Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
German Cancer Consortium, Partner Site University Hospital Essen, and German Cancer Research Center, Essen, Germany.
J Nucl Med. 2022 Jan;63(1):89-95. doi: 10.2967/jnumed.121.262096. Epub 2021 Apr 30.
Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the Ga-FAPI PET prospective observational trial. Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical Ga-FAPI PET were eligible for enrollment into the Ga-FAPI PET observational trial. Of these patients, 43 also underwent F-FDG PET. The primary study endpoint was the association between Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. The primary endpoint was met, and the association between Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman = 0.43; = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in Ga-FAPI and F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, Ga-FAPI PET resulted in an upstaging compared with F-FDG PET. Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after Ga-FAPI PET. We confirm an association between tumoral Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.
骨和软组织肉瘤在肿瘤细胞和相关成纤维细胞上表达成纤维细胞激活蛋白（FAP）。因此，FAP 是一个很有前途的治疗和诊断靶点。新型放射性标记的 FAP 抑制剂（例如，Ga-FAPI-46）在肉瘤患者的 PET 上显示出高肿瘤摄取率。在这里，我们报告了 Ga-FAPI PET 前瞻性观察性试验的终点。47 名接受骨或软组织肉瘤临床 Ga-FAPI PET 的患者有资格参加 Ga-FAPI PET 观察性试验。其中 43 名患者还接受了 F-FDG PET。主要研究终点是 Ga-FAPI PET 摄取强度与组织病理学 FAP 表达之间的相关性，用 Spearman 相关分析。次要终点是检测率、阳性预测值（PPV）、读者间可重复性和管理变化。数据集由 2 位盲法读者解读。主要终点达到，Ga-FAPI PET 摄取强度与组织病理学 FAP 表达之间存在显著相关性（Spearman = 0.43； = 0.03）。通过组织病理学验证，每位患者的 PPV 为 1.00（95%CI，0.87-1.00），每位患者的 PPV 为 0.97（95%CI，0.84-1.00）。在有组织病理学验证的情况下，28 例（96%）确诊患者和 34 例（94%）确诊部位的 27 例和 32 例为 PET 阳性，这导致每位患者的 SE 为 0.96（95%CI，0.82-1.00）和每位患者的 SE 为 0.94（95%CI，0.80-0.99）。Ga-FAPI 和 F-FDG PET 的每位患者的检测率分别为 76.6%和 81.4%。在 8 名（18.6%）患者中，Ga-FAPI PET 与 F-FDG PET 相比导致分期升高。Ga-FAPI PET 读者对定义的区域显示出实质性到几乎完美的一致性（Fleiss κ：主要 κ = 0.78，局部淋巴结 κ = 0.54，远处淋巴结 κ = 0.91，肺 κ = 0.86，骨 κ = 0.69，其他 κ = 0.65）。Ga-FAPI PET 后 13 名（30%）患者的临床管理发生了变化。我们确认了肉瘤患者中肿瘤 Ga-FAPI PET 摄取强度与组织病理学 FAP 表达之间的相关性。此外，通过盲法阅读和独立的组织病理学验证，Ga-FAPI PET 对肉瘤分期具有较高的 PPV 和敏感性。
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