Wang Yong, Luo Ningning, Gao Ye, Wu Yaqing, Qin Xueting, Qi Yingxue, Sun Tingting, Tao Rongjie, Qi Chuang, Liu Baoyan, Yuan Shuanghu
Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, No.440. Jiyan Road, Jinan, 250117, Shandong, People's Republic of China.
J Cancer Res Clin Oncol. 2023 May;149(5):1679-1690. doi: 10.1007/s00432-022-04053-7. Epub 2022 May 18.
Leptomeningeal metastases (LMs) are highly invasive which leads to poor prognosis, but the accurate diagnosis of LM is challenging. It is necessary to investigate more advanced diagnostic methods to realize precision medicine. The main purpose of this study was to select a more effective method for the auxiliary diagnosis of LM by comparing various detection methods. The secondary purpose was to explore the value of cerebrospinal fluid (CSF) tumor markers (TMs) and circulating tumor DNA (ctDNA) testing in guiding clinical treatment.
TMs in serum and CSF of patients were detected by chemiluminescence. The ctDNA of CSF and plasma were detected by the next-generation sequencing (NGS) technology.
In total, 54 tumor patients participated in this study, in which 39 with LM and 15 without LM (8 with parenchymal tumor and 7 without brain metastasis). The results showed that the sensitivity and accuracy of CSF cytology isolated during the first lumbar puncture were 0.31 (95% CI 0.17-0.48) and 0.50 (95% CI 0.36-0.64), respectively. The sensitivity and accuracy of CSF_CEA were 0.71 (95% CI 0.54-0.85) and 0.78 (95% CI 0.64-0.89), which were better than those of CSF_NSE and CSF_CFRA-211. The sensitivity and accuracy of CSF_ctDNA were 0.92 (95% CI 0.79-0.98) and 0.91 (95% CI 0.80-0.97), significantly higher than that of CSF cytology (P < 0.01). The sensitivity and accuracy of CSF_CEA combined with CSF_ctDNA were 0.97 (95% CI, 0.87-1.00) and 0.94 (95% CI 0.85-0.99), which were significantly higher than the traditional methods CSF cytology (P < 0.01). For LM patients with hydrocephalus, the sensitivity of CSF ctDNA even achieved 100% (14/14).
CSF_CEA combined with CSF_ctDNA could be used to accurately distinguish patients with LM from those with no brain metastasis and from those with parenchymal tumors. CSF_ctDNA testing reveals a unique mutation profile for patients with LM. Dynamic detection of CSF TM and ctDNA can better predict the efficacy and reveal the cause of drug resistance to guide subsequent treatment.
Clinical trial registration number: NCT03029065.
软脑膜转移（LMs）具有高度侵袭性，预后较差，但LMs的准确诊断具有挑战性。有必要研究更先进的诊断方法以实现精准医疗。本研究的主要目的是通过比较各种检测方法，选择一种更有效的方法辅助诊断LMs。次要目的是探讨脑脊液（CSF）肿瘤标志物（TMs）和循环肿瘤DNA（ctDNA）检测在指导临床治疗中的价值。
采用化学发光法检测患者血清和CSF中的TMs。采用下一代测序（NGS）技术检测CSF和血浆中的ctDNA。
共有54例肿瘤患者参与本研究，其中39例有LMs，15例无LMs（8例有实质肿瘤，7例无脑转移）。结果显示，首次腰椎穿刺采集的CSF细胞学检查的敏感性和准确性分别为0.31（95%CI 0.17 - 0.48）和0.50（95%CI 0.36 - 0.64）。CSF_CEA的敏感性和准确性分别为0.71（95%CI 0.54 - 0.85）和0.78（95%CI 0.64 - 0.89），优于CSF_NSE和CSF_CFRA - 211。CSF_ctDNA的敏感性和准确性分别为0.92（95%CI 0.79 - 0.98）和0.91（95%CI 0.80 - 0.97），显著高于CSF细胞学检查（P < 0.01）。CSF_CEA联合CSF_ctDNA的敏感性和准确性分别为0.97（95%CI，0.87 - 1.00）和0.94（95%CI 0.85 - 0.99），显著高于传统方法CSF细胞学检查（P < 0.01）。对于伴有脑积水的LMs患者，CSF ctDNA的敏感性甚至达到100%（14/14）。
CSF_CEA联合CSF_ctDNA可用于准确区分LMs患者与无脑转移及实质肿瘤患者。CSF_ctDNA检测揭示了LMs患者独特的突变谱。动态检测CSF TM和ctDNA可以更好地预测疗效并揭示耐药原因，以指导后续治疗。
临床试验注册号：NCT03029065。
