Transarterial Chemoembolization for Unresectable Hepatocelluar Carcinoma

Abstract: Transarterial chemoembolization has been shown to effectively downsize unresectable hepatocellular carcinoma, thereby “bridging” patients to liver transplant. We present a case of a 66-year-old male with cirrhosis and two unresectable liver lesions falling outside the Milan criteria. The patient was subsequently treated with transarterial chemoembolization, which downsized both lesions. Chemoembolization was well tolerated and the patient was successfully bridged to liver transplant, emphasizing the role of chemoembolization. 

Key words: chemoembolization, hepatocellular carcinoma, Milan criteria

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A 66-year-old male presented who had a history of liver cirrhosis secondary to genotype 2B Hepatitis C virus infection since 2007, status post interferon therapy with poor response. Follow-up cross-sectional imaging revealed two contiguous enhancing liver lesions measuring 4 cm and 1.8 cm located in segments III and II respectively without evidence of vascular invasion or portal venous thrombosis (Figures 1-3). Subsequent biopsy confirmed hepatocellular carcinoma (HCC) in July 2012. According to the Milan criteria, given the number and size of the lesions, the patient was deemed ineligible for liver transplant. As one of the two lesions is greater than 3 cm in diameter, the patient does not fall within the Milan criteria, which include the following:

• One lesion smaller than 5 cm or up to 3 lesions smaller than 3 cm
• No extrahepatic manifestations
• No vascular invasion

The patient’s clinical course was significant for fatigue, esophageal varices, and portal hypertensive gastropathy without complications of ascites or hepatic encephalopathy. Pertinent laboratory findings included bilirubin 1.6 mg/dL, creatinine 0.6 mg/dL, INR 1.2, albumin 3.3 mg/dL, and α-fetoprotein 142 with a MELD score of 11.

Treatment

Using a multidisciplinary approach, the patient was evaluated for bridge-to-transplant treatments to downsize the tumor burden to within the transplantable size criteria. Uneventful transarterial chemoembolization (TACE) using drug-eluting LC Beads (BTG) with doxorubicin to the largest liver lesion was performed in November 2012 with significant downsizing of tumor as evidenced by our routine 6-week follow-up triple-phase computed tomography (CT) study (Figures 4-6). At our institution a routine 4-week to 6-week follow-up CT scan is performed after TACE to determine the need for additional intervention while also allowing for proper patient clinical reassessment. Because the first treatment was well tolerated and there was persistent enhancement of the segment II lesion and residual marginal enhancement of the dominant segment III lesion, a second TACE was recommended and performed in January 2013 to achieve further tumor burden downsizing. A follow-up CT scan performed in February 2013 showed hypodense lesions without any contrast enhancement.

The patient was evaluated in the transplant clinic and underwent a successful liver transplantation in July 2013. The native liver post-explant analysis revealed a 90% necrosis in both segment II and III contiguous lesions, which measured together up to 3.7cm. Findings were consistent with total-subtotal tumor necrosis and successful chemoembolization response. 

Discussion

The Milan criteria is a proven, reliable guideline for liver transplantation selection of patients with unresectable HCC with 1 nodule smaller than 5 cm or no more than 3 nodules smaller than 3 cm. Patients who meet the criteria have a 5-year survival rate of more than 70% after transplantation.¹ However, rigorous application of said criteria excludes patients with slightly more advanced disease that could potentially benefit from liver transplantation with a favorable post-transplant survival rate. In order to have these patients listed for transplant, extension of the selection criteria has been proposed by different centers as well as HCC downsizing to within the Milan criteria.² University of California San Francisco criteria has modestly extended the transplant criteria to one lesions measuring no more than 6.5 cm or 2 to 3 lesions not exceeding 4.5 cm.³ Several bridge-to-transplant treatment modalities, such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), play a central role in HCC downsizing. TACE is considered to be the modality of choice for lesions >3 cm and focal disease that allows for selective embolization, whereas RFA could be the treatment of choice for lesions up to 3 cm.⁴ Other tools such as radioembolization with Yttrium-90 microspheres require further studies to confirm their role and efficacy.

Multiple retrospective studies have confirmed the usefulness of TACE as a bridge to liver transplantation with associated good survival rate, low rate of cancer recurrence, and good tolerability.⁵ Given these promising results and increased experience with TACE, a more thorough evaluation of patients presenting with individual high-risk factors for TACE-associated adverse effects (bilirubin ≥2mg/DL, albumin ≤3.5mg/dL, CP score of at least 9, multifocal disease, portal diversion, and occlusion or biliary obstruction) must ensue before treatment is denied as they are not at significant higher periprocedural morbidity and mortality.⁶ 

A multiphased CT scan should be performed at 4 to 6 weeks after treatment to evaluate the tumor response using the modified RECIST guidelines. Patients with complete response documented by CT scan have a better prognosis following transplantation and correlate with pathologic data of complete necrosis and lack of microvascular invasion, regardless of tumor size.⁷ Millonig et al determined that the 5-year survival rate was higher in patients with a complete tumor necrosis compared to those with partial necrosis (86% vs 66%).⁸ Furthermore, patients within the Milan criteria who did not respond to TACE and underwent liver transplantation demonstrated tumor recurrence. Hence, imaging assessment of tumor response serves as a valuable tool to further optimize patient selection for transplant.

A study performed by Yao et al selected 61 patients for downstaging of HCC using a multimodal approach of which 43 (70.5%) were successfully downsized to T2. After a close 3-month observation and confirmation of stable disease, 35 patients were transplanted with a 4-year survival rate of 92%.⁹ De Luna et al selected 27 patients outside of the Milan criteria for downstaging using TACE. Seventeen patients were downsized to T2 of which 15 underwent liver transplantation with a 3-year survival rate of 79% and tumor recurrence rate of 7%.¹⁰ 

Conclusion

Transarterial chemoembolization in patients with unresectable hepatocelluar carcinoma beyond the Milan criteria serves as an effective modality to safely downsize and bridge well selected patients to transplant, as demonstrated in this particular case. 

References

1. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693-699.
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8. Millonig G, Graziadei IW, Freund MC, et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2007;13(2):272-279.
9. Yao FY, Kerlan RK Jr, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: An intention-to-treat analysis.” Hepatology. 2008;48(3):819-827.
10. De Luna W, Sze DY, Ahmed A, et al. Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation. Am J Transplant. 2009;9(5):1158-1168.

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Editor’s note: This article underwent peer review by one or more members of the Interventional Oncology 360 editorial board.

Address for correspondence: Jason Salsamendi, MD, 1611 NW 12th Ave. West Wing 279, Miami, Florida 33136. Email: jsalsamendi@med.miami.edu

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no disclosures related to the content of this manuscript. 

Suggested citation: Arias CER, Salsamendi J. Transarterial chemoembolization for unresectable hepatocelluar carcinoma. Intervent Oncol 360. 2014;2(1):E1-E5.