Hepatocellular carcinoma (HCC) has a high incidence all over the world. Even if the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and could have a key role in clinical management. Since 1950 several radiological response criteria have been applied; however, it was not until 2000 that specific criteria for HCC were introduced by the European Association for the Study of the Liver (EASL), and these were then standardized in 2010 with the development of the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for HCC. The purpose of this brief review is to compare data in literature regarding the application and the performance of mRECIST in clinical practice, and to discuss unclear and open issues.

Keywords:

References

1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer127(12),2893–2917 (2010).
Medline CASGoogle Scholar
2 Sherman M. Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin. Liver Dis.30(1),3–16 (2010).
Medline CASGoogle Scholar
3 Cabibbo G, Craxì A. Hepatocellular cancer: optimal strategies for screening and surveillance. Dig. Dis.27(2),142–147 (2009).
MedlineGoogle Scholar
4 Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin. Liver Dis.19,329–333 (1999).
Medline CASGoogle Scholar
5 Sangro B, Carpanese L, Cianni R et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology54(3),868–878 (2011).
MedlineGoogle Scholar
6 Llovet JM, Ricci S, Mazzaferro V et al.; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med.359(4),378–390 (2008).
Medline CASGoogle Scholar
7 Cheng AL, Kang YK, Chen Z 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.10(1),25–34 (2009).
Medline CASGoogle Scholar
8 Agewall S, DeGroot E, Marcos-Alberca P et al. Ultrasound and radiology surrogate endpoints in pharmacological studies. Atherosclerosis224(1),12–24 (2012).
Medline CASGoogle Scholar
9 Memon K, Kulik L, Lewandowski RJ et al. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology141(2),526–535 (2011).
MedlineGoogle Scholar
10 Farber S, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N. Engl. J. Med.238(23),787–793 (1948).
Medline CASGoogle Scholar
11 Zubrod CG, Schneiderman M, Frei E 3rd et al. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. J. Chronic Disease Dis.11,7–33 (1960).
Google Scholar
12 WHO. WHO Handbook for Reporting Results of Cancer Treatment (Offset Publication No. 48). WHO, Geneva, Switzerland (1979).
Google Scholar
13 Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer47,207–214 (1981).
Medline CASGoogle Scholar
14 Therasse P. Measuring the clinical response. What does it mean? Eur. J. Cancer38(14),1817–1823 (2002).
Medline CASGoogle Scholar
15 Llovet JM, Real MI, Montaña X et al.; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet359(9319),1734–1739 (2002).
MedlineGoogle Scholar
16 Therasse P, Arbuck SG, Eisenhauer EA 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.92(3),205–216 (2000).
Medline CASGoogle Scholar
17 Therasse P, Eisenhauer EA, Verweij J. RECIST revisited: a review of validation studies on tumour assessment. Eur. J. Cancer42,1031–1039 (2006).
Medline CASGoogle Scholar
18 Eisenhauer EA, Therasse P et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version1.1). Eur. J. Cancer45(2),228–247 (2009).
Medline CASGoogle Scholar
19 Forner A, Ayuso C, Varela M et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer115(3),616–623 (2009).
MedlineGoogle Scholar
20 Kummar S, Gutierrez M, Doroshow JH, Murgo AJ. Drug development in oncology: classical cytotoxics and molecularly targeted agents. Br. J. Clin. Pharmacol.62(1),15–26 (2006).
Medline CASGoogle Scholar
21 Bruix J, Sherman M, Llovet JM 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.35(3),421–430 (2001).
Medline CASGoogle Scholar
22 Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology42(5),1208–1236 (2005).
MedlineGoogle Scholar
23 Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology53(3),1020–1022 (2011).
MedlineGoogle Scholar
24 Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin. Liver Dis.30,52–60 (2010).
Medline CASGoogle Scholar
25 Lovet JM, Di Bisceglie AM, Bruix J et al.; Panel of Experts in HCC–Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J. Natl Cancer Inst.100(10),698–711 (2008).
MedlineGoogle Scholar
26 Edeline J, Boucher E, Rolland Y 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. Cancer118(1),147–156 (2012).
Medline CASGoogle Scholar
27 Suzuki C, Torkzad MR, Jacobsson H et al. Interobserver and intraobserver variability in the response evaluation of cancer therapy according to RECIST and WHO-criteria. Acta Oncol.49(4),509–514 (2010).
MedlineGoogle Scholar
28 Erasmus JJ, Gladish GW, Broemeling L et al. Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J. Clin. Oncol.21(13),2574–2582 (2003).
MedlineGoogle Scholar
29 Bruix J, Reig M, Rimola J et al. Clinical decision making and research in hepatocellular carcinoma: pivotal role of imaging techniques. Hepatology54(6),2238–2244 (2011).
MedlineGoogle Scholar
30 Choi H, Charnsangavej C, Faria SC 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.25,1753–1759 (2007).
MedlineGoogle Scholar
31 Faivre S, Zappa M, Vilgrain V et al. Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clin. Cancer Res.17(13),4504–4512 (2011).
Medline CASGoogle Scholar
32 Lai CL, Wu PC, Chan GC et al. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer62(3),479–483 (1988).
Medline CASGoogle Scholar
33 Pelletier G, Roche A, Ink O et al. A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J. Hepatol.11(2),181–184 (1990).
Medline CASGoogle Scholar
34 Lai CL, Lau JY, Wu PC et al. Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology17(3),389–394 (1993).
Medline CASGoogle Scholar
