The First Central Clinical School, Tianjin Medical University, Tianjin, China.
Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China.
Cancer Med. 2024 Sep;13(18):e70216. doi: 10.1002/cam4.70216.
To investigate the value of 2-deoxy-18f-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I-IV NSCLC.
Blood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F-FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUV), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes.
There were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38-89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10-108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty-four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUV, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = -2.188 p = 0.039) and mixed CTCs (Z = -3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I-IV NSCLC, with a higher number of those who developed distant metastases than those who had non-distant metastases. Epithelial CTCs correlated with SUV (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUV (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUV (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I-II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate-late group (Stage III-IV).
Both FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUV and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUV and SUL, and total CTCs showed stronger correlations with SUV, SUL, MTV, and TLG in Stage I-II NSCLC. Only mesenchymal CTCs in Stage III-IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs.
探讨 2-脱氧-18f-氟代脱氧葡萄糖（18F-FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）和循环肿瘤细胞（CTC）在鉴别良性肺部疾病和非小细胞肺癌（NSCLC）患者中的作用。探索 I-IV 期 NSCLC 患者中 CTC 表型异质性及其与 FDG 摄取的相关性。
采集良性肺部疾病患者和原发性 NSCLC 患者的血样，用于检测 CTC 及其亚型（上皮型、混合型和间充质型），并分析 18F-FDG PET/CT 肿瘤代谢参数，包括最大标准化摄取值（SUV）、标准摄取值（SUL）、原发性病变的代谢肿瘤体积（MTV）、原发性病变的总糖酵解量（TLG）。还收集了包括年龄、性别、吸烟史、肿瘤大小、TNM 分期和病理类型在内的临床数据。比较了两种方法单独和联合用于鉴别良恶性的诊断价值。最后，比较了不同分期 NSCLC 患者 CTC 及其亚型的差异，并对 FDG 代谢参数与 CTC 亚型进行了相关性分析。
共纳入 65 例肺部疾病患者，其中 12 例为良性肺部疾病患者，53 例为 NSCLC 患者。患者平均年龄为 67±10（38-89）岁，其中 27 例为女性，38 例为男性。31 例（22 名男性和 9 名女性）有长期吸烟史。所有单个病变最大直径的平均大小为 36±22mm，范围为 10-108mm。12 例良性疾病中有 7 例为炎症性肉芽肿性病变，5 例为炎症性假瘤。53 例 NSCLC 中有 24 例为腺癌，29 例为鳞癌。53 例 NSCLC 患者中，12 例为 I 期，10 例为 II 期，17 例为 III 期，14 例为 IV 期。SUV、SUL、MTV、TLG、总 CTC、上皮型 CTC 和混合型 CTC 均对良恶性具有鉴别诊断价值。TLG 联合混合型 CTCs 在统计学上与其他所有诊断方法均有差异（p<0.05），且高于其他任何诊断标准。在良性与 I 期 NSCLC 的鉴别诊断中，只有总 CTC（Z=-2.188，p=0.039）和混合型 CTCs（Z=-3.020，p=0.014）具有一定的诊断效能，且两者之间无统计学差异（p=0.480）。仅在 I-IV 期 NSCLC 中，间充质型 CTC 数量在发生远处转移的患者中更高，而非远处转移的患者。上皮型 CTCs 与 SUV（r=0.333，p=0.015）和 SUL（r=0.374，p=0.006）相关。间充质型 CTCs 与 MTV（r=0.342，p=0.018）和 TLG（r=0.319，p=0.02）相关。进一步的亚组分析显示，上皮型 CTCs 与 SUV（r=0.543，p=0.009）和 SUL（r=0.552，p=0.008）相关，总 CTCs 与 SUV（r=0.622，p=0.003）、SUL（r=0.652，p=0.003）、MTV（r=0.460，p=0.031）和 TLG（r=0.472，p=0.027）相关，在早期组（I-II 期）。仅间充质型 CTCs 与 MTV（r=0.369，p=0.041）和 TLG（r=0.415，p=0.02）在中晚期组（III-IV 期）相关。
18F-FDG PET 代谢参数和 CTCs 均对 NSCLC 具有诊断价值，联合 TLG 与混合型 CTCs 可提高其诊断效能。总 CTCs 和混合型 CTCs 比 FDG PET 更能鉴别良性病变与 I 期 NSCLC。在 NSCLC 患者中，上皮型 CTCs 与 SUV 和 SUL 呈正相关，而间充质型 CTCs 与 MTV 和 TLG 相关。此外，在 I-II 期 NSCLC 中，上皮型 CTCs 与 SUV 和 SUL 相关性更强，总 CTCs 与 SUV、SUL、MTV 和 TLG 相关性更强。仅在 III-IV 期 NSCLC 中，间充质型 CTCs 与 MTV 和 TLG 相关。IV 期 NSCLC 患者中存在更多的间充质型 CTCs。
