Yang Runjun, Tang Han, Xie Yunze, Cai Danjie, He Yibo, Zheng Zhe, Lin Yu, Gao Huaping, Tang Wenxin, Yan Yihan, Tan Lijie, Shi Hongcheng
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 in Fenglin Road, Shanghai, 200032, P.R. China.
Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
Eur J Nucl Med Mol Imaging. 2025 Mar;52(4):1422-1435. doi: 10.1007/s00259-024-07051-8. Epub 2025 Jan 2.
To investigate the predictive value of 2-[18F]-fluoro-2-deoxy-D-glucose ([F]FDG) PET/CT for evaluating primary tumor (PT) and lymph node (LN) responses after neoadjuvant programmed death-ligand 1 (PD-L1) blockade monotherapy in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).
In the single-arm phase 1b NATION-1907 trial (NCT04215471), 23 patients with LA-ESCC received two cycles of neoadjuvant PD-L1 blockade Adebrelimab followed by surgery. Among these, 18 patients underwent [F]FDG PET/CT scans both before immunotherapy and prior to surgery. Standardized uptake value corrected for lean body mass (SUL)-derived parameters, including SUL and SUL, were documented for PTs and LNs. Lesions > 1cm were segmented using thresholds of 41% and 50% of SUL, respectively, following European Association of Nuclear Medicine (EANM) guidelines, with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated. Percentage changes of all metabolic parameters were also recorded. Residual viable tumor ≤ 33% were classified as well-responders, whereas residual viable tumor > 33% were classified as poor-responders based on histological evaluation.
In the PT analysis, 10 patients were classified as PT well-responders and 8 as PT poor-responders. All post-treatment metabolic parameters, except MTV, were significantly lower in well-responders compared to poor-responders. The %ΔMTV, %ΔTLG were significantly higher in the poor-responder group (all P < 0.05). ROC curves indicated %ΔMTV exhibited optimum performance in predicting well-responders, with an AUC of 0.875 (cut-off: -31.01). Furthermore, %ΔMTV significantly predicted patients' recurrence-free survival (RFS) (P < 0.1). In the LN analysis, 7 LNs were classified as well-responders and 10 as poor-responders. Pre-treatment SUL, SUL were significantly lower in poor-responders compared to well-responders. Post-treatment MTV and all percentage changes in parameters were significantly higher in the poor-responder group (all P < 0.05). Receiver operating characteristic curve (ROC) analysis indicated %ΔTLG had excellent predictive performance for well-responders, with an AUC of 1.000 (cut-off: -7.5). However, there was no significant correlation between the metabolic response evaluations for PTs and LNs.
The metabolic parameters of [F]FDG PET/CT, particularly %ΔMTV and %ΔTLG, could effectively predict well-responders among both PTs and LNs to neoadjuvant PD-L1 blockade monotherapy in LA-ESCC, which may facilitate personalized immunotherapy and serve as a stratification tool in future larger-scale studies.
探讨2-[18F]-氟-2-脱氧-D-葡萄糖（[F]FDG）PET/CT在评估局部晚期食管鳞状细胞癌（LA-ESCC）患者新辅助程序性死亡配体1（PD-L1）阻断单药治疗后原发肿瘤（PT）和淋巴结（LN）反应方面的预测价值。
在单臂1b期NATION-1907试验（NCT04215471）中，23例LA-ESCC患者接受了两个周期的新辅助PD-L1阻断剂阿得贝利单抗治疗，随后接受手术。其中，18例患者在免疫治疗前和手术前均接受了[F]FDG PET/CT扫描。记录PT和LN的基于去脂体重校正的标准化摄取值（SUL）衍生参数，包括SUL和SUL。按照欧洲核医学协会（EANM）指南，分别使用SUL的41%和50%的阈值对大于1cm的病变进行分割，计算代谢肿瘤体积（MTV）和总病变糖酵解（TLG）。还记录了所有代谢参数的百分比变化。根据组织学评估，残留存活肿瘤≤33%被分类为良好反应者，而残留存活肿瘤>33%被分类为不良反应者。
在PT分析中，10例患者被分类为PT良好反应者，8例为PT不良反应者。与不良反应者相比，良好反应者除MTV外的所有治疗后代谢参数均显著降低。不良反应者组的%ΔMTV、%ΔTLG显著更高（均P<0.05）。受试者工作特征曲线（ROC）表明，%ΔMTV在预测良好反应者方面表现最佳，曲线下面积（AUC）为0.875（截断值：-31.01）。此外，%ΔMTV显著预测患者的无复发生存期（RFS）（P<0.1）。在LN分析中，7个LN被分类为良好反应者，10个为不良反应者。与良好反应者相比，不良反应者的治疗前SUL、SUL显著更低。不良反应者组的治疗后MTV和所有参数的百分比变化均显著更高（均P<0.05）。受试者操作特征曲线（ROC）分析表明，%ΔTLG对良好反应者具有出色的预测性能，AUC为1.000（截断值：-7.5）。然而，PT和LN的代谢反应评估之间没有显著相关性。
[F]FDG PET/CT的代谢参数，特别是%ΔMTV和%ΔTLG，可有效预测LA-ESCC患者中PT和LN对新辅助PD-L1阻断单药治疗的良好反应者，这可能有助于个性化免疫治疗，并在未来大规模研究中作为分层工具。
