Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis
Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001544 |
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| author | Sheng-Kai Liang Wei-Yu Liao Jin-Yuan Shih Chia-Lin Hsu Ching-Yao Yang Shang-Gin Wu Yen-Ting Lin Yueh-Feng Wen Lun-Che Chen Yen-Fu Chen Ya-Fang Chen Yen-Heng Lin Chong-Jen Yu |
| author_facet | Sheng-Kai Liang Wei-Yu Liao Jin-Yuan Shih Chia-Lin Hsu Ching-Yao Yang Shang-Gin Wu Yen-Ting Lin Yueh-Feng Wen Lun-Che Chen Yen-Fu Chen Ya-Fang Chen Yen-Heng Lin Chong-Jen Yu |
| author_sort | Sheng-Kai Liang |
| collection | DOAJ |
| description | Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM. These patients underwent CSF cfDNA analysis using a 118-gene targeted panel for NGS, with comprehensive clinical data collected. Among 25 enrolled patients, 22 (88.0 %) had EGFR mutations, while three (12.0 %) had EML4-ALK fusion, KIF5B-RET fusion, and ERBB2 A775_G776insSVMA. CSF cfDNA sequencing of 27 samples (from 25 patients) all confirmed their original driver mutations. Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3–11.6) from the initiation of ITP to death. Among them, ten individuals (55.6 %) survived beyond 6 months. Notably, MET copy number gain (CNG) correlated significantly with survival time exceeding 6 months after ITP (p = 0.007). The coexistence of EGFR T790M and EGFR-independent resistance alterations was associated with shorter survival times after ITP, with a median survival time of 1.9 months compared to 9.9 months for those without EGFR T790M (p = 0.010). Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. MET CNG positively impacts survival for ITP recipients, whereas the coexistence of EGFR T790M and EGFR-independent resistance mechanisms leads to poor outcomes. |
| format | Article |
| id | doaj-art-b3d442c082314d269e570eaf7f0bd5b4 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-b3d442c082314d269e570eaf7f0bd5b42025-02-03T04:16:34ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101113Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasisSheng-Kai Liang0Wei-Yu Liao1Jin-Yuan Shih2Chia-Lin Hsu3Ching-Yao Yang4Shang-Gin Wu5Yen-Ting Lin6Yueh-Feng Wen7Lun-Che Chen8Yen-Fu Chen9Ya-Fang Chen10Yen-Heng Lin11Chong-Jen Yu12Department of Medicine, National Taiwan University Cancer Center, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, No. 7 Chung Shan South Rd, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Medicine, National Taiwan University Cancer Center, Taipei, TaiwanDepartment of Medicine, National Taiwan University Cancer Center, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, TaiwanDepartment of Medical Imaging, National Taiwan University Hospital, Taipei, TaiwanDepartment of Medical Imaging, National Taiwan University Hospital, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, TaiwanLeptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM. These patients underwent CSF cfDNA analysis using a 118-gene targeted panel for NGS, with comprehensive clinical data collected. Among 25 enrolled patients, 22 (88.0 %) had EGFR mutations, while three (12.0 %) had EML4-ALK fusion, KIF5B-RET fusion, and ERBB2 A775_G776insSVMA. CSF cfDNA sequencing of 27 samples (from 25 patients) all confirmed their original driver mutations. Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3–11.6) from the initiation of ITP to death. Among them, ten individuals (55.6 %) survived beyond 6 months. Notably, MET copy number gain (CNG) correlated significantly with survival time exceeding 6 months after ITP (p = 0.007). The coexistence of EGFR T790M and EGFR-independent resistance alterations was associated with shorter survival times after ITP, with a median survival time of 1.9 months compared to 9.9 months for those without EGFR T790M (p = 0.010). Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. MET CNG positively impacts survival for ITP recipients, whereas the coexistence of EGFR T790M and EGFR-independent resistance mechanisms leads to poor outcomes.http://www.sciencedirect.com/science/article/pii/S1476558624001544Non-small cell lung cancer (NSCLC)Leptomeningeal metastasisCell-free DNA (cfDNA)Cerebrospinal fluid (CSF)Intrathecal pemetrexed |
| spellingShingle | Sheng-Kai Liang Wei-Yu Liao Jin-Yuan Shih Chia-Lin Hsu Ching-Yao Yang Shang-Gin Wu Yen-Ting Lin Yueh-Feng Wen Lun-Che Chen Yen-Fu Chen Ya-Fang Chen Yen-Heng Lin Chong-Jen Yu Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis Neoplasia: An International Journal for Oncology Research Non-small cell lung cancer (NSCLC) Leptomeningeal metastasis Cell-free DNA (cfDNA) Cerebrospinal fluid (CSF) Intrathecal pemetrexed |
| title | Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis |
| title_full | Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis |
| title_fullStr | Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis |
| title_full_unstemmed | Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis |
| title_short | Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis |
| title_sort | clinical utility and predictive value of cerebrospinal fluid cell free dna profiling in non small cell lung cancer patients with leptomeningeal metastasis |
| topic | Non-small cell lung cancer (NSCLC) Leptomeningeal metastasis Cell-free DNA (cfDNA) Cerebrospinal fluid (CSF) Intrathecal pemetrexed |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001544 |
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