Dataset Information

Blood Biomarkers Predict Survival Outcomes in Patients with Hepatitis B Virus-Induced Hepatocellular Carcinoma Treated with PD-1 Inhibitors.

ABSTRACT:

Purpose

To investigate the prognostic value of blood markers in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) treated with PD-1 inhibitors. Patients and Methods. We retrospectively collected and analyzed the clinicopathological data of 110 HBV-induced HCC patients treated with PD-1 inhibitors. Progression-free survival (PFS) and overall survival (OS) were scrutinized using Kaplan-Meier analysis and the log-rank test, and all potential risk factors were analyzed with univariate and multivariate Cox regression analyses.

Results

The mean OS and PFS were 6.5 and 5.5 months, respectively. According to Kaplan-Meier survival curves, elevated systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) correlated with decreased OS and PFS (all P < 0.05), and low lymphocyte-to-monocyte ratio (LMR) correlated with decreased PFS and OS (all P < 0.05). Per multivariate Cox regression analyses, SII, PLR, and portal vein tumor thrombus (PVTT) correlated independently with PFS (all P < 0.05), whereas SII, PLR, NLR, and portal vein tumor thrombus (PVTT) correlated with OS (all P < 0.05).

Conclusion

SII, PLR, and PVTT predicted OS and PFS in HCC patients who received PD-1 inhibitors and, therefore, could be useful predictors for risk stratification and individualized therapeutic decision-making for patients with HBV-induced HCC treated with PD-1 inhibitors.

SUBMITTER: Huang R

PROVIDER: S-EPMC9402369 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Blood Biomarkers Predict Survival Outcomes in Patients with Hepatitis B Virus-Induced Hepatocellular Carcinoma Treated with PD-1 Inhibitors.

Huang Rui R Zheng Yanfen Y Zou Wenxue W Liu Chao C Liu Jibing J Yue Jinbo J

Journal of immunology research 20220817

<h4>Purpose</h4>To investigate the prognostic value of blood markers in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) treated with PD-1 inhibitors. <i>Patients and Methods</i>. We retrospectively collected and analyzed the clinicopathological data of 110 HBV-induced HCC patients treated with PD-1 inhibitors. Progression-free survival (PFS) and overall survival (OS) were scrutinized using Kaplan-Meier analysis and the log-rank test, and all potential risk factors we ...[more]

PMID: 36033384

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Project description:BackgroundAlthough peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear.MethodsWe prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features.ResultsWe found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05).ConclusionCirculating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Project description:IntroductionAlthough immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC.MethodsPatients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram.ResultsUnivariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells.Discussion/conclusionThe combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI.

Project description:Purpose: The purpose of this prospective observational study was to investigate the relationship between pretreatment neutrophil-to-lymphocyte ratio (NLR) and posttreatment early tumor shrinkage (ETS), and clinical outcomes in patients with unresectable hepatocellular carcinoma (uHCC) who received lenvatinib, programmed death-1 inhibitors plus transcatheter arterial chemoembolization. Patients and Methods: A total of 63 uHCC patients were treated with this triple combination. Multivariate analyses to determine the independent factors associated with overall survival (OS) were employed. The link between NLR and clinical results was further analyzed. Furthermore, the predictive value of combining NLR with ETS should be investigated to stratify patients receiving treatment for survival benefits. Results: Progression-free survival and OS were 9.8 and 23.0 months, respectively, with a median follow-up of 20.8 months. On a multivariate analysis of OS, NLR was the only independent prognostic factor. Patients with NLR low (NLR < 3.2) had longer progression-free survival (19.3 vs 7.3 months, P < 0.001) and OS (28.9 vs 16.9 months, P < 0.001), higher objective response rate (86.7% vs 39.4%, P < 0.001), and a higher chance of achieving ETS ≥ 10% (ETS high) (73.3% vs 21.1%, P < 0.001) compared with patients with NLR high (NLR ≥ 3.2). The Spearman correlation analysis also showed the strong consistency between NLR and ETS (R2 = 0.6751). In the subgroup analysis, greater OS benefit was found in the NLR low/ETS high group than the NLR high/ETS low group (χ2 = 31.258, P < 0.001), while there was no survival difference for patients in the NLR low/ETS low group compared with in the NLR high/ETS high group (χ2 = 0.046, P = 0.830). Conclusion: NLR has the potential to identify which patients would benefit from this triple therapy, and when combined with ETS, it has the potential to provide greater predictive power in selecting the appropriate candidates for this combination treatment.

Dataset Information

Blood Biomarkers Predict Survival Outcomes in Patients with Hepatitis B Virus-Induced Hepatocellular Carcinoma Treated with PD-1 Inhibitors.

Purpose

Results

Conclusion

Publications

Blood Biomarkers Predict Survival Outcomes in Patients with Hepatitis B Virus-Induced Hepatocellular Carcinoma Treated with PD-1 Inhibitors.

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