Multidisciplinary Management of Hepatocellular Carcinoma

Guy, Jennifer; Kelley, Robin K.; Roberts, John P.; Kerlan, Robert K.; Yao, Francis Y.; Terrault, Norah A.

doi:10.1016/j.cgh.2011.11.008

Cited by 47 publications

(30 citation statements)

References 82 publications

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“…Accurate staging at diagnosis of HCC is of enormous importance since tumor stage dictates the type of standard of care patients will receive 26. Patients at the very early and early stages of the disease are eligible for curative therapies including radiofrequency ablation, liver resection, and liver transplantation, which offer a better chance at long-term survival (50% to 70% 5-year survival rate).…”

Section: Discussionmentioning

confidence: 99%

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CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody

Hernandez¹,

Sun²,

England³

et al. 2016

Theranostics

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Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of HCCs. YY146, an anti-CD146 monoclonal antibody, was employed as a targeting molecule to which we conjugated the zwitterionic near-infrared fluorescence (NIRF) dye ZW800-1 and the chelator deferoxamine (Df). This enabled labeling of Df-YY146-ZW800 with 89Zr and its subsequent detection using PET and NIRF imaging, all without compromising antibody binding properties. Two HCC cell lines expressing high (HepG2) and low (Huh7) levels of CD146 were employed to generate subcutaneous (s.c.) and orthotopic xenografts in athymic nude mice. Sequential PET and NIRF imaging performed after intravenous injection of 89Zr-Df-YY146-ZW800 into tumor-bearing mice unveiled prominent and persistent uptake of the tracer in HepG2 tumors that peaked at 31.65 ± 7.15 percentage of injected dose per gram (%ID/g; n=4) 72 h post-injection. Owing to such marked accumulation, tumor delineation was successful by both PET and NIRF, which facilitated the fluorescence image-guided resection of orthotopic HepG2 tumors, despite the relatively high liver background. CD146-negative Huh7 and CD146-blocked HepG2 tumors exhibited significantly lower 89Zr-Df-YY146-ZW800 accretion (6.1 ± 0.5 and 8.1 ± 1.0 %ID/g at 72 h p.i., respectively; n=4), demonstrating the CD146-specificity of the tracer in vivo. Ex vivo biodistribution and immunofluorescent staining corroborated the accuracy of the imaging data and correlated tracer uptake with in situ CD146 expression. Overall, 89Zr-Df-YY146-ZW800 showed excellent properties as a PET/NIRF imaging agent, including high in vivo affinity and specificity for CD146-expressing HCC. CD146-targeted molecular imaging using dual-labeled YY146 has great potential for early detection, prognostication, and image-guided surgical resection of liver malignancies.

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Section: Discussionmentioning

confidence: 99%

“…However, despite the success of curative therapies, up to 80% of the patients recur within the first five years following treatment 26. Hence, comprehensive tumor removal is vital to prolonged disease-free survival.…”

Section: Discussionmentioning

confidence: 99%

CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody

Hernandez¹,

Sun²,

England³

et al. 2016

Theranostics

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“…1, 2 Liver resection and transplantation for patients with HCC beyond Milan criteria remains controversial. Recent multi-institutional study from the HCC East-West study group which included data from 9 centers in Europe, Japan, Argentina, and United States, reported 57% 5-year overall survival (OS) and 27% 5-year disease-free survival (DFS) for selected patients beyond Milan criteria but without major vascular invasion treated with liver resection.…”

Section: Introductionmentioning

confidence: 99%

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

et al. 2016

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Objectives To assess survival after liver resection and transplantation in patients with HCC beyond Milan criteria. Summary Background Data The role of liver resection and transplantation remains controversial for patients with hepatocellular carcinoma (HCC) beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center Methods Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. Results Of 608 patients beyond Milan without vascular invasion, 480 (79%) underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (p<0.001). Resection patients had larger tumors (median 9 cm, IQR: 6.5-12.9 cm versus median 4.1, IQR: 3.4-5.3 cm, p<0.001); transplant patients were more likely to have multiple tumors (78% versus 28%, p<0.001). Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all p<0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared to propensity-matched liver resection patients (p≥0.176); DFS in this propensity matched cohort was greater after liver transplantation (p≤0.017). Conclusions Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

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“…Although carcinoma of the cervix is one of the most common malignancies among women, metastases to the liver are rare [40]. Metastatic disease or recurrent lesions that are not amenable to local excision or regional radiation have poor prognosis and are often treated with palliative chemotherapy [41,42].…”

Section: Secondary Liver Cancers Other Than From Colorectal Cancersmentioning

confidence: 99%

Yttrium-90 Microspheres: A Review of Its Emerging Clinical Indications

Khajornjiraphan¹,

Thu²,

Chow³

2014

Liver Cancer

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Background: Many patients with liver malignancies are not candidates for resection, and systemic therapies are often not effective. Radioembolization (RE) is an alternative treatment for this group of patients. The safety and efficacy of RE with yttrium 90 (Y90) in patients with hepatocellular carcinoma (HCC) or metastatic colon cancer to the liver have been proven in several studies. However, fewer studies have focussed on the safety and efficacy of RE with Y90 in other extrahepatic primary and secondary liver cancers. The effect on outcomes of concomitant use of Y90 with a systemic therapy is still currently under investigation. Summary: A review of the published data on the use of RE as stand-alone, concomitant or sequential with other treatment modalities in HCC and other primary and secondary liver cancer is reported here. Key message: RE for the treatment of HCC and other extrahepatic, primary and secondary liver cancer has reasonable efficacy and acceptable toxicities. Definitive studies to establish the role of RE in the treatment of such malignancies are warranted.

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Multidisciplinary Management of Hepatocellular Carcinoma

Cited by 47 publications

References 82 publications

CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody

CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

Yttrium-90 Microspheres: A Review of Its Emerging Clinical Indications

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