Usefulness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in advanced hepatocellular carcinomas (original) (raw)
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Risk factors and management of post-liver transplant recurrence of hepatocellular carcinoma
Hepatoma Research, 2021
Hepatocellular carcinoma (HCC) is one of the most common indications for liver transplantation (LT). With expanding criteria and increasing number of transplants, post-transplant recurrence of HCC remains an important cause for concern and portends a poor survival in these patients. Traditionally, HCC recurrence post-LT has been notoriously difficult to manage and their outcomes dismal. A better understanding of the tumour biology and its interplay with the immune system, combined with newer oncological interventions has allowed for improved survivals in these patients. A useful classification of HCC recurrence is where it is divided into oligo-recurrence and disseminated recurrence. This system helps strategize their multidisciplinary management algorithm and prognosticate outcomes. We provide an overview of the factors which may predict recurrence and summarise the current evidence on the management of post-LT HCC recurrence.
Hepatoma Research, 2020
Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (HCC) recurrence post living donor liver transplantation (LDLT). Methods: Of 2363 LDLT's performed between 2005 to mid 2018, 435 (18.4%) were for HCC within our expanded selection criteria (absence of extrahepatic disease and vascular invasion, irrespective of tumor size and number). Survival after recurrence, and prognostic factors for these patients were studied. Results: Of 435 LDLT patients, 51% had HCC beyond Milan and 43% beyond UCSF criteria at the time of LDLT. pre-LT AFP > 100 ng/mL and tumour FDG-18 PET avidity predicted overall survival (OS), whereas pre-LT AFP > 100 ng/mL, UCSF criteria, and FDG-18 PET avidity predicted recurrence-free survival. Hundred patients (23%) developed HCC recurrence at a median time of 16 months (range 2-108 months) post LDLT. Lungs (53%), liver (37%), and bone (21%) were the most common sites of recurrence. Ninety-five patients received tyrosine kinase inhibitors (TKI) after recurrence and 62 received mTOR inhibitors (protocol-based after LDLT, or post recurrence). Surgical resection of metastases was performed in 14 patients, 15 received stereotactic body radiotherapy, and 18 underwent ablation (radiofrequency, microwave ablation, transarterial chemoembolisation, or percutaneous ethanol injection). One-and 3-yr OS after recurrence were 57%, and 24% respectively, with a maximum post recurrence survival of 7.5 years. HCC recurrence within one year after LDLT (P = 0.004, HR = 2.38, 95%CI: 1.325-4.276), AFP > 200 ng/mL at the time of recurrence (P =0.02, HR = 2.075, 95%CI: 1.121-3.841), and recurrence at multiple sites (P = 0.047, HR = 1.831, 95%CI: 1.009-3.321) were poor prognostics factors for post recurrence survival. Multimodality management of recurrence using combined medical, surgical, ablative treatments and radiotherapy significantly improved survival compared to the use of TKI’s or mTORi’s alone, or in combination. Conclusion: In patients accepted for LDLT beyond the conventional size-number criteria, even after HCC recurrence, an aggressive approach using multimodality therapy, when possible, aids in further prolongation of survival.
Outcomes of Patients With Hepatocellular Carcinoma After Liver Transplant
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2015
Liver transplant is one of the few effective treatments for hepatocellular carcinoma. Our aim in this study was to evaluate the risk factors for hepatocellular carcinoma recurrence after liver transplant. In this retrospective study, conducted between October 1988 and March 2015, four hundred seventy-three liver transplants were performed at our institution. Of these, 231 were pediatric and 242 were adult. Among these patients, liver transplant was performed in 58 patients (12.3%) for treatment of hepatocellular carcinoma. Hepatocellular carcinoma recurrence was detected in 14 patients (24.1%). Overall 5-year and 10-year survival rates of patients underwent liver transplant beyond the Milan criteria for hepatocellular carcinoma were 50.3% and 43.1%. Overall, 5- and 10-year survival rates of patients underwent liver transplant within the Milan criteria for hepatocellular carcinoma were 78.4% and 72.6%. The main predictive variable was whether the tumor had expensed beyond the Milan c...
Advances in Therapy, 2021
Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant (LT) is challenging. Most clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. We aimed to assess the outcomes in using various systemic therapies in patients with post-LT recurrence. Consecutive patients with HCC and recurrences following LT at a large tertiary centre from 2005 to 2018 were reviewed. Overall survival (OS), response rates and adverse events (AEs) were analysed. Forty-three consecutive patients with a recurrence of HCC following LT were identified from 2005 to 2018. Median OS from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months (CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p < 0.001) with a hazard ratio of 0.104 (log-rank test, p < 0....
Factors predicting survival after post-transplant hepatocellular carcinoma recurrence
Journal of hepato-biliary-pancreatic sciences, 2013
Although factors associated with an increased risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been extensively studied, the history of patients with a post-transplant recurrence is poorly known. Patients experiencing a post-transplant HCC recurrence from 1996 to 2011 in two transplant programs were included. Demographic, transplant, and post-recurrence variables were assessed. Thirty patients experienced an HCC recurrence-22 men and 8 women with a mean age of 55 ± 6 years. Sixteen (53 %) were outside the Milan criteria at the time of transplantation. Most recurrences (60 %) appeared within the first 18 months after transplantation, ranging between 1.7 and 109 months (median 14.2 months). Mean post-recurrence survival was 33 ± 31 months. On univariate analysis, total tumor volume (TTV; p = 0.047), microvascular invasion (p = 0.011), and time from transplant to recurrence (p = 0.001) predicted post-recurrence survival. On multivariate analysis, b...
Hepato-gastroenterology, 2013
The Up7 criteria for HCC have recently emerged to identify potential candidates for OLT. The aim of this study was to assess the validity of the Up7 criteria according to the pathological analysis of the explanted livers. For recurrence risk calculation 669 HCC transplanted patients were classified according to both the pathological Milan and Up7 criteria. In order to identify potential predictors of recurrence, selected biological tumor markers and morphological features were then tested by Cox regression. The 5-year HCC recurrence rate for the Milan out/Up7 in subgroup (n=87), was significantly higher than patients meeting Milan criteria (n=299), 15.8% vs. 9.4% (p=0.0290). For patients within the Up7 criteria (n=383), only pre-OLT AFP level >1000ng/mL and microvascular invasion were significant predictors for recurrence, and for those beyond the Up7 criteria (n=286), pre-OLT AFP level >1000ng/mL, poor differentiation grade and microvascular invasion remained significant. Com...
Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story
Annals of surgery, 2016
We sought to develop a "Model Of Recurrence After Liver transplant" (MORAL) for hepatocellular carcinoma (HCC). The Milan criteria are used to allocate livers to patients with HCC requiring liver transplantation (LT) but do not include objective measures of tumor biology. Biological markers including the neutrophil-lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) have been associated with recurrence risk. Prospective cohort study of adults undergoing LT for HCC between January 2001 and December 2012. A total of 339 patients were included. On multivariable Cox regression analysis, 3 preoperatively available factors were independent predictors of worse recurrence-free survival (RFS), namely, an NLR ≥ 5 (P < 0.0001, hazard ratio, HR: 6.2), AFP > 200 (P < 0.0001, HR: 3.8), and Size >3 cm (P < 0.001, HR: 3.2). The Pre-MORAL score was constructed from the hazard ratios and assigning patients points in an additive fashion, with a minimum of 0 points (no factors) ...