The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study

Sapisochín, Gonzalo; Goldaracena, Nicolás; Laurence, Jerome M.; Dib, Martin J.; Barbas, Andrew S.; Ghanekar, Anand; Cleary, Sean P.; Lilly, Les; Cattral, Mark S.; Marquez, Max; Selzner, Markus; Renner, Eberhard L.; Selzner, Nazia; McGilvray, Ian; Greig, Paul D.; Grant, David

doi:10.1002/hep.28643

Cited by 269 publications

(219 citation statements)

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“…The patient survival of this series is lower than those within Milan criteria [12], but much better than the reported outcomes with palliative treatment, whether taken from the time of transplantation (71% at 3 years, 66% at 5 years) or from the time of listing (56% at 3 years, 47% at 5 years). For selected patients with non-transplantable HCC (i.e.…”

Section: Discussioncontrasting

confidence: 58%

“…Patients with any number and any size of HCC lesions are eligible for LT no evidence exists for vascular invasion or extrahepatic disease, no cancer-related constitutional symptoms are observed, and a targeted biopsy of the largest lesion does not show poor differentiation. Findings show that the LT outcomes for those beyond Milan but within the ETC were inferior compared to those within Milan, but were still acceptable [12]. However, no studies have specifically focused on the outcomes of patients with advanced HCC from the time of listing as reported herein.…”

Section: Introductionmentioning

confidence: 79%

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Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

et al. 2017

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Background:Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). Materials & Methods: All patients listed in the Toronto liver transplant program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiological images were reviewed by two independent radiologists. The primary endpoint was patient survival. Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p=0.02) and tumor burden (p <0.001). The majority of those listed underwent LT (n=69, 72%). Both tumor progression on waiting list .464], p=0.006) and peak AFP ≥400ng/ml ], p=0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% (n=24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p=0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93%, 71%, and 66%. Conclusion: LT provides significantly better survival rates than palliation for patients with selected advanced HCC. SYNOPSISIn most Western centers, palliation remains the only option for patients with advanced HCC with a 3-year survival <30%. This study reports an improved survival with liver transplantation (71%, 66% at 3, 5 years) of selected patients with advanced HCC.

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 79%

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

et al. 2017

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“…DuBay et al [46] included percutaneous biopsy in their criteria (Toronto), which did not impose any limitation to tumor number or size, in order to avoid OLT in patients with poorly differentiated HCC. Although, as previously discussed, these were further validated (extended Toronto criteria) by Sapisochin et al 47 , the vast heterogeneity of HCC, the low sensitivity of biopsy and the potential for bleeding or even needle track seeding, render routine biopsy not an easily recommended action 79 . Additionally, patients with decompensated cirrhosis may not be able to undergo biopsy owing to retention of ascites.…”

Section: Tumor Biology: Anaspect To Be Included In the Criteriamentioning

confidence: 98%

“…After reporting the results of a first retrospective cohort study [46], a research group went on with a second validation prospective cohort study 47 in an effort to prove that tumor size and number are not the only aspects that should be considered in patient selection for OLT, but tumor differentiation and tumor-related symptoms should be taken into consideration as well. These are named the extended Toronto criteria (after the validation study) and consist of no vascular invasion, no extrahepatic metastasis, no cancer-related symptoms, a percutaneous biopsy result of the largest tumor showing that it is not poorly differentiated and, most significantly, no tumor size or number limitation.…”

Section: Extended Toronto Criteriamentioning

confidence: 99%

The Evolution of Criteria for Liver Transplantation for Hepatocellular Carcinoma: From Milan to San Francisco and All Around the World!

