International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Degroote, Helena; Piñero, Federico; Costentin, Charlotte; Notarpaolo, Andrea; Boin, I.F.S.F.; Boudjéma, Karim; Baccaro, Cinzia; Chagas, Aline Lopes; Bachellier, Philippe; Ettorre, Giuseppe Maria; Poníachik, Jaime; Muscari, Fabrice; Benedetto, F. Di; Duque, Sergio Hoyos; Salamé, Ephrem; Cillo, U.; Gadano, Adrián; Vanlemmens, Claire; Fagiuoli, S.; Rubinstein, Fernando; Burra, Patrizia; Cherqui, Daniel; Silva, Marcelo; Vlierberghe, Hans Van; Duvoux, Christophe

doi:10.1016/j.jhepr.2021.100331

Cited by 11 publications

(9 citation statements)

References 31 publications

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“…[1][2][3] Even though a great progress has been made in the treatment of HCC including curative resection or liver transplantation, tumor-directed therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), radioembolization, as well as new systemic therapy beyond sorafenib, disease prognosis remains very poor. [4][5][6] Recent HCC surveillance data from the United States show improved 5-year overall survival following treatment in HCC diagnosed in its early stages (44% versus 11%). [7][8][9][10][11] Liver ultrasound (US) alone or combination with serum alpha-fetoprotein (AFP) every 6-months is the standard of care for HCC screening of patients with cirrhosis, although this approach lacks the sensitivity and specificity to reliably detect HCC at an early stage.…”

Section: Introductionmentioning

confidence: 99%

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis

Aydın¹,

Köksal²,

Thevenot³

et al. 2021

JHC

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Background and Aims: Hepatocellular carcinoma (HCC) developing in the context of preexisting cirrhosis is characterized by impaired autophagy that results in increased exosome release. This study was conducted to determine whether circulating exosomes expressing glypican 3 (GPC3) could be utilized as a biomarker for HCC detection and treatment response in patients with cirrhosis. Methods: Immunohistochemistry was performed to assess p62 and GPC3 expression in the lesion and adjacent tissue from cirrhosis with HCC. GPC3-enriched exosomes were captured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic specificity of serum exosome-derived GPC3 (eGPC3) was determined using samples obtained from malignancyfree controls, malignancy-free cirrhotics, cirrhotics with confirmed HCC, and patients with a non-HCC malignancy. The performance of eGPC3 was validated using serum samples of HCC patients received chemotherapy. Results: We found that the expression of p62 and GPC3 was significantly increased in HCC tissues compared to adjacent cirrhotic liver. Impaired autophagy and exosome shedding were confirmed in HCC cell lines. Mass spectroscopic analysis revealed that GPC3 was enriched in exosomes isolated from HCC cell lines. An affinity ELISA assay was developed that specifically captures GPC3 positive exosomes in the serum. Total exosome concentration and eGPC3 were significantly elevated in cirrhotic patients with HCC as compared to the reference control groups. Furthermore, decreases in post-treatment exosome concentration and eGPC3 levels were more closely correlated with response to locoregional chemotherapy compared to change in serum AFP in HCC patients awaiting liver transplantation. Conclusion:We developed an affinity exosome capture assay to detect GPC3 enriched exosomes. Our preliminary assessment shows that GPC3 positive exosomes can be used for HCC detection and prediction of treatment outcomes.

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Section: Introductionmentioning

confidence: 99%

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis

Aydın¹,

Köksal²,

Thevenot³

et al. 2021

JHC

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“…A retrospective multicenter study by Mehta et al, which followed 109 patients who were eventually transplanted after DS, found 1- and 5-year survival rates of 95% and 80%, respectively 17 . Degroote et al retrospectively investigated patients from 47 different centers who received bridging or DS LRT before liver transplant and showed that patients after DS had similar posttransplant outcomes compared to those within Milan criteria 5 . These findings were corroborated by a systematic review and meta-analysis by Tan et al, which demonstrated a high success rate of DS, with greater than 50% of patients eventually receiving transplants, and a 74% 5-year survival based on intention-to-treat analysis 18 …”

