Yong Wang1,2, Ningning Luo3, Ye Gao4, Yaqing Wu3, Xueting Qin2, Yingxue Qi3, Tingting Sun3, Rongjie Tao2, Chuang Qi3, Baoyan Liu5, Shuanghu Yuan6,7. 1. Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China. 2. 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. 3. The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd; Nanjing Simcere Medical Laboratory Science Co., Ltd; The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, People's Republic of China. 4. Department of Neurosurgery, Zhangqiu District People's Hospital, Jinan, Shandong, People's Republic of China. 5. Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, No. 18877 Jingshi Road, Jinan, 250062, Shandong, People's Republic of China. liubaoyan114@163.com. 6. Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China. yuanshuanghu@sina.com. 7. 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. yuanshuanghu@sina.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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: Clinical trial registration number: NCT03029065.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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: Clinical trial registration number: NCT03029065.
Authors: Lindsay Angus; John W M Martens; Martin J van den Bent; Peter A E Sillevis Smitt; Stefan Sleijfer; Agnes Jager Journal: Neuro Oncol Date: 2019-03-18 Impact factor: 12.300
Authors: Marc Chamberlain; Larry Junck; Dieta Brandsma; Riccardo Soffietti; Roberta Rudà; Jeffrey Raizer; Willem Boogerd; Sophie Taillibert; Morris D Groves; Emilie Le Rhun; Julie Walker; Martin van den Bent; Patrick Y Wen; Kurt A Jaeckle Journal: Neuro Oncol Date: 2017-04-01 Impact factor: 12.300