PDF icon Download PDF
Open Access
CC BY-NC-ND 4.0 · Indian J Radiol Imaging 2015; 25(02): 121-128
DOI: 10.4103/0971-3026.155835
Imaging in Oncology: Recent Advances

Imaging for assessment of treatment response in hepatocellular carcinoma: Current update

Koichi Hayano
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
,
Sang Ho Lee
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
,
Dushyant V Sahani
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
› Author Affiliations
› Further Information
Also available ateRefMedOne
 PDF Download Permissions and Reprints
Preview

Abstract

Morphologic methods such as the Response Evaluation Criteria in Solid Tumors (RECIST) are considered as the gold standard for response assessment in the management of cancer. However, with the increasing clinical use of antineoplastic cytostatic agents and locoregional interventional therapies in hepatocellular carcinoma (HCC), conventional morphologic methods are confronting limitations in response assessment. Thus, there is an increasing interest in new imaging methods for response assessment, which can evaluate tumor biology such as vascular physiology, fibrosis, necrosis, and metabolism. In this review, we discuss various novel imaging methods for response assessment and compare them with the conventional ones in HCC.

Keywords

Computed tomography perfusion - diffusion weighted imaging - amic contrast-enhanced magnetic resonance imaging - hepatocellular carcinoma - positron emission tomography


