Atezolizumab plus Bevacizumab as a Bridge for Liver Transplant in Hepatocellular Carcinoma
Gabriela Azevedo SolinoRaphael Paiva Cock FerreiraLuiz Augusto Carneiro D‘AlbuquerqueAlberto Queiróz FariasLívia Zardo TrindadeVitor Fiorin de VasconcellosMariana Poltronieri Pacheco
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Abstract:
We report the case of a 68-year-old male with alcohol-related cirrhosis, diagnosed with hepatocellular carcinoma (HCC) not eligible for liver transplant. After immunotherapy with atezolizumab associated with bevacizumab, he underwent a successful living donor liver transplantation (LT), not showing disease evidence or graft injury, maintaining clinically and radiologically stable 14 months after surgery. This is a successful report of combined atezolizumab plus bevacizumab being used as a bridge to LT in a patient with HCC, showing an important finding in therapy in patients with unresectable tumors at diagnosis.Keywords:
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Several retrospective analyses have recently shown the advantage of liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) at early tumor stages. Preliminary results of a prospective series of OLT for unresectable small HCC arising in cirrhosis are reported. Eighteen out of 22 patients (82%) are alive without evidence of HCC recurrence after a median follow-up of 11 months.
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Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly in patients with multinodular and large tumors. However, factors predictive of outcome after LT in patients with small tumors remain ill defined. We investigated which factors were related to mortality or tumor recurrence among 47 liver transplant recipients with liver cirrhosis and HCC and compared them with 107 patients with liver cirrhosis without tumor who underwent LT in the same period. Patients with HCC were older (P < .001), more frequently had cirrhosis of a viral origin (P < .001), and had lower Child-Pugh scores (P < .001) than patients without tumor. Survival of patients with and without tumor was not significantly different (P = .20). Among patients with HCC, those with lower recurrence-free survival rates had liver cirrhosis of a viral origin, vascular invasion, bilobar disease, and tumor-node-metastasis (TNM) stage IV. At multivariate analysis, the only factor associated with mortality or recurrence was TNM stage IV (P = .02). Our results suggest that in patients with HCC and TNM stage IV, LT might be contraindicated.
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Until establishment of the Milan criteria in 1996, long-term survival in many hepatocellular carcinoma (HCC) patients receiving liver transplants was elusive, raising questions about practicality of transplantation in these patients (1).
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It is our great pleasure to introduce the Focused Issue entitled: “ Recent Innovations in the Management of Hepatocellular Cancer in the Setting of Liver Transplantation ”. Liver transplantation (LT) is the unique curative treatment for both Hepatocellular carcinoma (HCC) and liver cirrhosis.
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We read with great interest the recent meta-analysis written by Koh and colleagues entitled "Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients" (1), which was published in the latest issue of Hepatobiliary Surgery Nutrition.The authors have reached an important conclusion that liver resection (LR) was associated with poorer overall survival (OS) and disease-free survival (DFS) compared to liver transplantation (LT) and found similar results among intention-to-treat (ITT) studies.In uninodular hepatocellular carcinoma (HCC), DFS is poorer in LR, but OS was comparable to LT.In addition, subgroup analysis revealed that in Europe and North America, LR had poorer OS versus LT, but OS was comparable in Asia.Before 2010, LR had inferior survival versus LT, but not after 2010.Cohorts that undergoing usual surveillance had worse OS after LR, but cohorts underwent enhanced surveillance had comparable OS after LT and LR.These findings emphasize that LT remains the ideal treatment option for HCC by removing both the tumor and the surrounding diseased liver, thus addressing the field change effect and lowering the risk of recurrence.Nevertheless, although the authors discussed some limitations, some deficiencies related to this meta-analysis still existed that we would like to raise.Firstly, there are some flaws in the literature search.To begin with, only two electronic databases (MEDLINE and Embase) were systematically searched for eligible literature.Second, only studies published in English were eligible for inclusion, which could inevitably introduce some language bias.Thus, to make this meta-analysis invulnerable, the authors are suggested to choose more electronic databases like Scopus, Web of Science, and Cochrane Library to search for eligible studies without language restriction.Secondly, regarding inclusion criteria, the eligible patients were diagnosed with HCC within Milan criteria.Nevertheless, after a careful review, we noticed that the authors appeared to have made an apparent mistake in this meta-analysis.The reference 27 is not about LR versus LT for HCC within Milan criteria (2).Third, in consideration of the heterogeneity is significantly high in the results section.It is critical to perform meta-regression and subgroup analyses to explore potential sources of heterogeneity.The covariates such as country (China versus the United States), year of publication (before 2010 versus 2010-2021), and sample size (>50 versus <50) might be taken into account when meta-regression and subgroup analyses are carried out.What's more, results were stratified by date of study, unimodular HCC, region and income were performed by the investigators.However, these forest plots weren't presented.We suggest that the investigators to provide these forest plots in supplementary materials.Finally, there is an ambiguity in this meta-analysis.In the results section, the authors claimed that LR was associated with poor OS outcome in HCC within Milan criteria.However, we are wondering what does the OS mean, 1-year survival or 3-year survival?The same as DFS.
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