Jia-Xin Lin PhD , Kai Yin PhD , Li-Xu Yan PhD , Mei-Mei Zheng PhD , Yang-Si Li PhD , Shi-Ling Zhang MS , Kang-Hui Zeng MS , Hong-Hong Yan MS , Hai-Yan Tu PhD , Zhi-Hong Chen MS , Xu-Chao Zhang PhD , Qing Zhou PhD , Jin-Ji Yang PhD , Ben-Yuan Jiang PhD , Qing-Ling Zhang PhD , Yi-Long Wu MD
{"title":"结合细胞学和脑脊液中的ctDNA,揭示肺腺癌多脑膜转移患者的小细胞肺癌转化过程","authors":"Jia-Xin Lin PhD , Kai Yin PhD , Li-Xu Yan PhD , Mei-Mei Zheng PhD , Yang-Si Li PhD , Shi-Ling Zhang MS , Kang-Hui Zeng MS , Hong-Hong Yan MS , Hai-Yan Tu PhD , Zhi-Hong Chen MS , Xu-Chao Zhang PhD , Qing Zhou PhD , Jin-Ji Yang PhD , Ben-Yuan Jiang PhD , Qing-Ling Zhang PhD , Yi-Long Wu MD","doi":"10.1016/j.jtocrr.2024.100704","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in <em>EGFR</em>-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce.</p></div><div><h3>Methods</h3><p>We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing.</p></div><div><h3>Results</h3><p>Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the <em>EGFR</em> mutation, including four patients with <em>EGFR exon 19 deletion</em> and three patients with <em>EGFR</em> <em>exon</em> <em>21 L858R</em> mutation. Another patient harbored <em>ERBB2</em> insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that <em>TP53</em> and <em>RB1</em> mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0–17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2–29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0–5.9 mo).</p></div><div><h3>Conclusions</h3><p>SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000742/pdfft?md5=870ec4f4f2918aac97890cf20e833f5f&pid=1-s2.0-S2666364324000742-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma\",\"authors\":\"Jia-Xin Lin PhD , Kai Yin PhD , Li-Xu Yan PhD , Mei-Mei Zheng PhD , Yang-Si Li PhD , Shi-Ling Zhang MS , Kang-Hui Zeng MS , Hong-Hong Yan MS , Hai-Yan Tu PhD , Zhi-Hong Chen MS , Xu-Chao Zhang PhD , Qing Zhou PhD , Jin-Ji Yang PhD , Ben-Yuan Jiang PhD , Qing-Ling Zhang PhD , Yi-Long Wu MD\",\"doi\":\"10.1016/j.jtocrr.2024.100704\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in <em>EGFR</em>-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce.</p></div><div><h3>Methods</h3><p>We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing.</p></div><div><h3>Results</h3><p>Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the <em>EGFR</em> mutation, including four patients with <em>EGFR exon 19 deletion</em> and three patients with <em>EGFR</em> <em>exon</em> <em>21 L858R</em> mutation. Another patient harbored <em>ERBB2</em> insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that <em>TP53</em> and <em>RB1</em> mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0–17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2–29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0–5.9 mo).</p></div><div><h3>Conclusions</h3><p>SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.</p></div>\",\"PeriodicalId\":17675,\"journal\":{\"name\":\"JTO Clinical and Research Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2666364324000742/pdfft?md5=870ec4f4f2918aac97890cf20e833f5f&pid=1-s2.0-S2666364324000742-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JTO Clinical and Research Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666364324000742\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364324000742","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma
Introduction
Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce.
Methods
We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing.
Results
Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFRexon21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0–17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2–29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0–5.9 mo).
Conclusions
SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.