Publication History

Article published online:
30 July 2021

© 2015. Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Zhu AX, Duda DG, Sahani DV, Jain RK. HCC and angiogenesis: Possible targets and future directions. Nat Rev Clin Oncol 2011;8:292-301.
  • 2 Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693-9.
  • 3 Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.
  • 4 Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34.
  • 5 Cheng A, Kang Y, Lin D, Park J, Kudo M, Qin S, et al. Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC). J Clin Oncol 2011;29(Suppl):abstr 4000.
  • 6 Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: A comprehensive report of long-term outcomes. Gastroenterology 2010;138:52-64.
  • 7 Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: Chemoembolization versus radioembolization. Am J Transplant 2009;9:1920-8.
  • 8 Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al.; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet 2002;359:1734-9.
  • 9 Cho YK, Rhim H, Noh S. Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: A systematic review. J Gastroenterol Hepatol 2011;26:1354-60.
  • 10 Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-16.
  • 11 Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New response evaluation criteria in solid tumors (RECIST) guidelines for advanced non-small cell lung cancer: Comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8.
  • 12 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
  • 13 Yaghmai V, Miller FH, Rezai P, Benson AB 3 rd , Salem R. Response to treatment series: Part 2, tumor response assessment--using new and conventional criteria. AJR Am J Roentgenol 2011;197:18-27.
  • 14 Murakami T, Imai Y, Okada M, Hyodo T, Lee WJ, Kim MJ, et al. Ultrasonography, computed tomography and magnetic resonance imaging of hepatocellular carcinoma: Toward improved treatment decisions. Oncology 2011;81(Suppl 1):86-99.
  • 15 Taylor M, Rossler J, Geoerger B, Vassal G, Farace F. New anti-angiogenic strategies in pediatric solid malignancies: Agents and biomarkers of a near future. Expert Opin Investig Drugs 2010;19:859-74.
  • 16 Hennedige T, Venkatesh SK. Imaging of hepatocellular carcinoma: Diagnosis, staging and treatment monitoring. Cancer Imaging 2013;12:530-47.
  • 17 Shields AF. Positron emission tomography measurement of tumor metabolism and growth: Its expanding role in oncology. Mol Imaging Biol 2006;8:141-50.
  • 18 Hayano K, Fuentes-Orrego JM, Sahani DV. New approaches for precise response evaluation in hepatocellular carcinoma. World J Gastroenterol 2014;20:3059-68.
  • 19 Jiang T, Zhu AX, Sahani DV. Established and novel imaging biomarkers for assessing response to therapy in hepatocellular carcinoma. J Hepatol 2013;58:169-77.
  • 20 Gillmore R, Stuart S, Kirkwood A, Hameeduddin A, Woodward N, Burroughs AK, et al. EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 2011;55:1309-16.
  • 21 Forner A, Ayuso C, Varela M, Rimola J, Hessheimer AJ, de Lope CR, et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: Are response evaluation criteria in solid tumors reliable? Cancer 2009;115:616-23.
  • 22 Welsh JL, Bodeker K, Fallon E, Bhatia SK, Buatti JM, Cullen JJ. Comparison of response evaluation criteria in solid tumors with volumetric measurements for estimation of tumor burden in pancreatic adenocarcinoma and hepatocellular carcinoma. Am J Surg 2012;204:580-5.
  • 23 Sohaib SA, Turner B, Hanson JA, Farquharson M, Oliver RT, Reznek RH. CT assessment of tumour response to treatment: Comparison of linear, cross-sectional and volumetric measures of tumour size. Br J Radiol 2000;73:1178-84.
  • 24 Zhu AX, Holalkere NS, Muzikansky A, Horgan K, Sahani DV. Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma. Oncologist 2008;13:120-5.
  • 25 Jiang T, Kambadakone A, Kulkarni NM, Zhu AX, Sahani DV. Monitoring response to antiangiogenic treatment and predicting outcomes in advanced hepatocellular carcinoma using image biomarkers, CT perfusion, tumor density, and tumor size (RECIST). Invest Radiol 2012;47:11-7.
  • 26 Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: A phase II study. J Clin Oncol 2009;27:3027-35.
  • 27 Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24:4293-300.
  • 28 Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al.; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421-30.
  • 29 Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.
  • 30 Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al.; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100:698-711.
  • 31 Riaz A, Miller FH, Kulik LM, Nikolaidis P, Yaghmai V, Lewandowski RJ, et al. Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA 2010;303:1062-9.
  • 32 Prajapati HJ, Spivey JR, Hanish SI, El-Rayes BF, Kauh JS, Chen Z, et al. 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 2013;24:965-73.
