Prognostic Value of Urokinase-Type Plasminogen Activator Receptor PET/CT in Head and Neck Squamous Cell Carcinomas and Comparison with 18F-FDG PET/CT: A Single-Center Prospective Study.

The aim of this phase II clinical trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR) PET/CT with the novel ligand 68Ga-NOTA-AE105 in head and neck cancer and compare it with 18F-FDG. Methods: Patients with head and neck squamous cell carcinoma referred for curatively intended radiotherapy were eligible and prospectively included in this study. 68Ga-uPAR and 18F-FDG PET/CT were performed before initiation of curatively intended radiotherapy, and the SUVmax of the primary tumor was measured on both PET/CT studies by 2 independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated, and optimal cutoffs were established for 68Ga-uPAR and 18F-FDG PET independently and compared using log rank and Kaplan-Meier statistics, as well as univariate and multivariate analysis in a Cox proportional-hazards model. Results: In total, 57 patients were included and followed for a median of 33.8 mo (range, 2.30-47.2, mo). The median SUVmax of the primary tumors was 2.98 (range, 1.94-5.24) for 68Ga-uPAR and 15.7 (range, 4.24-45.5) for 18F-FDG. The optimal cutoffs for 68Ga-NOTA-AE105 SUVmax in the primary tumor were 2.63 for RFS and 2.66 for OS. A high uptake of 68Ga-NOTA-AE105 (SUVmax above cutoff) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). 68Ga-NOTA-AE105 uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (hazard ratio [HR], 8.53 [95% CI, 1.12-64.7]; P = 0.038), and borderline-associated with OS (HR, 7.44 [95% CI, 0.98-56.4]; P = 0.052). For 18F-FDG PET, the optimal cutoffs were 22.7 for RFS and 22.9 for OS. An 18F-FDG SUVmax above the cutoff was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). 18F-FDG uptake was significantly associated with reduced RFS (HR, 3.27 [95% CI, 1.237-8.66]; P = 0.017) and OS (HR, 7.10 [95% CI, 2.60-19.4]; P < 0.001) in univariate analysis. In a multivariate analysis including 68Ga-uPAR SUVmax, 18F-FDG SUVmax, TNM stage, and p16 status, only 68Ga-uPAR SUVmax remained significant (HR, 8.51 [95% CI, 1.08-66.9]; P = 0.042) for RFS. For OS, only TNM stage and 18F-FDG remained significant. Conclusion: The current trial showed promising results for the use of 68Ga-uPAR PET SUVmax in the primary tumor to predict RFS in head and neck squamous cell carcinoma patients referred for curatively intended radiotherapy when compared with 18F-FDG PET, TNM stage, and p16 status. 68Ga-uPAR PET could potentially become valuable for identification of patients suited for deescalation of treatment and risk-stratified follow-up schemes.

Hepatic erythropoietin response in cirrhosis.

BACKGROUND: Erythropoietin (EPO) is produced in the liver during fetal life, but after birth the production shifts to the kidneys. The liver maintains a production capacity of 10% of the total EPO-production, but can be up-regulated to 100%. Previous studies have demonstrated both elevated and reduced concentrations of EPO in cirrhosis. Increased EPO concentrations could be expected due to anemia, hypoxia, renal hypoperfusion, or EPO-mediated hepatoprotective mechanisms. In contrast, poor hepatic production capacity may cause reduced EPO concentrations in cirrhosis. In the present paper we aimed to study hepatic and renal venous concentrations of EPO in relation to the severity of the disease. MATERIALS AND METHODS: We included 24 patients with alcoholic cirrhosis and eight age-matched healthy controls. All had a full catheterization performed with the determination of EPO concentrations in the hepatic, renal and femoral veins and artery. All patients were clinically, biochemically, and hemodynamically characterized. RESULTS: The median arterial EPO concentrations in the cirrhotic patients and controls were 7.1 mIU/mL (range 3.5-179) and 7.2 mIU/mL (range 3.8-15.3), respectively. In the patient group we found no significant correlations to stage of disease of hemodynamic derangement. CONCLUSION: We found no significant differences in EPO concentrations across the liver, kidney, or peripheral circulation in the patient or control groups; and no significant correlations to clinical, biochemical, or hemodynamic characteristics. This suggests that hepatic EPO synthesis is not enhanced in cirrhosis, but larger scale studies are needed to clarify this question.