Section: Discussionmentioning

confidence: 99%

“…The response to DS therapy can also serve as a predictor for posttransplant prognosis. Patients within UCSF criteria at listing and successfully downstaged have similar posttransplant outcomes compared with those within Milan at listing 5 . National and international guidelines have now recommended locoregional therapy to downstage patients to be within the Milan criteria and allow more patients with HCC to be eligible for transplant listing 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness analysis of interventional liver-directed therapies for downstaging of HCC before liver transplant

Wu,

Kwong,

Heller

et al. 2023

Liver Transplantation

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Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are the 2 most used modalities for patients with HCC while awaiting liver transplant. The purpose of this study is to perform a cost-effectiveness analysis comparing TACE and TARE for downstaging (DS) patients with HCC. A cost-effectiveness analysis was performed comparing TACE and TARE in DS HCC over a 5-year time horizon from a payer’s perspective. The clinical course, including those who achieved successful DS leading to liver transplant and those who failed DS with possible disease progression, was obtained from the United Network for Organ Sharing. Costs and effectiveness were measured in US dollars and quality-adjusted life years (QALYs). Probabilistic and deterministic sensitivity analyses were performed. TARE achieved a higher effectiveness of 2.51 QALY (TACE: 2.29 QALY) at a higher cost of $172,162 (TACE: $159,706), with the incremental cost-effectiveness ratio of $55,964/QALY, making TARE the more cost-effective strategy. The difference in outcome was equivalent to 104 days (nearly 3.5 months) in compensated cirrhosis state. Probabilistic sensitivity analyses showed that TARE was more cost-effective in 91.69% of 10,000 Monte Carlo simulations. TARE was more effective if greater than 48.2% of patients who received TACE or TARE were successfully downstaged (base case: 74.6% from the pooled analysis of multiple published cohorts). TARE became more cost-effective when the cost of TACE exceeded $4,831 (base case: $12,722) or when the cost of TARE was lower than $43,542 (base case: $30,609). Subgroup analyses identified TARE to be the more cost-effective strategy if the TARE cohort required 1 fewer locoregional therapy than the TACE cohort. TARE is the more cost-effective DS strategy for patients with HCC exceeding Milan criteria compared to TACE.

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“…The UCSF criteria might be considered a reasonable upper limit for applying downstaging protocols on a solely morphometric basis. However, in the all-comers cohort, a proportion of patients can be cured by LT, although the likelihood is clearly lower ( 20 , 21 ). Considering this, it might be ‘too restrictive’ or more precisely ‘too unspecific’, if patient selection for downstaging is only based on tumor size and number.…”

Section: Still Not Outdated: Morphometric Parameters—should There Be ...mentioning

confidence: 94%

Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation—Adjusting the Odds?

Seehofer¹,

Petrowsky²,

Schneeberger³

et al. 2022

Transpl Int

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Background and Aims: Morphometric features such as the Milan criteria serve as standard criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Since it has been recognized that these criteria are too restrictive and do not adequately display the tumor biology, additional selection parameters are emerging.Methods: Concise review of the current literature on patient selection for downstaging and LT for HCC outside the Milan criteria.Results: The major task in patients outside the Milan criteria is the need for higher granularity with patient selection, since the benefit through LT is not uniform. The recent literature clearly shows that beneath tumor size and number, additional selection parameters are useful in the process of patient selection for and during downstaging. For initial patient selection, the alpha fetoprotein (AFP) level adds additional information to the size and number of HCC nodules concerning the chance of successful downstaging and LT. This effect is quantifiable using newer selection tools like the WE (West-Eastern) downstaging criteria or the Metroticket 2.0 criteria. Also an initial PET-scan and/or tumor biopsy can be helpful, especially in the high risk group of patients outside the University of California San Francisco (UCSF) criteria. After this entry selection, the clinical course during downstaging procedures concerning the tumor and the AFP response is of paramount importance and serves as an additional final selection tool.Conclusion: Selection criteria for liver transplantation in HCC patients are becoming more and more sophisticated, but are still imperfect. The implementation of molecular knowledge will hopefully support a more specific risk prediction for HCC patients in the future, but do not provide a profound basis for clinical decision-making at present.

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International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Cited by 11 publications

References 31 publications

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis

Cost-effectiveness analysis of interventional liver-directed therapies for downstaging of HCC before liver transplant

Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation—Adjusting the Odds?

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