Overall survival with circulating tumor DNA-guided therapy in advanced non-small cell lung cancer.

医学 肺癌 肿瘤科 内科学 前瞻性队列研究 靶向治疗 癌症 生殖系 种系突变 突变 基因 生物化学 化学
作者
Justin Jee,Emily S. Lebow,Yonina R. Murciano‐Goroff,Gowtham Jayakumaran,Ronglai Shen,A. Rose Brannon,Ryma Benayed,Azadeh Namakydoust,Michael Offin,Paul K. Paik,Helena A. Yu,Mark T.A. Donoghue,Ahmet Zehir,Alexander Drilon,David B. Solit,David R. Jones,Charles M. Rudin,Michael F. Berger,James M. Isbell,Bob T. Li
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:39 (15_suppl): 9009-9009 被引量:7
标识
DOI:10.1200/jco.2021.39.15_suppl.9009
摘要

9009 Background: The effectiveness of circulating tumor DNA (ctDNA) at matching patients to life prolonging therapy has been studied mostly in small cohorts with limited follow up. The prognostic value of ctDNA alterations, particularly those absent on tissue, is also unclear. To address these questions, we studied survival outcomes in a prospective cohort of patients (N = 1002) with non-small cell lung cancer (NSCLC). Methods: Adults with metastatic or recurrent NSCLC were eligible if they had no known driver mutation or a known driver with progression following targeted therapy. Patients were enrolled at Memorial Sloan Kettering Cancer Center (New York, NY) starting October 21, 2016; analysis here is from a snapshot November 1, 2020. All patients had ctDNA sequenced via the Resolution ctDx Lung platform. To reduce inclusion of incidental germline mutations, we excluded non-functionally significant mutations with an allele frequency 35-65% that were present in gnomAD. Patients could also receive, at their provider’s discretion, tissue sequencing with MSK-IMPACT, which filters germline and clonal hematopoietic (CH) mutations with matched white blood cell sequencing. We performed survival analyses using Cox proportional hazards models from time of diagnosis of advanced disease to death, left truncating at time of study entry. Results: Of 1002 patients, 348 (35%) were treated with targeted therapy; in 181 of these (52%) the targetable alteration was detected in ctDNA. Patients treated with targeted therapy had prolonged survival whether matched by tissue-based methods (HR 0.39, 95%CI 0.30-0.51) or ctDNA (HR 0.47, 95%CI 0.37-0.61). These benefits persisted across multiple subgroups. ctDNA alterations themselves were associated with worse survival (HR 2.2, 95%CI 1.8-2.8), in a manner that scaled with allele fraction and burden. Of 401 patients with time-matched tissue sampling, 62 (15%) had ctDNA alterations that were absent on IMPACT (“unique” ctDNA alterations). Three such patients had unique ctDNA EGFR T790M mutations leading to changes in therapy. However, unique ctDNA alterations were generally associated with worse survival than no ctDNA alterations (HR 2.5, 95%CI 1.7-3.7) and even tissue-matched ctDNA alterations (HR 1.7, 95%CI 1.1-2.4). Of 98 unique ctDNA mutations, 48 (49%) were detectable in tissue at subthreshold levels, 12 (12%) were filtered by IMPACT as CH or germline, and 38 mutations (39%) were absent even at subthreshold levels. ctDNA alteration burden correlated with radiographic disease extent. In multivariate models with radiographic disease extent and other clinical variables, ctDNA alterations were the strongest independent predictor of worse survival. Conclusions: Our results show that ctDNA may match patients to life-prolonging targeted therapy and have prognostic importance. ctDNA may provide data about a patient’s cancer missed by spatially restricted tissue sequencing. Clinical trial information: NCT01775072.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
maying0318发布了新的文献求助10
1秒前
宣以晴完成签到,获得积分10
1秒前
Nnn完成签到,获得积分10
2秒前
baby完成签到,获得积分10
5秒前
123完成签到,获得积分10
5秒前
6秒前
学术牛马完成签到,获得积分10
6秒前
sl发布了新的文献求助10
8秒前
完美的鹤完成签到,获得积分10
9秒前
hky完成签到,获得积分10
10秒前
TTTHANKS完成签到 ,获得积分10
11秒前
WW完成签到,获得积分10
11秒前
LL完成签到,获得积分10
12秒前
量子星尘发布了新的文献求助10
12秒前
小马的可爱老婆2完成签到,获得积分10
12秒前
缥缈纲完成签到,获得积分10
13秒前
TY完成签到 ,获得积分10
13秒前
迷路的小蚂蚁完成签到,获得积分10
14秒前
哈儿的跟班完成签到,获得积分10
14秒前
醉熏的鑫完成签到,获得积分20
15秒前
远_09完成签到 ,获得积分10
16秒前
网站技术人员完成签到,获得积分10
17秒前
eazin完成签到 ,获得积分10
18秒前
山野桃饼完成签到,获得积分10
18秒前
无私代芹完成签到,获得积分10
19秒前
画风湖湘卷完成签到,获得积分10
19秒前
段一帆完成签到,获得积分10
20秒前
结实的老虎完成签到,获得积分10
20秒前
20秒前
邓希静完成签到,获得积分10
21秒前
24秒前
25秒前
25秒前
27秒前
是冬天完成签到,获得积分10
28秒前
mengwensi完成签到,获得积分10
28秒前
单纯血茗发布了新的文献求助10
28秒前
胡大嘴先生完成签到,获得积分10
28秒前
林钟望完成签到,获得积分10
28秒前
碧蓝碧凡发布了新的文献求助10
29秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038426
求助须知:如何正确求助?哪些是违规求助? 3576119
关于积分的说明 11374556
捐赠科研通 3305834
什么是DOI,文献DOI怎么找? 1819339
邀请新用户注册赠送积分活动 892678
科研通“疑难数据库(出版商)”最低求助积分说明 815029