35 Madden MV, Krige JE, Bailey S et al. Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma. Gut34(11),1598–1600 (1993).
Medline CASGoogle Scholar
36 Elba S, Giannuzzi V, Misciagna G et al. Randomized controlled trial of tamoxifen versus placebo in inoperable hepatocellular carcinoma. Ital. J. Gastroenterol.26(2),66–68 (1994).
Medline CASGoogle Scholar
37 Martínez Cerezo FJ, Tomás A, Donoso L et al. Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma. J. Hepatol.20(6),702–706 (1994).
Medline CASGoogle Scholar
38 A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. N. Engl. J. Med.332(19),1256–1261 (1995).
MedlineGoogle Scholar
39 Manesis EK, Giannoulis G, Zoumboulis P et al. Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: a randomized, controlled trial. Hepatology21(6),1535–1542 (1995).
Medline CASGoogle Scholar
40 Castells A, Bruix J, Brú C et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology109(3),917–922 (1995).
Medline CASGoogle Scholar
41 Bayraktar Y, Balkanci F, Kayhan B et al. A comparison of chemoembolization with conventional chemotherapy and symptomatic treatment in cirrhotic patients with hepatocellular carcinoma. Hepatogastroenterology43(9),681–687 (1996).
Medline CASGoogle Scholar
42 Kouroumalis E, Skordilis P, Thermos K et al. Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study. Gut42(3),442–447 (1998).
Medline CASGoogle Scholar
43 Riestra S, Rodriguez M, Delgado M et al. Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma. J. Clin. Gastroenterol.26(3),200–203 (1998).
Medline CASGoogle Scholar
44 Grimaldi C, Bleiberg H, Gay F et al. Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial. J. Clin. Oncol.16(2),411–417 (1998).
Medline CASGoogle Scholar
45 Bruix J, Llovet JM, Castells A et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatology27(6),1578–1583 (1998).
Medline CASGoogle Scholar
46 Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial. CLIP Group (Cancer of the Liver Italian Programme). Lancet352(9121),17–20 (1998).
MedlineGoogle Scholar
47 Chung YH, Song IH, Song BC et al. Combined therapy consisting of intraarterial cisplatin infusion and systemic interferon-alpha for hepatocellular carcinoma patients with major portal vein thrombosis or distant metastasis. Cancer88(9),1986–1991 (2000).
Medline CASGoogle Scholar
48 Llovet JM, Sala M, Castells L et al. Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology31(1),54–58 (2000).
Medline CASGoogle Scholar
49 Liu CL, Fan ST, Ng IO et al. Treatment of advanced hepatocellular carcinoma with tamoxifen and the correlation with expression of hormone receptors: a prospective randomized study. Am. J. Gastroenterol.95(1),218–222 (2000).
Medline CASGoogle Scholar
50 Villa E, Ferretti I, Grottola A et al. Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors. Br. J. Cancer84(7),881–885 (2001).
Medline CASGoogle Scholar
51 Ishikawa T, Ichida T, Sugitani S et al. Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma. J. Gastroenterol. Hepatol.16(4),452–459 (2001).
Medline CASGoogle Scholar
52 Lo CM, Ngan H, Tso WK et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology35(5),1164–1171 (2002).
Medline CASGoogle Scholar
53 Llovet JM, Real MI, Montaña X et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet359(9319),1734–1739 (2002).
MedlineGoogle Scholar
54 Yuen MF, Poon RT, Lai CL et al. A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. Hepatology36(3),687–691 (2002).
Medline CASGoogle Scholar
55 Chow PK, Tai BC, Tan CK et al. High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: a multicenter randomized controlled trial. Hepatology36(5),1221–1226 (2002).
Medline CASGoogle Scholar
56 Barbare JC, Bouché O, Bonnetain F et al. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J. Clin. Oncol.23(19),4338–4346 (2005).
Medline CASGoogle Scholar
57 Sarin SK, Kumar M, Garg S et al. High dose vitamin K3 infusion in advanced hepatocellular carcinoma. J. Gastroenterol. Hepatol.21(9),1478–1482 (2006).
Medline CASGoogle Scholar
58 Cammà C, Di Marco V, Orlando A et al. Treatment of hepatocellular carcinoma in compensated cirrhosis with radio-frequency thermal ablation (RFTA): a prospective study. J. Hepatol.42(4),535–540 (2005).
MedlineGoogle Scholar
59 Becker G, Allgaier HP, Olschewski M et al. Long-acting octreotide versus placebo for treatment of advanced HCC: a randomized controlled double-blind study. Hepatology45(1),9–15 (2007).
Medline CASGoogle Scholar
60 Dimitroulopoulos D, Xinopoulos D, Tsamakidis K et al. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial. World J. Gastroenterol.13(23),3164–3170 (2007).
Medline CASGoogle Scholar
61 Barbare JC, Bouché O, Bonnetain F et al. Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a Phase III multicentre, randomised, double blind placebo-controlled study. Eur. J. Cancer45(10),1788–1797 (2009).
Medline CASGoogle Scholar
62 Cabibbo G, Genco C, Di Marco V et al. Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation. Aliment Pharmacol. Ther.34(2),196–204 (2011).
Medline CASGoogle Scholar
63 Iavarone M, Cabibbo G, Piscaglia F et al.; SOFIA (SOraFenib Italian Assessment) study group. Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy. Hepatology54(6),2055–2063 (2011).
Medline CASGoogle Scholar
64 Gillmore R, Stuart S, Kirkwood A et al. EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J. Hepatol.55(6),1309–1316 (2011).
MedlineGoogle Scholar

Vol. 9, No. 6

Supplemental Materials

Metrics

Downloaded 212 times

History

Published online 29 May 2013

Published in print June 2013

Information

Keywords

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

PDF download

Assessment of treatment response in hepatocellular carcinoma: a review of the literature

Abstract

References