Combination of alpha-fetoprotein and neutrophil-to-lymphocyte ratio to predict treatment response and survival outcomes of patients with unresectable hepatocellular carcinoma treated with immune checkpoint inhibitors

Abstract

Background Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of hepatocellular carcinoma (HCC). However, long-term survival outcomes and treatment response of HCC patients undergoing immunotherapy is unpredictable. The study aimed to evaluate the role of alpha-fetoprotein (AFP) combined with neutrophil-to-lymphocyte ratio (NLR) to predict the prognosis and treatment response of HCC patients receiving ICIs. Methods Patients with unresectable HCC who received ICI treatment were included. The HCC immunotherapy score was developed from a retrospective cohort at the Eastern Hepatobiliary Surgery Hospital to form the training cohort. The clinical variables independently associated with overall survival (OS) were identified using univariate and multivariate Cox regression analysis. Based on multivariate analysis of OS, a predictive score based on AFP and NLR was constructed, and patients were stratified into three risk groups according to this score. The clinical utility of this score to predict progression-free survival (PFS) and differentiate objective response rate (ORR) and disease control rate (DCR) was also performed. This score was validated in an independent external validation cohort at the First Affiliated Hospital of Wenzhou Medical University. Results Baseline AFP ≤ 400 ng/ml (hazard ratio [HR] 0.48; 95% CI, 0.24–0.97; P = 0.039) and NLR ≤ 2.77 (HR 0.11; 95% CI, 0.03–0.37; P<0.001) were found to be independent risk factors of OS. The two labolatory values were used to develop the score to predict survival outcomes and treatment response in HCC patients receiving immunotherapy, which assigned 1 point for AFP > 400 ng/ml and 3 points for NLR > 2.77. Patients with 0 point were classified as the low-risk group. Patients with 1–3 points were categorized as the intermediate-risk group. Patients with 4 points were classified as the high-risk group. In the training cohort, the median OS of the low-risk group was not reached. The median OS of the intermediate-risk group and high-risk group were 29.0 (95% CI 20.8–37.3) months and 16.0 (95% CI 10.8–21.2) months, respectively (P < 0.001). The median PFS of the low-risk group was not reached. The median PFS of the intermediate-risk group and high-risk group were 14.6 (95% CI 11.3–17.8) months and 7.6 (95% CI 3.6–11.7) months, respectively (P < 0.001). The ORR and DCR were highest in the low-risk group, followed by the intermediate-risk group and the high-risk group (P < 0.001, P = 0.007, respectively). This score also had good predictive power using the validation cohort. Conclusion The HCC immunotherapy score based on AFP and NLR can predict survival outcomes and treatment response in patients receiving ICI treatments, suggesting that this score could serve as a useful tool for identification of HCC patients likely to benefit from immunotherapy.

Neutrophil-to-Lymphocyte Ratio and Early Tumor Shrinkage as Predictive Biomarkers in Unresectable Hepatocellular Carcinoma Patients Treated With Lenvatinib, PD-1 Inhibitors, in Combination With TACE

“…Nonetheless, nearly 40% of patients in this cohort did not receive an objective response, emphasizing the importance of identifying potential predictors for better clinical decisions. Many biomarkers dependent on molecules or genes have been found in HCC patients who were treated with systemic treatment, 9,12,[30][31][32][33][34] but each of them has not been described to be predictive markers of therapeutic response so far.…”

The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapies for the Treatment of Intermediate and Advanced Hepatocellular Carcinoma Unsuitable for Transarterial Chemoembolization

“… 33 In contrast, lymphocyte depletion has been associated with impaired antitumor immune responses. 34 NLR, which indicates the balance between the pro-tumor inflammatory state and the anti-tumor immune response, is increasingly being used to predict HCC survival. 35 High NLR (≥4) was associated with diminished survival and inadequate treatment response in HAIC-treated patients.…”

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges

“…The clinical utility of biomarkers is still under discussion, largely due to their low sensitivity and specificity to HCC. Additionally, authors differ significantly regarding the cut-off points for assessing tumor progression with these biomarkers [29][30][31][32][33][34][35][36].…”