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

IF 3 Q2 ONCOLOGY
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 ,&nbsp;Kai Yin PhD ,&nbsp;Li-Xu Yan PhD ,&nbsp;Mei-Mei Zheng PhD ,&nbsp;Yang-Si Li PhD ,&nbsp;Shi-Ling Zhang MS ,&nbsp;Kang-Hui Zeng MS ,&nbsp;Hong-Hong Yan MS ,&nbsp;Hai-Yan Tu PhD ,&nbsp;Zhi-Hong Chen MS ,&nbsp;Xu-Chao Zhang PhD ,&nbsp;Qing Zhou PhD ,&nbsp;Jin-Ji Yang PhD ,&nbsp;Ben-Yuan Jiang PhD ,&nbsp;Qing-Ling Zhang PhD ,&nbsp;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":"5 9","pages":"Article 100704"},"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 ,&nbsp;Kai Yin PhD ,&nbsp;Li-Xu Yan PhD ,&nbsp;Mei-Mei Zheng PhD ,&nbsp;Yang-Si Li PhD ,&nbsp;Shi-Ling Zhang MS ,&nbsp;Kang-Hui Zeng MS ,&nbsp;Hong-Hong Yan MS ,&nbsp;Hai-Yan Tu PhD ,&nbsp;Zhi-Hong Chen MS ,&nbsp;Xu-Chao Zhang PhD ,&nbsp;Qing Zhou PhD ,&nbsp;Jin-Ji Yang PhD ,&nbsp;Ben-Yuan Jiang PhD ,&nbsp;Qing-Ling Zhang PhD ,&nbsp;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\":\"5 9\",\"pages\":\"Article 100704\"},\"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}
引用次数: 0

摘要

导言向SCLC转化是表皮生长因子受体(EGFR)突变的肺腺癌(LUAD)对酪氨酸激酶抑制剂的一种耐药机制。方法 我们回顾性地收集了237例因出现脑脊液转移(LM)而接受腰椎穿刺的NSCLC患者。所有脑脊液(CSF)中的 SCLC 转移均由两位经验丰富的病理学家通过细胞学评估确认。结果111例患者(237例中有111例,占46.8%)的CSF样本中发现了肿瘤细胞,8例(111例中有8例,占7.2%)被确定为CSF中有SCLC细胞。七名患者携带表皮生长因子受体突变,其中四名患者的表皮生长因子受体外显子19缺失,三名患者的表皮生长因子受体外显子21 L858R突变。另一名患者携带 ERBB2 插入基因。其中七名患者对靶向治疗耐药。CSF ctDNA分析显示,TP53和RB1突变很常见。从诊断为晚期NSCLC到CSF中发现SCLC转化的中位时间为9.7个月(95%置信区间[CI]:4.0-17.5个月)。转移性 NSCLC 初次诊断后的中位总生存期为 15.3 个月(95% 置信区间:1.2-29.4 个月)。在CSF中检测到SCLC转化后的中位总生存期为5.0个月(95% CI:4.0-5.9个月)。CSF中的SCLC转化可为酪氨酸激酶抑制剂治疗进展期LM的LUAD患者的耐药机制提供信息,而LM的耐药机制与患者的生存率较低有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 EGFR exon 21 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
4.20
自引率
0.00%
发文量
145
审稿时长
19 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信