Association of Radiation and Neutrophil to Lymphocyte Ratio with Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombus

Abstract

Hepatocellular carcinoma (HCC) is increasing in incidence worldwide with up to 60% of patients found to have a portal vein tumor thrombus at diagnosis. Recent studies demonstrated that high neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival in patients with hepatocellular carcinoma. Whether NLR can predict survival after local therapy, such as radiation (RT), is currently unknown. We, therefore, reviewed the patient outcomes with special focus on the type of therapies received. This study is a retrospective review of HCC patients with portal vein thrombus from a single institution diagnosed between 2010 and 2022. Follow up time was defined as time from diagnosis to death or last follow up visit. Cox regression models were used to analyze overall survival (OS) rates. One-hundred and forty-five patients met inclusion criteria. Median follow-up time was 4 months [interquartile range (IQR): 1.7 - 13 months]. Median NLR at diagnosis was 3.5 (IQR: 2.2-4.9). Forty patients received RT as part of their therapy. Higher NLR was associated with shorter survival (HR 1.10, 95% CI 1.04 - 1.17, p = 0.002). Treatment with RT improved OS (HR 0.55, 95% CI 0.35 - 0.86, p = 0.009). After controlling for NLR at diagnosis, the addition of radiation still provides survival benefit (HR 0.55, 95% CI 0.35 - 0.86, p = 0.01). In patients who received immunotherapy as the first systemic agent, RT improved OS (HR 0.47, 95% CI 0.22 - 1.01, p = 0.05). This improvement held even when controlling for NLR. In patients who received tyrosine kinase inhibitor (TKI) as first systemic agent, RT did not improve OS. However, when controlling for NLR in patients receiving TKI, RT did improve OS (HR 0.45, 95% CI 0.2 - 1.0, p = 0.05). This retrospective, hypothesis-generating analysis suggests that NLR at diagnosis could predict OS benefit of RT addition in certain patients. These results could be due to the effect of radiation on the immune system; however, further studies are needed.