  • 33 Edeline J, Boucher E, Rolland Y, Vauléon E, Pracht M, Perrin C, et al. Comparison of tumor response by response evaluation criteria in solid tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 2012;118:147-56.
  • 34 Shim JH, Lee HC, Kim SO, Shin YM, Kim KM, Lim YS, et al. Which response criteria best help predict survival of patients with hepatocellular carcinoma following chemoembolization? A validation study of old and new models. Radiology 2012;262:708-18.
  • 35 Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: Proposal of new computed tomography response criteria. J Clin Oncol 2007;25:1753-9.
  • 36 Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, Johnson MM, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: A quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 2004;183:1619-28.
  • 37 Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL, et al. We should desist using RECIST, at least in GIST. J Clin Oncol 2007;25:1760-4.
  • 38 Faivre S, Zappa M, Vilgrain V, Boucher E, Douillard JY, Lim HY, et al. Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clin Cancer Res 2011;17:4504-12.
  • 39 Aoyagi T, Shuto K, Okazumi S, Hayano K, Satoh A, Saitoh H, et al. Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis. Eur Radiol 2012;22:1172-7.
  • 40 Goh V, Sarker D, Osmany S, Cook GJ. Functional imaging techniques in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2012;39:1070-9.
  • 41 Padhani AR, Liu G, Koh DM, Chenevert TL, Thoeny HC, Takahara T, et al. Diffusion-weighted magnetic resonance imaging as a cancer biomarker: Consensus and recommendations. Neoplasia 2009;11:102-25.
  • 42 Kamel IR, Bluemke DA, Ramsey D, Abusedera M, Torbenson M, Eng J, et al. Role of diffusion-weighted imaging in estimating tumor necrosis after chemoembolization of hepatocellular carcinoma. AJR Am J Roentgenol 2003;181:708-10.
  • 43 Goshima S, Kanematsu M, Kondo H, Yokoyama R, Tsuge Y, Shiratori Y, et al. Evaluating local hepatocellular carcinoma recurrence post-transcatheter arterial chemoembolization: Is diffusion-weighted MRI reliable as an indicator? J Magn Reson Imaging 2008;27:834-9.
  • 44 Chen CY, Li CW, Kuo YT, Jaw TS, Wu DK, Jao JC, et al. Early response of hepatocellular carcinoma to transcatheter arterial chemoembolization: Choline levels and MR diffusion constants--initial experience. Radiology 2006;239:448-56.
  • 45 Yuan Z, Ye XD, Dong S, Xu LC, Xu XY, Liu SY, et al. Role of magnetic resonance diffusion-weighted imaging in evaluating response after chemoembolization of hepatocellular carcinoma. Eur J Radiol 2010;75:e9-14.
  • 46 Schraml C, Schwenzer NF, Martirosian P, Bitzer M, Lauer U, Claussen CD, et al. Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib treatment: Initial results. AJR Am J Roentgenol 2009;193:W301-7.
  • 47 Lewin M, Fartoux L, Vignaud A, Arrivé L, Menu Y, Rosmorduc O. The diffusion-weighted imaging perfusion fraction f is a potential marker of sorafenib treatment in advanced hepatocellular carcinoma: A pilot study. Eur Radiol 2011;21:281-90.
  • 48 Sahani DV, Jiang T, Hayano K, Duda DG, Catalano OA, Ancukiewicz M, et al. Magnetic resonance imaging biomarkers in hepatocellular carcinoma: Association with response and circulating biomarkers after sunitinib therapy. J Hematol Oncol 2013;6:51.
  • 49 Dale BM, Braithwaite AC, Boll DT, Merkle EM. Field strength and diffusion encoding technique affect the apparent diffusion coefficient measurements in diffusion-weighted imaging of the abdomen. Invest Radiol 2010;45:104-8.
  • 50 Ogura A, Hayakawa K, Miyati T, Maeda F. Imaging parameter effects in apparent diffusion coefficient determination of magnetic resonance imaging. Eur J Radiol 2011;77:185-8.
  • 51 Marcus CD, Ladam-Marcus V, Cucu C, Bouché O, Lucas L, Hoeffel C. Imaging techniques to evaluate the response to treatment in oncology: Current standards and perspectives. Crit Rev Oncol Hematol 2009;72:217-38.
  • 52 Miles KA. Perfusion CT for the assessment of tumour vascularity: Which protocol? Br J Radiol 2003;76:S36-42.
  • 53 Miles KA, Hayball M, Dixon AK. Colour perfusion imaging: A new application of computed tomography. Lancet 1991;337:643-5.
  • 54 Kambadakone AR, Sahani DV. Body perfusion CT: Technique, clinical applications, and advances. Radiol Clin North Am 2009;47:161-78.
  • 55 Chen G, Ma DQ, He W, Zhang BF, Zhao LQ. Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2008;14:5738-43.
  • 56 Yang L, Zhang XM, Tan BX, Liu M, Dong GL, Zhai ZH. Computed tomographic perfusion imaging for the therapeutic response of chemoembolization for hepatocellular carcinoma. J Comput Assist Tomogr 2012;36:226-30.
  • 57 Hayano K, Lee SH, Yoshida H, Zhu AX, Sahani DV. Fractal analysis of CT perfusion images for evaluation of antiangiogenic treatment and survival in hepatocellular carcinoma. Acad Radiol 2014;21:654-60.
  • 58 Hahn OM, Yang C, Medved M, Karczmar G, Kistner E, Karrison T, et al. Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma. J Clin Oncol 2008;26:4572-8.
