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 SUV_max 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 SUV_max 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 SUV_max in the primary tumor were 2.63 for RFS and 2.66 for OS. A high uptake of ⁶⁸Ga-NOTA-AE105 (SUV_max 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 SUV_max 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 SUV_max, ¹⁸F-FDG SUV_max, TNM stage, and p16 status, only ⁶⁸Ga-uPAR SUV_max 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 SUV_max 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.

这项 II 期临床试验 (NCT02965001) 的目的是评估尿激酶型纤溶酶原激活物受体 (uPAR) PET/CT 与新型配体⁶⁸ Ga-NOTA-AE105 在头颈癌中的预后价值，并将其与¹⁸ F-FDG。方法：转诊接受根治性放疗的头颈部鳞状细胞癌患者符合条件并被前瞻性纳入本研究。⁶⁸ Ga-uPAR 和¹⁸ F-FDG PET/CT 在治疗性放疗开始前进行，SUV _max由 2 名独立读者在两项 PET/CT 研究中测量原发肿瘤的比例。计算无复发生存期 (RFS) 和总生存期 (OS)，并分别建立⁶⁸ Ga-uPAR 和¹⁸ F-FDG PET 的最佳截止值，并使用对数秩和 Kaplan-Meier 统计以及单变量和多变量进行比较Cox 比例风险模型中的分析。结果：共纳入 57 名患者，中位随访时间为 33.8 个月（范围 2.30-47.2 个月）。⁶⁸ Ga-uPAR 和¹⁸ F-FDG原发肿瘤的SUV_最大值中位数为 2.98（范围，1.94-5.24）和 15.7（范围，4.24-45.5）。⁶⁸ Ga-NOTA-AE105 SUV的最佳截止值_{RFS 在原发肿瘤中的最大值}为 2.63，OS 为 2.66。⁶⁸ Ga-NOTA-AE105的高摄取（SUV_最大值高于截止值）与较差的 RFS 和 OS 显着相关（对数秩P  = 0.012 和P  = 0.022）。⁶⁸ Ga-NOTA-AE105 在原发肿瘤中的摄取与单变量分析中较差的 RFS 显着相关（风险比 [HR]，8.53 [95% CI，1.12-64.7]；P  = 0.038），并且与 OS 相关（ HR，7.44 [95% CI，0.98–56.4]；P  = 0.052）。对于¹⁸ F-FDG PET，RFS 的最佳截止值为 22.7，OS 的最佳截止值为 22.9。最大¹⁸ F-FDG _SUV高于截止值与降低 RFS（对数秩P  = 0.012）和 OS（对数秩P  = 0.000）显着相关。¹⁸ F-FDG 摄取与 RFS（HR，3.27 [95% CI，1.237–8.66]；P  = 0.017）和 OS（HR，7.10 [95% CI，2.60–19.4]；P  < 0.001）显着相关单变量分析。在包括⁶⁸ Ga-uPAR SUV _max、¹⁸ F-FDG SUV _max、TNM 分期和 p16 状态的多变量分析中，只有⁶⁸ Ga-uPAR SUV _max仍然显着（HR，8.51 [95% CI，1.08-66.9]；P  = 0.042) 对于 RFS。对于 OS，只有 TNM 阶段和¹⁸F-FDG 仍然显着。结论：与 18 F-FDG PET、TNM 分期相比，目前的试验显示，与¹⁸ F-FDG PET、TNM 分期相比，在原发性肿瘤中使用⁶⁸ Ga-uPAR PET SUV _max来预测头颈部鳞状细胞癌患者接受根治性放疗时的 RFS有希望的结果, 和 p16 状态。⁶⁸ Ga-uPAR PET 可能对识别适合降级治疗和风险分层随访计划的患者具有潜在价值。