Darlix Amélie, Cayrefourcq Laure, Pouderoux Stéphane, Menjot de Champfleur Nicolas, Bievelez Alexis, Jacot William, Leaha Cristina, Thezenas Simon, Alix-Panabières Catherine
Department of Medical Oncology, Institut Régional du Cancer de Montpellier, University of Montpellier, Montpellier, France.
Institut de Génomique Fonctionnelle, INSERM, CNRS, University of Montpellier, Montpellier, France.
Clin Chem. 2022 Oct 6;68(10):1311-1322. doi: 10.1093/clinchem/hvac127.
The diagnosis of breast cancer (BC)-related leptomeningeal metastases (LM) relies on the detection of tumor cells in cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, the sensitivity of this technique is low. Our goal was to evaluate whether circulating tumor cell (CTC) detection in CSF using the CellSearch® system could be used for LM diagnosis.
This prospective, monocentric study included adult patients with suspected BC-related LM. The clinical sensitivity and specificity of CTC detection in CSF for LM diagnosis were calculated relative to conventional CSF cytology.
Forty-nine eligible patients were included and 40 were evaluable (CTC detection technical failure: n = 8, eligibility criteria failure: n = 1). Cytology was positive in 18/40 patients. CTCs were detected in these 18 patients (median: 5824 CTC, range: 93 to 45052) and in 5/22 patients with negative cytology (median: 2 CTC, range: 1 to 44). The detection of ≥1 CSF CTC was associated with a clinical sensitivity of 100% (95% CI, 82.4-100) and a specificity of 77.3% (95% CI, 64.3-90.3) for LM diagnosis. HER2+ CTCs were detected in the CSF of 40.6% of patients with HER2- BC (median: 500 CTC, range: 13 to 28 320).
The clinical sensitivity of CTC detection in CSF with the CellSearch® system for LM diagnosis is higher than that of CSF cytology. CTC detection in patients with negative cytology, however, must be further investigated. The finding of HER2+ CTCs in patients with HER2- BC suggests that the HER2 status of LM should be evaluated to increase the treatment opportunities for these patients.
乳腺癌（BC）相关软脑膜转移（LM）的诊断依赖于使用传统细胞学方法（金标准）检测脑脊液（CSF）中的肿瘤细胞。然而，该技术的敏感性较低。我们的目标是评估使用CellSearch®系统检测脑脊液中的循环肿瘤细胞（CTC）是否可用于LM的诊断。
这项前瞻性、单中心研究纳入了疑似BC相关LM的成年患者。相对于传统脑脊液细胞学检查，计算脑脊液中CTC检测对LM诊断的临床敏感性和特异性。
纳入49例符合条件的患者，40例可评估（CTC检测技术失败：n = 8，不符合纳入标准：n = 1）。40例患者中18例细胞学检查呈阳性。这18例患者中检测到CTC（中位数：5824个CTC，范围：93至45052），22例细胞学检查阴性的患者中有5例检测到CTC（中位数：2个CTC，范围：1至44）。检测到≥1个脑脊液CTC对LM诊断的临床敏感性为100%（95%CI，82.4 - 100），特异性为77.3%（95%CI，64.3 - 90.3）。40.6%的HER2阴性BC患者的脑脊液中检测到HER2阳性CTC（中位数：500个CTC，范围：13至28320）。
使用CellSearch®系统检测脑脊液中的CTC对LM诊断的临床敏感性高于脑脊液细胞学检查。然而，细胞学检查阴性患者中CTC检测的情况仍需进一步研究。HER2阴性BC患者中发现HER2阳性CTC表明，应评估LM的HER2状态，以增加这些患者的治疗机会。
