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Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database.

ABSTRACT: Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates ?-fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and underwent LT between 2012 and -2014. On explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post-LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score ?5 (P < .001). Post-LT HCC recurrence probability within 3 years increased from 1.6% with RETREAT score of 0% to 29% for a score ?5 (P < .001). Increasing RETREAT score was also associated with a shorter time to HCC recurrence. RETREAT was superior to Milan criteria (explant) in predicting HCC recurrence by the net reclassification index (P < .001). This study validates the prognostic power of RETREAT, which may help standardize post-LT surveillance, provide a framework for tumor staging and risk stratification, and select candidates for adjuvant therapies.

SUBMITTER: Mehta N

PROVIDER: S-EPMC6445634 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database.

Mehta Neil N Dodge Jennifer L JL Roberts John P JP Yao Francis Y FY

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20171202 5

Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates α-fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and und ...[more]

PMID: 29068145

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Project description:Background: There is not yet an effective marker in predicting the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC) patients. The Gustave Roussy Immune Score (GRIm-Score) based on three objective variables, namely, neutrophil-to-lymphocyte ratio (NLR), serum albumin level (ALB), and lactate dehydrogenase (LDH), was developed as feasible prognostic indication in lung cancer patients receiving ICIs therapies. Our study aimed to adapt the GRIm-Score (HCC-GRIm-Score) in HCC patients who received ICIs therapies and thus improving the predictive ability. Methods: From January 2018 to September 2020, 261 patients who received ICIs therapy were retrospectively included and divided into training and validation groups. After determining the factors for HCC-GRIm-Score by multivariable analysis from training group, the optimized HCC-GRIm-Score was validated and compared to the original GRIm-Score and the Barcelona clinic liver cancer (BCLC) staging system. Results: One hundred sixty-one and 80 patients were assigned into the training and validation groups, respectively. Two more factors, aspartate transaminase-to-alanine transaminase ratio [hazard ratio (HR), 1.51; 95% confidence interval (CI), 0.94-2.42] and total bilirubin (HR, 1.76; 95% CI, 1.07-2.88), were identified as independent prognostic factors for overall survival (OS) and integrated in the HCC-GRIm-Score system according to the multivariable analysis. A risk score based on the HCC-GRIm-Score indicated that patients presenting high score (>2) suffered from significantly shorter median OS of 10.3 months compared to those with a low score (not reached; HR, 2.99; 95% CI, 1.89-4.75; p < 0.001). In the validation group of 80 patients, the patients presenting a high score showed an inferior OS (HR 5.62, 95% CI, 1.25-25.24; p = 0.024). HCC-GRIm-Score had the highest area under curve of 0.719 (95% CI, 0.661-0.773) compared to original GRIm-Score and BCLC staging system. Conclusion: The present study confirmed that the modified HCC-GRIm-Score system provided superior predictive ability in identifying the HCC patients potentially benefit from ICIs therapies, compared to the original GRIm-Score and the BCLC staging system.

Project description:BackgroundTypically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications.Methods and findingsSystematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus.ConclusionsTwo independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary.

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Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database.

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Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database.

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