Abstract

Purpose

Mediastinal nodal staging is crucial for surgical candidate selection in non-small cell lung cancer (NSCLC), but conventional imaging has limitations often necessitating invasive staging. We investigated the additive clinical value of fibroblast activation protein inhibitor (FAPI) PET/CT, an imaging technique targeting fibroblast activation protein, for mediastinal nodal staging of NSCLC.

Methods

In this prospective pilot study, we enrolled patients scheduled for surgical resection of NSCLC based on specific criteria designed to align with indications for invasive staging procedures. Patients were included when meeting at least one of the following: (1) presence of FDG-positive N2 lymph nodes, (2) clinical N1 stage, (3) central tumor location or tumor diameter of ≥ 3 cm, and (4) adenocarcinoma exhibiting high FDG uptake. [⁶⁸Ga]FAPI-46 PET/CT was performed before surgery after a staging workup including [¹⁸F]FDG PET/CT. The diagnostic accuracy of [⁶⁸Ga]FAPI-46 PET/CT for “N2” nodes was assessed through per-patient visual assessment and per-station quantitative analysis using histopathologic results as reference standards.

Results

Twenty-three patients with 75 nodal stations were analyzed. Histopathologic examination confirmed that nine patients (39.1%) were N2-positive. In per-patient assessment, [⁶⁸Ga]FAPI-46 PET/CT successfully identified metastasis in eight patients (sensitivity 0.89 (0.52–1.00)), upstaging three patients compared to [¹⁸F]FDG PET/CT. [¹⁸F]FDG PET/CT detected FDG-avid nodes in six (42.8%) of 14 N2-negative patients. Among them, five were considered non-metastatic based on calcification and distribution pattern, and one was considered metastatic. In contrast, [⁶⁸Ga]FAPI-46 PET/CT correctly identified all non-metastatic patients solely based on tracer avidity. In per-station analysis, [⁶⁸Ga]FAPI-46 PET/CT discriminated metastasis more effectively compared to [¹⁸F]FDG PET/CT-based (AUC of ROC curve 0.96 (0.88–0.99) vs. 0.68 (0.56–0.78), P < 0.001).

Conclusion

[⁶⁸Ga]FAPI-46 PET/CT holds promise as an imaging tool for preoperative mediastinal nodal staging in NSCLC, with improved sensitivity and the potential to reduce false-positive results, optimizing the need for invasive staging procedures.

中文翻译：

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使用 [68Ga]FAPI-46 PET/CT 对非小细胞肺癌纵隔淋巴结进行术前评估：一项前瞻性试点研究

摘要

目的

纵隔淋巴结分期对于非小细胞肺癌 (NSCLC) 的手术候选者选择至关重要，但传统影像学具有局限性，通常需要侵入性分期。我们研究了成纤维细胞活化蛋白抑制剂 (FAPI) PET/CT（一种针对成纤维细胞活化蛋白的成像技术）对于 NSCLC 纵隔淋巴结分期的附加临床价值。

方法

在这项前瞻性试点研究中，我们根据旨在与侵入性分期手术适应症相一致的特定标准，招募了计划进行非小细胞肺癌手术切除的患者。满足以下至少一项条件的患者被纳入：(1) 存在 FDG 阳性 N2 淋巴结，(2) 临床 N1 分期，(3) 肿瘤位于中心或肿瘤直径≥ 3 cm，以及 (4) 腺癌表现出高 FDG 吸收率。^{在包括[ 18} F]FDG PET/CT在内的分期检查后，在手术前进行[ ⁶⁸ Ga]FAPI-46 PET/CT。使用组织病理学结果作为参考标准，通过每名患者的视觉评估和每站的定量分析来评估[ ⁶⁸ Ga]FAPI-46 PET/CT 对“N2”淋巴结的诊断准确性。

结果

对 23 名患者的 75 个节点进行了分析。组织病理学检查证实9名患者（39.1%）为N2阳性。在每个患者的评估中，[ ⁶⁸ Ga]FAPI-46 PET/CT 成功识别了 8 名患者的转移（敏感性 0.89 (0.52–1.00)），与 [ ¹⁸ F]FDG PET/CT 相比，提高了 3 名患者的分期。[ ¹⁸ F]FDG PET/CT 在 14 名 N2 阴性患者中的 6 名 (42.8%) 中检测到 FDG 亲和淋巴结。其中，根据钙化和分布模式，5 例被认为是非转移性的，1 例被认为是转移性的。相比之下，[ ⁶⁸ Ga]FAPI-46 PET/CT 仅根据示踪剂亲和力正确识别了所有非转移患者。在每站分析中，与基于[ ¹⁸ F]FDG PET/CT 的相比， [ ⁶⁸ Ga]FAPI-46 PET/CT 更有效地区分转移（ROC 曲线的 AUC 0.96 (0.88–0.99) vs. 0.68 (0.56–0.78) ），P < 0.001）。

结论

[ ⁶⁸ Ga]FAPI-46 PET/CT有望作为非小细胞肺癌术前纵隔淋巴结分期的成像工具，具有更高的灵敏度和减少假阳性结果的潜力，优化侵入性分期程序的需求。