Zhou Xin, Yan Shi, Ma Xiaopan, Zhu Hua, Liu Bing, Yang Xin, Jia Bing, Yang Zhi, Wu Nan, Li Nan
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Nuclear Medicine, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd, Beijing, 100142, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing, 100142, China.
Eur J Nucl Med Mol Imaging. 2025 Feb 6. doi: 10.1007/s00259-025-07115-3.
This study aimed to assess the predictive and evaluative value of PD-L1 targeted Ga-THP-APN09 PET/CT in the neoadjuvant immunotherapy combined with chemotherapy for resectable non-small cell lung cancer (NSCLC), and to explore its potential in indicating immunotherapy-related adverse effects (irAEs).
Fifty patients with resectable NSCLC enrolled in this prospective study underwent baseline Ga-THP-APN09 PET/CT and F-FDG PET/CT, with follow-up F-FDG PET/CT conducted, additionally, 36 patients received follow-up Ga-THP-APN09 PET/CT. Surgery was performed following 2-4 cycles of toripalimab combined with chemotherapy if R0 resection was feasible. The major pathologic response (MPR) state of the post-operative specimen and the adverse effects following combined therapy were documented. The correlation between PD-L1 expression and baseline Ga-THP-APN09 PET/CT uptake was determined. The predictive and evaluative efficacies of baseline and follow-up Ga-THP-APN09 PET/CT, along with F-FDG PET/CT, in determining MPR, were compared.
The SUV values of baseline Ga-THP-APN09 PET/CT were significantly higher in patients exhibiting high-positive PD-L1 expression compared to those with low-positive and negative expression (P = 0.001). And the SUV values of baseline Ga-THP-APN09 PET/CT in the response group, as determined by F-FDG PET/CT evaluation, were significantly higher than those in the non-response group (3.4 vs. 2.4, P < 0.001). Totally, 41 patients underwent surgery, of which 27 achieved MPR, while 14 did not. The SUV in baseline Ga-THP-APN09 PET/CT demonstrated statistical significance between the MPR and non-MPR groups, with area under the ROC curve (AUC) of 0.88 (95%CI: 0.77-0.99) in identifying MPR. However, the SUV in baseline F-FDG PET/CT failed to demonstrated significant predictive power, with AUC values of 0.68 (95%CI: 0.50-0.86, P = 0.076). While the SUV in follow-up Ga-THP-APN09 and F-FDG PET/CT, along with their change rate (ΔSUV%), demonstrated good predictive efficacy in identifying MPR, with AUC values of 0.81 (0.64-0.98), 0.91 (0.82-1.00), 0.93 (0.84-1.00), and 0.96 (0.89-1.00), respectively. Furthermore, the follow-up Ga-THP-APN09 PET/CT could remarkedly indicate the potential for thyroiditis.
Baseline Ga-THP-APN09 PET/CT alone could predict efficacy and assist in patient screening for immunotherapy combined chemotherapy in resectable NSCLC, and the follow-up Ga-THP-APN09 PET/CT and their change rates could aid in therapy evaluation. Additionally, follow-up Ga-THP-APN09 PET/CT could be utilized to monitor the immunotherapy-related thyroiditis during the therapy.
NCT05156515, registered 8 December 2021, https://register.
gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw .
本研究旨在评估靶向程序性死亡配体1（PD-L1）的镓-四氢吡咯-APN09正电子发射断层扫描/计算机断层扫描（Ga-THP-APN09 PET/CT）在可切除非小细胞肺癌（NSCLC）新辅助免疫治疗联合化疗中的预测和评估价值，并探讨其在提示免疫治疗相关不良反应（irAEs）方面的潜力。
50例纳入本前瞻性研究的可切除NSCLC患者接受了基线Ga-THP-APN09 PET/CT和氟代脱氧葡萄糖（F-FDG）PET/CT检查，并进行了随访F-FDG PET/CT检查，另外，36例患者接受了随访Ga-THP-APN09 PET/CT检查。如果可行，在替雷利珠单抗联合化疗2-4个周期后进行手术。记录术后标本的主要病理反应（MPR）状态以及联合治疗后的不良反应。确定PD-L1表达与基线Ga-THP-APN09 PET/CT摄取之间的相关性。比较基线和随访Ga-THP-APN09 PET/CT以及F-FDG PET/CT在确定MPR方面的预测和评估效能。
与低阳性和阴性表达的患者相比，高阳性PD-L1表达患者的基线Ga-THP-APN09 PET/CT的标准化摄取值（SUV）显著更高（P = 0.001）。并且，根据F-FDG PET/CT评估确定的反应组中基线Ga-THP-APN09 PET/CT的SUV值显著高于无反应组（3.4对2.4，P < 0.001）。共有41例患者接受了手术，其中27例达到MPR，而14例未达到。基线Ga-THP-APN09 PET/CT中的SUV在MPR组和非MPR组之间具有统计学意义，在识别MPR方面的受试者工作特征曲线下面积（AUC）为0.88（95%置信区间：0.77-0.99）。然而，基线F-FDG PET/CT中的SUV未能显示出显著的预测能力，AUC值为0.68（95%置信区间：0.50-0.86，P = 0.076）。而随访Ga-THP-APN09和F-FDG PET/CT中的SUV及其变化率（ΔSUV%）在识别MPR方面显示出良好的预测效能，AUC值分别为0.81（0.64-0.98）、0.91（0.82-1.00）、0.93（0.84-1.00）和0.96（0.89-1.00）。此外，随访Ga-THP-APN09 PET/CT可显著提示甲状腺炎的可能性。
单独的基线Ga-THP-APN09 PET/CT可以预测疗效并有助于可切除NSCLC患者免疫治疗联合化疗的筛选，随访Ga-THP-APN09 PET/CT及其变化率有助于治疗评估。此外，随访Ga-THP-APN09 PET/CT可用于监测治疗期间的免疫治疗相关甲状腺炎。
NCT05156515，于2021年12月8日注册，https://register.
gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw 。
