Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases
BackgroundBrain metastases (BM), including brain parenchyma metastases (BPM) and leptomeningeal metastases (LM), are devastating metastatic complications in advanced cancer patients. Next-generation sequencing (NGS) is emerging as a new promising tool for profiling cancer mutation, which could facil...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1322635/full |
| _version_ | 1797359323120140288 |
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| author | Xiaocui Liu Xiaocui Liu Fengjun Mei Mei Fang Yaqiong Jia Yazhu Zhou Chenxi Li Panpan Tian Chufan Lu Guangrui Li Guangrui Li |
| author_facet | Xiaocui Liu Xiaocui Liu Fengjun Mei Mei Fang Yaqiong Jia Yazhu Zhou Chenxi Li Panpan Tian Chufan Lu Guangrui Li Guangrui Li |
| author_sort | Xiaocui Liu |
| collection | DOAJ |
| description | BackgroundBrain metastases (BM), including brain parenchyma metastases (BPM) and leptomeningeal metastases (LM), are devastating metastatic complications in advanced cancer patients. Next-generation sequencing (NGS) is emerging as a new promising tool for profiling cancer mutation, which could facilitate the diagnosis of cancer. This retrospective study aimed to investigate the molecular genetic characteristics of non-small cell lung cancer (NSCLC) patients with BPM and LM using NGS.MethodsCerebrospinal fluid (CSF) samples and paired plasma samples were collected from 37 patients of NSCLC-BM. We profiled genetic mutation characteristics using NGS from NSCLC-BM by comparing CSF circulating tumour DNA (ctDNA) with plasma ctDNA and primary tumour tissues.ResultsAmong the 37 patients with NSCLC-BM, 28 patients had LM with or without BPM, while 9 patients only had BPM. Driver and drug-resistant mutations in primary tumours with LM included: EGFR L858R (10, 35.7%), EGFR 19del (6, 21.4%), EGFR L858R+MET (1, 3.6%), EGFR L858R+S768I (1, 3.6%), ALK (2, 7.1%), ROS1 (1, 3.6%), negative (5, 17.9%), and unknown (2, 7.1%). In patients with NSCLC-LM, the detection rate and abundance of ctDNA in the CSF were significantly higher than those in paired plasma. The main driver mutations of NSCLC-LM remained highly consistent with those of the primary tumours, along with other unique mutations. Circulating tumour DNA was negative in the CSF samples of BPM patients. Patients with BMP had a higher ratio of EGFR 19del than L858R mutation (55.6% vs 11.1.%), whereas NSCLC patients with LM had a higher ratio of EGFR L858R than 19del mutation (50.0% vs 25.0%). Most patients with positive plasma ctDNA results were male (p = 0.058) and in an unstable state (p = 0.003).ConclusionOur study indicated that the CSF ctDNA detected by NGS may reflect the molecular characteristics and heterogeneity of NSCLC-LM. Timely screening of patients with NSCLC for CSF ctDNA, especially for patients with positive plasma ctDNA, may facilitate the early detection of LM. Furthermore, patients with the EGFR 19del may have a higher risk of developing BPM. |
| first_indexed | 2024-03-08T15:15:55Z |
| format | Article |
| id | doaj.art-10c4fa06c0e141eea60142ced3edf842 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-08T15:15:55Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-10c4fa06c0e141eea60142ced3edf8422024-01-10T11:02:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-01-011310.3389/fonc.2023.13226351322635Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastasesXiaocui Liu0Xiaocui Liu1Fengjun Mei2Mei Fang3Yaqiong Jia4Yazhu Zhou5Chenxi Li6Panpan Tian7Chufan Lu8Guangrui Li9Guangrui Li10Department of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Reproductive Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Infectious Diseases, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaBackgroundBrain metastases (BM), including brain parenchyma metastases (BPM) and leptomeningeal metastases (LM), are devastating metastatic complications in advanced cancer patients. Next-generation sequencing (NGS) is emerging as a new promising tool for profiling cancer mutation, which could facilitate the diagnosis of cancer. This retrospective study aimed to investigate the molecular genetic characteristics of non-small cell lung cancer (NSCLC) patients with BPM and LM using NGS.MethodsCerebrospinal fluid (CSF) samples and paired plasma samples were collected from 37 patients of NSCLC-BM. We profiled genetic mutation characteristics using NGS from NSCLC-BM by comparing CSF circulating tumour DNA (ctDNA) with plasma ctDNA and primary tumour tissues.ResultsAmong the 37 patients with NSCLC-BM, 28 patients had LM with or without BPM, while 9 patients only had BPM. Driver and drug-resistant mutations in primary tumours with LM included: EGFR L858R (10, 35.7%), EGFR 19del (6, 21.4%), EGFR L858R+MET (1, 3.6%), EGFR L858R+S768I (1, 3.6%), ALK (2, 7.1%), ROS1 (1, 3.6%), negative (5, 17.9%), and unknown (2, 7.1%). In patients with NSCLC-LM, the detection rate and abundance of ctDNA in the CSF were significantly higher than those in paired plasma. The main driver mutations of NSCLC-LM remained highly consistent with those of the primary tumours, along with other unique mutations. Circulating tumour DNA was negative in the CSF samples of BPM patients. Patients with BMP had a higher ratio of EGFR 19del than L858R mutation (55.6% vs 11.1.%), whereas NSCLC patients with LM had a higher ratio of EGFR L858R than 19del mutation (50.0% vs 25.0%). Most patients with positive plasma ctDNA results were male (p = 0.058) and in an unstable state (p = 0.003).ConclusionOur study indicated that the CSF ctDNA detected by NGS may reflect the molecular characteristics and heterogeneity of NSCLC-LM. Timely screening of patients with NSCLC for CSF ctDNA, especially for patients with positive plasma ctDNA, may facilitate the early detection of LM. Furthermore, patients with the EGFR 19del may have a higher risk of developing BPM.https://www.frontiersin.org/articles/10.3389/fonc.2023.1322635/fullnon-small cell lung cancer (NSCLC)leptomeningeal metastases (LM)brain parenchyma metastases (BPM)cerebrospinal fluid circulating tumour DNA (ctDNA)next generation sequencing |
| spellingShingle | Xiaocui Liu Xiaocui Liu Fengjun Mei Mei Fang Yaqiong Jia Yazhu Zhou Chenxi Li Panpan Tian Chufan Lu Guangrui Li Guangrui Li Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases Frontiers in Oncology non-small cell lung cancer (NSCLC) leptomeningeal metastases (LM) brain parenchyma metastases (BPM) cerebrospinal fluid circulating tumour DNA (ctDNA) next generation sequencing |
| title | Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases |
| title_full | Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases |
| title_fullStr | Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases |
| title_full_unstemmed | Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases |
| title_short | Cerebrospinal fluid ctDNA testing shows an advantage over plasma ctDNA testing in advanced non-small cell lung cancer patients with brain metastases |
| title_sort | cerebrospinal fluid ctdna testing shows an advantage over plasma ctdna testing in advanced non small cell lung cancer patients with brain metastases |
| topic | non-small cell lung cancer (NSCLC) leptomeningeal metastases (LM) brain parenchyma metastases (BPM) cerebrospinal fluid circulating tumour DNA (ctDNA) next generation sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1322635/full |
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