Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods
Abstract Background Brain metastasis is a common and serious complication in patients with non-small cell lung cancer (NSCLC), often associated with poor prognosis. While traditional diagnostic approaches such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology are commonly us...
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BMC
2025-07-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14583-1 |
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| author | Oluwatobi O. Olayode Blessing T. Ogunoye Emmanuel Olusola Oladeji Oluwafemi E. Olayinka Tolulope J. Oladosu |
| author_facet | Oluwatobi O. Olayode Blessing T. Ogunoye Emmanuel Olusola Oladeji Oluwafemi E. Olayinka Tolulope J. Oladosu |
| author_sort | Oluwatobi O. Olayode |
| collection | DOAJ |
| description | Abstract Background Brain metastasis is a common and serious complication in patients with non-small cell lung cancer (NSCLC), often associated with poor prognosis. While traditional diagnostic approaches such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology are commonly used for detection, these methods have notable limitations. Circulating tumor DNA (ctDNA) in CSF has been reported as a superior alternative. This study evaluates the diagnostic test accuracy of CSF ctDNA for CNS metastases detection in patients with NSCLC, in comparison to CSF cytology, while also examining its potential prognostic value. Methods A systematic search was conducted to identify studies that reported CSF ctDNA detection in NSCLC patients with brain or leptomeningeal metastases. Pooled detection rates, sensitivity, specificity, and diagnostic odds ratios were meta-analyzed. Heterogeneity and publication bias were assessed using standard statistical methods. Subgroup and sensitivity analysis were applied to identify and address source of high heterogeneity. Results Twenty-six studies were included. The pooled detection rate of CSF ctDNA (86%, 95% CI: 0.79–0.91) was significantly higher than CSF cytology (60%, 95% CI: 36% % 81%). Diagnostic test accuracy analysis for CSF ctDNA showed high pooled sensitivity (91.8%, 95% CI: 74.2%–97.8%), specificity (93.5%, 95% CI: 76.7% – 98.5%) and diagnostic odds ratio (DOR) (93.51%, 95% CI: 13.85–631.44). Additionally, CSF ctDNA detected clinically relevant mutations that correlated with poorer overall survival, highlighting its prognostic potential. Conclusion CSF ctDNA demonstrates superior diagnostic accuracy for detecting CNS metastases in NSCLC compared to CSF cytology. Its molecular insights may support earlier detection and inform personalized treatment strategies. However, further validation in clinical settings is required. |
| format | Article |
| id | doaj-art-ee5b7783a606409fb730e1cd0bb604f3 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-ee5b7783a606409fb730e1cd0bb604f32025-08-20T03:05:13ZengBMCBMC Cancer1471-24072025-07-0125112210.1186/s12885-025-14583-1Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methodsOluwatobi O. Olayode0Blessing T. Ogunoye1Emmanuel Olusola Oladeji2Oluwafemi E. Olayinka3Tolulope J. Oladosu4Department of Surgery, Obafemi Awolowo UniversityDepartment of Surgery, Obafemi Awolowo UniversitySurgery Interest Group of AfricaDepartment of Surgery, Obafemi Awolowo UniversityDepartment of Surgery, Obafemi Awolowo UniversityAbstract Background Brain metastasis is a common and serious complication in patients with non-small cell lung cancer (NSCLC), often associated with poor prognosis. While traditional diagnostic approaches such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology are commonly used for detection, these methods have notable limitations. Circulating tumor DNA (ctDNA) in CSF has been reported as a superior alternative. This study evaluates the diagnostic test accuracy of CSF ctDNA for CNS metastases detection in patients with NSCLC, in comparison to CSF cytology, while also examining its potential prognostic value. Methods A systematic search was conducted to identify studies that reported CSF ctDNA detection in NSCLC patients with brain or leptomeningeal metastases. Pooled detection rates, sensitivity, specificity, and diagnostic odds ratios were meta-analyzed. Heterogeneity and publication bias were assessed using standard statistical methods. Subgroup and sensitivity analysis were applied to identify and address source of high heterogeneity. Results Twenty-six studies were included. The pooled detection rate of CSF ctDNA (86%, 95% CI: 0.79–0.91) was significantly higher than CSF cytology (60%, 95% CI: 36% % 81%). Diagnostic test accuracy analysis for CSF ctDNA showed high pooled sensitivity (91.8%, 95% CI: 74.2%–97.8%), specificity (93.5%, 95% CI: 76.7% – 98.5%) and diagnostic odds ratio (DOR) (93.51%, 95% CI: 13.85–631.44). Additionally, CSF ctDNA detected clinically relevant mutations that correlated with poorer overall survival, highlighting its prognostic potential. Conclusion CSF ctDNA demonstrates superior diagnostic accuracy for detecting CNS metastases in NSCLC compared to CSF cytology. Its molecular insights may support earlier detection and inform personalized treatment strategies. However, further validation in clinical settings is required.https://doi.org/10.1186/s12885-025-14583-1CSF ctDNABrain metastasesNSCLCLiquid biopsyDiagnostic accuracyBiomarker |
| spellingShingle | Oluwatobi O. Olayode Blessing T. Ogunoye Emmanuel Olusola Oladeji Oluwafemi E. Olayinka Tolulope J. Oladosu Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods BMC Cancer CSF ctDNA Brain metastases NSCLC Liquid biopsy Diagnostic accuracy Biomarker |
| title | Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods |
| title_full | Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods |
| title_fullStr | Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods |
| title_full_unstemmed | Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods |
| title_short | Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods |
| title_sort | cerebrospinal fluid circulating tumor dna ctdna as a biomarker for cns metastases in non small cell lung cancer nsclc a systematic review and meta analysis comparing csf ctdna and traditional methods |
| topic | CSF ctDNA Brain metastases NSCLC Liquid biopsy Diagnostic accuracy Biomarker |
| url | https://doi.org/10.1186/s12885-025-14583-1 |
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