerebours R, Li C, Shropshire E, Ronald J, Commander L, Hertel J, Luo S, Bashir MR, Burke LMB (2020) The LI-RADS Version 2018 MRI Treatment Response Algorithm: Evaluation of Ablated Hepatocellular Carcinoma. Radiology 294 (2):320-326. https://doi.org/10.1148/radiol.2019191581
Kim SW, Joo I, Kim H-C, Ahn SJ, Kang H-J, Jeon SK, Lee JM (2020) LI-RADS treatment response categorization on gadoxetic acid-enhanced MRI: diagnostic performance compared to mRECIST and added value of ancillary features. Eur Radiol. https://doi.org/10.1007/s00330-019-06623-9
Thibodeau-Antonacci A, Petitclerc L, Gilbert G, Bilodeau L, Olivié D, Cerny M, Castel H, Turcotte S, Huet C, Perreault P, Soulez G, Chagnon M, Kadoury S, Tang A (2019) Dynamic contrast-enhanced MRI to assess hepatocellular carcinoma response to Transarterial chemoembolization using LI-RADS criteria: A pilot study. Magn Reson Imaging 62:78-86. https://doi.org/10.1016/j.mri.2019.06.017
Seo N, Kim MS, Park M-S, Choi J-Y, Do RKG, Han K, Kim M-J (2019) Evaluation of treatment response in hepatocellular carcinoma in the explanted liver with Liver Imaging Reporting and Data System version 2017. Eur Radiol. https://doi.org/10.1007/s00330-019-06376-5
Zhang Y, Wang J, Li H, Zheng T, Jiang H, Li M, Song B (2020) Performance of LI-RADS version 2018 CT treatment response algorithm in tumor response evaluation and survival prediction of patients with single hepatocellular carcinoma after radiofrequency ablation. Annals of Translational Medicine 8 (6):388-388. https://doi.org/10.21037/atm.2020.03.120
Davenport MS, Khalatbari S, Liu PSC, Maturen KE, Kaza RK, Wasnik AP, Al-Hawary MM, Glazer DI, Stein EB, Patel J, Somashekar DK, Viglianti BL, Hussain HK (2014) Repeatability of Diagnostic Features and Scoring Systems for Hepatocellular Carcinoma by Using MR Imaging. 272 (1):132-142. https://doi.org/10.1148/radiol.14131963
Barth BK, Donati OF, Fischer MA, Ulbrich EJ, Karlo CA, Becker A, Seifert B, Reiner CS (2016) Reliability, Validity, and Reader Acceptance of LI-RADS—An In-depth Analysis. 23 (9):1145-1153. https://doi.org/10.1016/j.acra.2016.03.014
Yokoo T, Singal AG, Diaz De Leon A, Ananthakrishnan L, Fetzer DT, Pedrosa I, Khatri G (2020) Prevalence and clinical significance of discordant LI-RADS® observations on multiphase contrast-enhanced MRI in patients with cirrhosis. Abdominal Radiology 45 (1):177-187. https://doi.org/10.1007/s00261-019-02133-w
Prajapati HJ, Spivey JR, Hanish SI, El-Rayes BF, Kauh JS, Chen Z, Kim HS (2013) mRECIST and EASL responses at early time point by contrast-enhanced dynamic MRI predict survival in patients with unresectable hepatocellular carcinoma (HCC) treated by doxorubicin drug-eluting beads transarterial chemoembolization (DEB TACE). Ann Oncol 24 (4):965-973. https://doi.org/10.1093/annonc/mds605
Reig M, Rimola J, Torres F, Darnell A, Rodriguez-Lope C, Forner A, Llarch N, Ríos J, Ayuso C, Bruix J (2013) Postprogression survival of patients with advanced hepatocellular carcinoma: Rationale for second-line trial design. Hepatology 58 (6):2023-2031. https://doi.org/10.1002/hep.26586
De La Torre-Aláez M, Jordán-Iborra C, Casadei-Gardini A, Bilbao JI, Rodriguez-Fraile M, Sancho L, D’Avola D, Herrero JI, Iñarrairaegui M, Sangro B (2020) The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT. Cardiovasc Intervent Radiol. https://doi.org/10.1007/s00270-020-02444-2De La Torre-Aláez M, Jordán-Iborra C, Casadei-Gardini A, Bilbao JI, Rodriguez-Fraile M, Sancho L, D’Avola D, Herrero JI, Iñarrairaegui M, Sangro B (2020) The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT. Cardiovasc Intervent Radiol. https://doi.org/10.1007/s00270-020-02444-2
Park S, Joo I, Lee DH, Bae JS, Yoo J, Kim SW, Lee JM (2020) Diagnostic Performance of LI-RADS Treatment Response Algorithm for Hepatocellular Carcinoma: Adding Ancillary Features to MRI Compared with Enhancement Patterns at CT and MRI. Radiology 296 (3):554-561. https://doi.org/10.1148/radiol.2020192797
Seyal AR, Gonzalez-Guindalini FD, Arslanoglu A, Harmath CB, Lewandowski RJ, Salem R, Yaghmai V (2015) Reproducibility of mRECIST in assessing response to transarterial radioembolization therapy in hepatocellular carcinoma. Hepatology 62 (4):1111-1121. https://doi.org/10.1002/hep.27915
Choi MH, Park GE, Oh SN, Park MY, Rha SE, Lee YJ, Jung SE, Choi J-I (2018) Reproducibility of mRECIST in Measurement and Response Assessment for Hepatocellular Carcinoma Treated by Transarterial Chemoembolization. Acad Radiol 25 (11):1363-1373. https://doi.org/10.1016/j.acra.2018.02.013
Gillmore R, Stuart S, Kirkwood A, Hameeduddin A, Woodward N, Burroughs AK, Meyer T (2011) EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 55 (6):1309-1316. https://doi.org/10.1016/j.jhep.2011.03.007
Jung ES, Kim JH, Yoon EL, Lee HJ, Lee SJ, Suh SJ, Lee BJ, Seo YS, Yim HJ, Seo TS, Lee CH, Yeon JE, Park JJ, Kim JS, Bak YT, Byun KS (2013) Comparison of the methods for tumor response assessment in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. J Hepatol 58 (6):1181-1187. https://doi.org/10.1016/j.jhep.2013.01.039
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Drs. Singal and Yokoo are in part supported by NIH U01 C230694.
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Ali Pirasteh: GE Healthcare, institutional research support agreement (University of Wisconsin-Madison). Dr. Pirasteh has served as consultant on advisory board for Sanofi Genzyme. E. Aleks Sorra, Hector Marquez, Carson R. Sibley, Julia R. Fielding, Abhinav Vij, Nicole E. Rich, Ana Arroyo, Adam C. Yopp, Gaurav Khatri, Takeshi Yokoo: No disclosures. Amit G. Singal: Dr. Singal has served as consultant or on advisory boards for Bayer, Eisai, Genentech, BMS, Exelixis, AstraZeneca, Wako Diagnostics, Exact Sciences, Roche, Glycotest, GRAIL, and TARGET Pharmasolutions. Dr. Singal also serves on the LI-RADS Steering Committee.
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Pirasteh, A., Sorra, E.A., Marquez, H. et al. LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI. Abdom Radiol 46, 3708–3716 (2021). https://doi.org/10.1007/s00261-021-03043-6
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DOI: https://doi.org/10.1007/s00261-021-03043-6