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Prognostic value of Urokinase-type Plasminogen Activator Receptor (uPAR)-PET/CT in Head and Neck Squamous Cell Carcinomas and Comparison with 18F-FDG-PET/CT: A single-center prospective study.

Louise Madeleine RisoerMalene Martini ClausenZaza UjmajuridzeMohammed FarhadiKim Francis AndersenAnnika LoftAndreas Kjaer
Published in: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2021)
Purpose: 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 Methods: Patients 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. Results: A 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 cut-off) 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. Conclusion: The 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.
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