Purpose

To investigate the predictive value of 2-[18F]-fluoro-2-deoxy-D-glucose ([¹⁸F]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).

Methods

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 [¹⁸F]FDG PET/CT scans both before immunotherapy and prior to surgery. Standardized uptake value corrected for lean body mass (SUL)-derived parameters, including SUL_max and SUL_peak, were documented for PTs and LNs. Lesions > 1cm³ were segmented using thresholds of 41% and 50% of SUL_max, 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.

Results

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 %ΔMTV₄₁ exhibited optimum performance in predicting well-responders, with an AUC of 0.875 (cut-off: -31.01). Furthermore, %ΔMTV₄₁ 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_max, SUL_peak were significantly lower in poor-responders compared to well-responders. Post-treatment MTV₅₀ 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 %ΔTLG₅₀ 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.

Conclusion

The metabolic parameters of [¹⁸F]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.

中文翻译：

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[18楼]FDG PET/CT 预测局部晚期食管鳞状细胞癌患者新辅助 PD-L1 阻断单药治疗反应的初步研究

 目的

探讨 2-[18F]-氟-2-脱氧-D-葡萄糖 （[¹⁸F]FDG） PET/CT 对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） 反应的预测价值。

 方法

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 Adebrelimab，然后进行了手术。其中，18 例患者在免疫治疗前和手术前接受了 [¹⁸F]FDG PET/CT 扫描。记录了针对瘦体重 （SUL） 衍生参数（包括 SUL_max和 SUL_峰值）校正的标准化摄取值，用于 PTs 和 LNs。根据欧洲核医学协会 （EANM） 指南，分别使用 SUL_max 的 41% 和 50% 的阈值对病变 > 1cm³ 进行分割，并计算代谢肿瘤体积 （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。残余活肿瘤 ≤ 33% 被归类为反应良好，而残余活肿瘤 > 33% 根据组织学评估被归类为反应不佳。

 结果

在 PT 分析中，10 例患者被归类为 PT 反应良好者，8 例被归类为 PT 反应不佳者。与反应不佳的患者相比，反应良好的患者的所有治疗后代谢参数（MTV 除外）均显著降低。反应不佳组的 %ΔMTV 、 %ΔTLG 显著升高 （均 P < 0.05）。ROC 曲线表明 %ΔMTV₄₁ 在预测反应良好的受试者方面表现出最佳性能，AUC 为 0.875 （截断值： -31.01）。此外，%ΔMTV₄₁ 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 被归类为反应良好者，10 个被归类为反应不佳者。与反应良好的患者相比，反应不佳的患者的治疗前 SUL_max、SUL_峰值显着降低。治疗后 MTV₅₀ 和参数的所有百分比变化在反应不佳的组中均显著升高 （均 P < 0.05）。受试者工作特征曲线 （ROC） 分析表明 %ΔTLG₅₀ 对反应良好的患者具有出色的预测性能，AUC 为 1.000 （截断值： -7.5）。然而，PTs 和 LNs 的代谢反应评估之间没有显着相关性。

 结论

[¹⁸F]FDG PET/CT 的代谢参数，特别是 %ΔMTV 和 %ΔTLG，可以有效预测 PTs 和 LNs 对 LA-ESCC 新辅助 PD-L1 阻断单药治疗的反应良好，这可能促进个性化免疫治疗，并作为未来更大规模研究的分层工具。