  • 59 Flaherty KT, Rosen MA, Heitjan DF, Gallagher ML, Schwartz B, Schnall MD, et al. Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma. Cancer Biol Ther 2008;7:496-501.
  • 60 Hsu CY, Shen YC, Yu CW, Hsu C, Hu FC, Hsu CH, et al. Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil. J Hepatol 2011;55:858-65.
  • 61 Yau T, Chen PJ, Chan P, Curtis CM, Murphy PS, Suttle AB, et al. Phase I dose-finding study of pazopanib in hepatocellular carcinoma: Evaluation of early efficacy, pharmacokinetics, and pharmacodynamics. Clin Cancer Res 2011;17:6914-23.
  • 62 Lavini C, Verhoeff JJ. Reproducibility of the gadolinium concentration measurements and of the fitting parameters of the vascular input function in the superior sagittal sinus in a patient population. Magn Reson Imaging 2010;28:1420-30.
  • 63 Vlieger EJ, Lavini C, Majoie CB, den Heeten GJ. Reproducibility of functional MR imaging results using two different MR systems. AJNR Am J Neuroradiol 2003;24:652-7.
  • 64 Goh V, Halligan S, Hugill JA, Gartner L, Bartram CI. Quantitative colorectal cancer perfusion measurement using dynamic contrast-enhanced multidetector-row computed tomography: Effect of acquisition time and implications for protocols. J Comput Assist Tomogr 2005;29:59-63.
  • 65 Ng CS, Chandler AG, Wei W, Herron DH, Anderson EF, Kurzrock R, et al. Reproducibility of CT perfusion parameters in liver tumors and normal liver. Radiology 2011;260:762-70.
  • 66 Talbot JN, Gutman F, Fartoux L, Grange JD, Ganne N, Kerrou K, et al. PET/CT in patients with hepatocellular carcinoma using [(18) F] fluorocholine: Preliminary comparison with [(18) F] FDG PET/CT. Eur J Nucl Med Mol Imaging 2006;33:1285-9.
  • 67 Talbot JN, Fartoux L, Balogova S, Nataf V, Kerrou K, Gutman F, et al. Detection of hepatocellular carcinoma with PET/CT: A prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. J Nucl Med 2010;51:1699-706.
  • 68 Yamamoto Y, Nishiyama Y, Kameyama R, Okano K, Kashiwagi H, Deguchi A, et al. Detection of hepatocellular carcinoma using 11C-choline PET: Comparison with 18F-FDG PET. J Nucl Med 2008;49:1245-8.
  • 69 Park JW, Kim JH, Kim SK, Kang KW, Park KW, Choi JI, et al. A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med 2008;49:1912-21.
  • 70 Ho CL, Chen S, Yeung DW, Cheng TK. Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma. J Nucl Med 2007;48:902-9.
  • 71 Ho CL, Yu SC, Yeung DW. 11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. J Nucl Med 2003;44:213-21.
  • 72 Hwang KH, Choi DJ, Lee SY, Lee MK, Choe W. Evaluation of patients with hepatocellular carcinomas using [(11) C] acetate and [(18) F] FDG PET/CT: A preliminary study. Appl Radiat Isot 2009;67:1195-8.
  • 73 Salem N, Kuang Y, Corn D, Erokwu B, Kolthammer JA, Tian H, et al. (Methyl) 1-(11) c]-acetate metabolism in hepatocellular carcinoma. Mol Imaging Biol 2011;13:140-51.
  • 74 Yun M, Bang SH, Kim JW, Park JY, Kim KS, Lee JD. The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma. J Nucl Med 2009;50:1222-8.
  • 75 Salem N, Kuang Y, Wang F, Maclennan GT, Lee Z. PET imaging of hepatocellular carcinoma with 2-deoxy-2[18F] fluoro-D-glucose, 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and [N-methyl-11C]-choline. Q J Nucl Med Mol Imaging. 2009;53:144-56.
  • 76 Eckel F, Herrmann K, Schmidt S, Hillerer C, Wieder HA, Krause BJ, et al. Imaging of proliferation in hepatocellular carcinoma with the in vivo marker 18F-fluorothymidine. J Nucl Med 2009;50:1441-7.
  • 77 Song MJ, Bae SH, Yoo IeR, Park CH, Jang JW, Chun HJ, et al. Predictive value of 18 F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma. World J Gastroenterol 2012;18:3215-22.
  • 78 Torizuka T, Tamaki N, Inokuma T, Magata Y, Yonekura Y, Tanaka A, et al. Value of fluorine-18-FDG-PET to monitor hepatocellular carcinoma after interventional therapy. J Nucl Med 1994;35:1965-9.
  • 79 Kuehl H, Stattaus J, Hertel S, Hunold P, Kaiser G, Bockisch A, et al. Mid-term outcome of positron emission tomography/computed tomography-assisted radiofrequency ablation in primary and secondary liver tumours--a single-centre experience. Clin Oncol (R Coll Radiol) 2008;20:234-40.
  • 80 Kim BK, Kang WJ, Kim JK, Seong J, Park JY, Kim do Y, et al. 18F-fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma. Cancer 2011;117:4779-87.
  • 81 Takayasu K, Arii S, Matsuo N, Yoshikawa M, Ryu M, Takasaki K, et al. Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. AJR Am J Roentgenol 2000;175:699-704.
  • 82 Guan YS, Sun L, Zhou XP, Li X, Zheng XH. Hepatocellular carcinoma treated with interventional procedures: CT and MRI follow-up. World J Gastroenterol 2004;10:3543-8.
  • 83 Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991;32:623-50.
  • 84 Okazumi S, Isono K, Enomoto K, Kikuchi T, Ozaki M, Yamamoto H, et al. Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: Characterization of tumor and assessment of effect of treatment. J Nucl Med 1992;33:333-9.
  • 85 Khan MA, Combs CS, Brunt EM, Lowe VJ, Wolverson MK, Solomon H, et al. Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol 2000;32:792-7.