Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb
{"title":"Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.","authors":"Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb","doi":"10.3233/cbm-230431","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).\r\n\r\nOBJECTIVE\r\nThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.\r\n\r\nMETHODS\r\nWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.\r\n\r\nRESULTS\r\nOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).\r\n\r\nCONCLUSIONS\r\nctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/cbm-230431","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

Abstract

BACKGROUND Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). CONCLUSIONS ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.
循环肿瘤 DNA (ctDNA) 作为 Nivolumab 治疗晚期肝细胞癌疗效的生物标记物。
背景循环肿瘤DNA(ctDNA)是肝细胞癌(HCC)检测、诊断、治疗选择和预后判断的一种很有前景的非侵入性标记物。目的本研究旨在检验ctDNA作为预后和预测工具在接受尼伐单抗治疗的HCC患者中的实用性。方法我们利用市售平台上的综合基因组检测分析了44名HCC患者治疗前的ctDNA。我们利用对数秩检验和单变量 Cox 模型将总生存期(OS)和无进展生存期(PFS)与 ctDNA 表达相关联。除3名患者外,所有患者都至少发现了一种基因改变,TP53是最常见的改变基因(52.3%)。中位OS为17.5个月(95% CI:12.7,NA)。涉及PIK3CA、BRCA1和CCND1扩增的基因突变与较短的OS相关(P分别为0.0001、0.0001和0.01)。中位生存时间为4.01个月(95% CI:3.06,9.33)。涉及KIT和PIK3CA的突变与较短的PFS相关(P分别为0.0001和0.0004),而涉及CTNNB1的突变与较长的PFS相关(P= 0.04)。需要未来的研究加以证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
×
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