The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.

The aim of this phase II 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 to 18F-fluorodeoxyglucose (18F-FDG). Materials and methodsPatients with head and neck squamous cell carcinoma (HNSCC) referred to curatively intended radiotherapy were eligible and prospectively included in this phase II study. A 68Ga-uPAR-and 18F-FDG-PET/CT were performed before initiation of curatively intended radiotherapy and maximum standardized uptake values (SUVmax) of the primary tumor was measured on both PET/CTs by two independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated and optimal cut-off values were established for 68Ga-uPAR-and 18F-FDG-PET independently and compared using log rank and Kaplan-Meier statistics, and univariate and multivariate analysis in Cox proportional hazards model. ResultsA total of 57 patients were included and followed for a median of 33.8 months (range 2.30-47.2). The median SUVmax of the primary tumors were 2.98 (range 1.94-5.24) for 68Ga-uPAR and 15.7 (range 4.24-45.5) for 18F-FDG. The optimal cut-off points for 68Ga-NOTA-AE105 SUVmax in the primary tumor was 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 (HR=8.53 (95% confidence interval (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 cut-off points were 22.7 for RFS and 22.9 for OS. 18F-FDG SUVmax above cut-off 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 and OS in univariate analysis (HR=3.27; 95% CI 1.237-8.66), p=0.017) and (HR=7.10; 95% CI 2.60-19.4), p<0.001).In a multivariate analysis including 68Ga-uPAR SUVmax, 18F-FDG SUVmax, Tumor, Node and Metastasis (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. ConclusionThe current phase II clinical trial showed promising results for the use of 68Ga-uPAR-PET SUVmax in the primary tumor to predict RFS in HNSCC patients referred to curatively intended radiotherapy when compared to 18F-FDG-PET, TNM stage and p16 status. 68Ga-uPAR-PET could potentially become valuable for identification of patients suited for de-escalation of treatment and risk stratified follow-up schemes.

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.