ABSTRACT
BACKGROUND: A well-recognized class effect of immune checkpoint inhibitors (ICI) is immune-related adverse events (IrAEs) ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Deaths are reported in < 5% of patients treated with ICI. There are, however, no reliable markers to predict the onset and severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAEs (grade ≥ 2) in hepatocellular carcinoma (HCC) patients treated with ICI. AIM: To test the association between NLR and PLR at baseline with development of clinically significant IrAEs (grade ≥ 2) in HCC patients treated with ICI. METHODS: Data was extracted from an international database from a consortium of 11 tertiary-care referral centers. NLR = absolute neutrophil count/absolute lymphocyte count (ALC) and PLR = platelet count/ALC. Cutoff of 5 was used for NLR and 300 for PLR based on literature. We also tested the association between antibiotic and steroid exposure to IrAEs. RESULTS: Data was collected from 361 patients treated between 2016-2020 across the United States (67%), Asia (14%) and Europe (19%). Most patients received Nivolumab (n = 255, 71%). One hundred sixty-seven (46%) patients developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥ 2 in 87 (52%) patients. In a univariable regression model PLR > 300 was significantly associated with a lower incidence of grade ≥ 2 IrAEs (OR = 0.40; P = 0.044). Similarly, a trend was observed between NLR > 5 and lower incidence of grade ≥ 2 IrAEs (OR = 0.58; P = 0.097). Multivariate analyses confirmed PLR > 300 as an independent predictive marker of grade ≥ 2 IrAEs (OR = 0.26; P = 0.011), in addition to treatment with programmed cell death ligand 1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (OR = 2.57; P = 0.037) and PD-1/tyrosine kinase inhibitor (OR = 3.39; P = 0.01) combinations. Antibiotic use was not associated with IrAE incidence (OR = 1.02; P = 0.954). Patients treated with steroids had a > 2-fold higher incidence of grade ≥ 2 IrAEs (OR = 2.74; P < 0.001), although 74% were prescribed steroids for the treatment of IrAEs. CONCLUSION: Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs, lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI. This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.
ABSTRACT
BACKGROUND: The Child-Turcotte-Pugh score (CTP) is the most commonly used tool to assess hepatic reserve and predict survival in hepatocellular cancer (HCC). The CTP stratification accuracy has been questioned and attempts have been made to improve the objectivity of the system. Serum insulin-like growth factor-1 (IGF-1)-CTP has been proposed to improve CTP prognostic accuracy. We aimed to validate the IGF-CTP score in our patient population. PATIENTS AND METHODS: A total of 84 diagnosed HCC patients were enrolled prospectively. IGF-CTP scores in addition to CTP scores were calculated. C-index was used to compare the prognostic significance of the two scoring systems and overall survival (OS). RESULTS: Cirrhosis was present in 48 (57.1%) patients, 35 (41.7%) patients were non-cirrhotic, 36 (42.8%) patients were hepatitis B (HBV) positive, and 8 (9.5%) patients were hepatitis C (HCV) positive. Serum IGF-1 levels were significantly lower in cirrhotic compared with non-cirrhotic patients (p=0.04). There was a significant difference in OS rates of patients with serum IGF-1 level <50 ng/mL and patients with serum IGF-1 levels ≥50 ng/mL (p=0.02); the OS rates were 6.5 and 14.8 months, respectively (p=0.02). The median OS of all patients was 7.38 months (95% CI: 5.89-13.79). The estimated C-index for CTP and IGF-CTP scores was 0.605 (95% CI: 0.538, 0.672) and 0.599 (95% CI: 0.543, 0.655), respectively. The U statistics indicated that the C-indices between two scoring systems are not statistically different (P= 0.91). CONCLUSION: This study evaluated IGF-1 levels and the IGF-CTP classification in a predominantly HBV (+) cohort of HCC patients with 41.7% non-cirrhotic. Although the prognostic value was similar, among patients with CTP-A, class those reclassified as IGF-CTP B had shorter OS than those with IGF-CTP score A. Thus, further validations of IGF-CTP score in similar populations may add additional value as a stratification tool to predict HCC outcome.
