Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation

Abstract

We evaluated the prognostic value of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC). Their association with programmed death ligand 1 (PD-L1) expression and vascular formation was further investigated. In this retrospective study, using a database of 418 patients who had undergone ¹⁸F-FDG PET/CT before hepatic resection for HCC, immunohistochemical staining of PD-L1, clusters of differentiation (CD) 8, CD68, and CD34 was performed. Patients with a high maximum standardized uptake value (SUVmax) on ¹⁸F-FDG PET/CT showed a significantly worse recurrence-free survival (RFS) (hazard ratio [HR]: 1.500; 95% confidence interval [CI]: 1.088-2.069; <i>P</i> = 0.0133) and overall survival (OS) (HR: 2.259; 95% CI: 1.276-4.000; <i>P</i> = 0.0052) than patients with a low SUVmax. Logistic regression analysis showed that a high SUVmax in HCC was significantly associated with PD-L1-positive expression (odds ratio: 4.407; 95% CI: 2.265-8.575; <i>P</i> < 0.0001). SUVmax values of HCC were associated with intratumoral CD8-positive T-cell counts (<i>P</i> = 0.0044) and CD68-positive macrophage counts (<i>P</i> = 0.0061). Stratification based on SUVmax, PD-L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. SUVmax, VETC, and PDL1 expression were independently predictive of survival on multivariable analysis. <i>Conclusion:</i> Our large cohort study showed that a high SUVmax on ¹⁸F-FDG PET/CT is associated with a poor clinical outcome and PD-L1 expression in patients with HCC. Additionally, stratification of patients based on the combination of SUVmax, PD-L1 expression, and the VETC status predicts poor clinical outcome.