Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast‑enhanced ultrasonography: Preliminary result

Shiozawa,Kazue; Watanabe,Manabu; Ikehara,Takashi; Kogame,Michio; Kikuchi,Yoshinori; Igarashi,Yoshinori; Sumino,Yasukiyo

doi:10.3892/ol.2016.4669

Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast‑enhanced ultrasonography: Preliminary result

Authors:
- Kazue Shiozawa
- Manabu Watanabe
- Takashi Ikehara
- Michio Kogame
- Yoshinori Kikuchi
- Yoshinori Igarashi
- Yasukiyo Sumino
View Affiliations

Affiliations: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo 143‑8541, Japan
Published online on: June 1, 2016 https://doi.org/10.3892/ol.2016.4669
Pages: 579-584

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2‑4 weeks of treatment, and the images of the target lesion in the post‑vascular phase with a re‑injection method were analyzed. The presence (+) or absence (‑) of intratumoral necrosis and the intratumoral vascular architecture on micro‑flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non‑enhancement after re‑injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan‑Meier method and compared using the log rank test between the intratumoral necrosis (+) and (‑) groups, and among the Vd, Vnc and Vi groups. P<0.05 was considered to indicate a statistically significant difference. The number of patients in the intratumoral necrosis (+) and (‑) groups was 8 and 18 patients, respectively, and the median survival time (MST) was 7.2 months [95% confidence interval (CI), 2.2‑12.2] and 9.5 months (95% CI, 5.1‑13.8), respectively (P=0.44). The MFI findings were observed in 11 patients in the Vd group, 10 patients in the Vnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0‑23.3), 11.0 months (95% CI, 3.5‑17.6) and 3.6 months (95% CI: 1.2‑6.0), respectively. The P‑value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ and Lau WY: A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 243:321–328. 2006. View Article : Google Scholar : PubMed/NCBI
3	Yi HM, Zhang W, Ai X, Li KY and Deng YB: Radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma conforming to the Milan criteria: Systemic review and meta-analysis. Int J Clin Exp Med. 7:3150–3163. 2014.PubMed/NCBI
4	Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, et al: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI
5	Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, et al: Sorafenib (BAY 43–9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol. 59:561–574. 2007. View Article : Google Scholar : PubMed/NCBI
6	Hotte SJ and Hirte HW: BAY 43–9006: Early clinical data in patients with advanced solid malignancies. Curr Pharm Des. 8:2249–2253. 2002. View Article : Google Scholar : PubMed/NCBI
7	Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI
8	Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, 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. 10:25–34. 2009. View Article : Google Scholar : PubMed/NCBI
9	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
10	Lencioni R and Llovet JM: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30:52–60. 2010. View Article : Google Scholar : PubMed/NCBI
11	Kudo M, Kubo S, Takayasu K, Sakamoto M, Tanaka M, Ikai I, Furuse J, Nakamura K and Makuuchi M: Liver Cancer Study Group of Japan (Committee for Response Evaluation Criteria in Cancer of the Liver, Liver Cancer Study Group of Japan): Response evaluation criteria in cancer of the liver (RECICL) proposed by the liver cancer study group of Japan (2009 revised version). Hepatol Res. 40:686–692. 2010. View Article : Google Scholar : PubMed/NCBI
12	Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA and Benjamin RS: 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. View Article : Google Scholar : PubMed/NCBI
13	Watanabe M, Shiozawa K, Takahashi M, Wakui N, Otsuka Y, Kaneko H, Tanikawa K, Shibuya K, Kamiyama N and Sumino Y: Parametric imaging using contrast-enhanced ultrasound with Sonazoid for hepatocellular carcinoma. J Med Ultrasonics. 37:81–86. 2010. View Article : Google Scholar
14	Shiozawa K, Watanabe M, Kikuchi Y, Kudo T, Maruyama K and Sumino Y: Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced ultrasonography: A pilot study. World J Gastroenterol. 18:5753–5758. 2012. View Article : Google Scholar : PubMed/NCBI
15	Sugimoto K, Moriyasu F, Kamiyama N, Metoki R, Yamada M, Imai Y and Iijima H: Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast-enhanced sonography. Hepatol Res. 38:790–799. 2008. View Article : Google Scholar : PubMed/NCBI
16	Yang H, Liu GJ, Lu MD, Xu HX and Xie XY: Evaluation of the vascular archirecture of hepatocellular carcinoma by micro flow imaging: Pathologic correlation. J Ultrasound Med. 26:461–467. 2007.PubMed/NCBI
17	Linden RA, Trabulsi EJ, Forsberg F, Gittens PR, Gomella LG and Halpern EJ: Contrast enhanced ultrasound flash replenishment method for directed prostate biopsies. J Urol. 178:2354–2358. 2007. View Article : Google Scholar : PubMed/NCBI
18	Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC and Williams R: Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 60:646–649. 1973. View Article : Google Scholar : PubMed/NCBI
19	Kudo M: Hepatocellular carcinoma 2009 and beyond: From the surveillance to molecular targeted therapy. Oncology. 75(Suppl 1): 1–12. 2008. View Article : Google Scholar : PubMed/NCBI
20	Zhao H, Yao JL, Wang Y and Zhou KR: Detection of small hepatocellular carcinoma: Comparison of dynamic enhancement magnetic resonance imaging and multiphase multirow-detector helical CT scanning. World J Gastroenterol. 13:1252–1256. 2007. View Article : Google Scholar : PubMed/NCBI
21	Bruix J, Sala M and Llovet JM: Chemoembolization for hepatocellular carcinoma. Gastroenterology. 127(Suppl 1): S179–S188. 2004. View Article : Google Scholar : PubMed/NCBI
22	Moschouris H, Malagari K, Gkoutzios P, Kalokairinou M, Stamatiou K, Chatzimichail K, Kornezos I, Karagiannis E, Kiltenis M and Papadaki MG: Intermediate and advanced hepatocellular carcinoma treated with the antiangiogenic agent sorafenib. Evaluation with unenhanced and contrast-enhanced ultrasonography. Med Ultrason. 14:87–94. 2012.PubMed/NCBI
23	Tanaka H, Iijima H, Higashiura A, Yoh K, Ishii A, Takashima T, Sakai Y, Aizawa N, Iwata K, Ikeda N, et al: New malignant grading system for hepatocellular carcinoma using the Sonazoid contrast agent for ultrasonography. J Gastroenterol. 49:755–763. 2014. View Article : Google Scholar : PubMed/NCBI
24	Sato K, Tanaka S, Mitsunori Y, Mogushi K, Yasen M, Aihara A, Ban D, Ochiai T, Irie T, Kudo A, et al: Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: Clinical and biological significance. Hepatology. 57:1436–1447. 2013. View Article : Google Scholar : PubMed/NCBI
25	Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science. 307:58–62. 2005. View Article : Google Scholar : PubMed/NCBI
26	Matsui O, Kadoya M, Kameyama T, Yoshikawa J, Takashima T, Nakanuma Y, Unoura M, Kobayashi K, Izumi R and Ida M: Benign and malignant nodules in cirrhotic livers: Distinction based on blood supply. Radiology. 178:493–497. 1991. View Article : Google Scholar : PubMed/NCBI
27	Sakamoto M, Hirohashi S and Shimosato Y: Early stages of multistep hepatocarcinogenesis: Adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol. 22:172–178. 1991. View Article : Google Scholar : PubMed/NCBI