Ziogas¹,

Tsoulfas²

2017

RFMH

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Introduction: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cancerrelated cause of death in the world. According to the stage of the disease, each patient is allocated to a different treatment option. Liver transplantation, along with surgical resection, is the only totally therapeutic option and is primarily indicated in HCC patients with underlying cirrhosis. However, the restricted number of liver grafts imposes difficulties in selecting the most suitable patients to receive those limited grafts and therefore certain criteria have been proposed. The Milan criteria are currently the most widely accepted and utilized criteria around the world, despite their restrictiveness. In an attempt to assist HCC patients exceeding them, but with a potential to display acceptable survival outcomes, undergo liver transplantation, research teams worldwide suggest expanded criteria based on their findings. Some of the most broadly known are the University of California, San Francisco (UCSF), Kyoto, Tokyo, Hangzhou and up-to-7 criteria. On the other hand, in order to expand the liver donor pool, grafts may be accepted from living, non-heart beating, elderly, steatotic, or even HCV-infected donors, in addition to the use of split livers with both advantages and disadvantages. The aim of this review is to thoroughly present the current situation of liver transplantation for HCC patients, with a focus on the criteria used and emerging challenges presented. Core tip: Hepatocellular carcinoma (HCC) is the third most common malignancy worldwide and liver transplantation represents the treatment of choice, particularly in the setting of cirrhosis. Lack of grafts led to the utilization of certain criteria in order to determine the eligibility of an HCC patient to access the waiting list. The most widely accepted are the Milan criteria, even though they are thought off as too restrictive. Consequently, transplant research groups all over the world published their own criteria, which showed acceptable outcomes. Living donor liver transplantation and other extended-criteria grafts have been proposed as an alternative to reduced donations. Ziogas IA, Tsoulfas G. The evolution of criteria for liver transplantation for hepatocellular carcinoma: from Milan to San Francisco and all around the world!

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“…6 A follow-up study by the same group demonstrated that 5-year survival rates for patients outside of the Milan criteria but within the UCSF criteria and the ETC were numerically lower but not significantly inferior than patients within the Milan criteria (68 vs. 76%; p = 0.07). 7 Aravinthan et al, the authors of the original ETC studies, examined their single institution, retrospective experience for OLT among 96 patients with HCC outside the UCSF criteria but within the ETC over a 15-year period. 8 The hypothesis of the authors is that better long-term survival could be achieved with OLT than locoregional or systemic therapy options, where historical 3-year survival rates are approximately 30% and 5-year survival rates are typically less than 5%.…”

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confidence: 99%

Expansion of Criteria for Liver Transplantation in Hepatocellular Carcinoma: Better Patient Selection or a Slippery Slope?

2017

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TXHepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and one of the leading causes of death in patients with cirrhosis.1 In appropriately selected patients, orthotopic liver transplantation (OLT) provides 5-year overall survival rates approaching 70% and is the only therapy that offers both a cure for the cancer and the underlying liver cirrhosis. Prior to publication of the Milan criteria by Mazzaferro et al. in 1996, early results of OLT for HCC were dismal due to the high rate of recurrence and poor overall outcome. Adherence to the Milan criteria, a solitary tumor B5 cm or with three or less tumors each B3 cm with no evidence of vascular invasion or extrahepatic metastasis, has led to excellent post-transplant survival and forms the framework to award priority for deceased donor allocation in the US utilizing the model for end-stage liver disease (MELD) score. 2Although adaptation of the Milan criteria has facilitated survival rates that approach those of non-HCC patients, some believe strict adherence to these criteria may preclude the benefits of OLT from patients with larger tumors. This has led to the development of several proposals for expanded transplant criteria, including the University of California San Francisco (UCSF) and up-to-seven criteria, whereupon selected patients beyond the Milan criteria could still be eligible for transplantation.3,4 Although initially designed based on retrospective pathological explant data, the UCSF criteria, but not the up-to-seven criteria, have been validated in studies using a priori pre-transplant radiographic imaging, with 5-year post-transplantation survival rates approaching 70%.5 Recently, expanded criteria adding surrogates of tumor biology to tumor size and number was proposed by the University of Toronto group. The extended Toronto criteria (ETC) allows OLT for HCC provided there is no evidence of cancer-related symptoms, extrahepatic spread, vascular invasion, or poor differentiation on pre-transplant biopsy. Patients who exceeded the Milan criteria but satisfied the ETC achieved 5-year survival rates of 70% in the original single-institution experience, although these results have not yet been externally validated.6 A follow-up study by the same group demonstrated that 5-year survival rates for patients outside of the Milan criteria but within the UCSF criteria and the ETC were numerically lower but not significantly inferior than patients within the Milan criteria (68 vs. 76%; p = 0.07). 7Aravinthan et al., the authors of the original ETC studies, examined their single institution, retrospective experience for OLT among 96 patients with HCC outside the UCSF criteria but within the ETC over a 15-year period. 8 The hypothesis of the authors is that better long-term survival could be achieved with OLT than locoregional or systemic therapy options, where historical 3-year survival rates are approximately 30% and 5-year survival rates are typically less than 5%.9,10 The authors found OLT afforded these patients 5-ye...

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The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study

Cited by 269 publications

References 34 publications

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

The Evolution of Criteria for Liver Transplantation for Hepatocellular Carcinoma: From Milan to San Francisco and All Around the World!

Expansion of Criteria for Liver Transplantation in Hepatocellular Carcinoma: Better Patient Selection or a Slippery Slope?

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