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Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling
Cancer Discovery ( IF 28.2 ) Pub Date : 2017-12-01 , DOI: 10.1158/2159-8290.cd-17-0716
Aadel A. Chaudhuri , Jacob J. Chabon , Alexander F. Lovejoy , Aaron M. Newman , Henning Stehr , Tej D. Azad , Michael S. Khodadoust , Mohammad Shahrokh Esfahani , Chih Long Liu , Li Zhou , Florian Scherer , David M. Kurtz , Carmen Say , Justin N. Carter , David J. Merriott , Jonathan C. Dudley , Michael S. Binkley , Leslie Modlin , Sukhmani K. Padda , Michael F. Gensheimer , Robert B. West , Joseph B. Shrager , Joel W. Neal , Heather A. Wakelee , Billy W. Loo , Ash A. Alizadeh , Maximilian Diehn

Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here, we apply cancer personalized profiling by deep sequencing (CAPP-seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I–III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first posttreatment blood sample, indicating reliable identification of MRD. Posttreatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months, and 53% of patients harbored ctDNA mutation profiles associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in patients with lung cancer can be accurately detected using CAPP-seq and may allow personalized adjuvant treatment while disease burden is lowest.

Significance: This study shows that ctDNA analysis can robustly identify posttreatment MRD in patients with localized lung cancer, identifying residual/recurrent disease earlier than standard-of-care radiologic imaging, and thus could facilitate personalized adjuvant treatment at early time points when disease burden is lowest. Cancer Discov; 7(12); 1394–403. ©2017 AACR.

See related commentary by Comino-Mendez and Turner, p. 1368.

This article is highlighted in the In This Issue feature, p. 1355



中文翻译:

循环肿瘤DNA谱分析在局部肺癌分子残留病中的早期发现

在局部肺癌治疗后识别分子残留疾病(MRD)可以促进辅助疗法的早期干预和个性化。在这里,我们通过深度测序(CAPP-seq)循环肿瘤DNA(ctDNA)分析对癌症样本进行了个性化分析,这些样本来自40例经过I-III期肺癌根治性治疗的患者和54名健康成年人的255个样品。在94%的可评估复发患者中,在治疗后的第一个血液样本中可检测到ctDNA,这表明可以可靠地鉴定MRD。治疗后ctDNA检测在72%的患者放射学进展之前中位数为5.2个月,并且53%的患者具有ctDNA突变特征与对酪氨酸激酶抑制剂或免疫检查点封锁的良好反应相关。总的来说,

意义:这项研究表明,ctDNA分析可以强有力地识别出局限性肺癌患者的治疗后MRD,比照护标准放射影像学更早地识别残留/复发性疾病,因此可以在疾病负担加重的早期提供便利的个性化辅助治疗最低。巨蟹座Discov; 7(12);1394–403。©2017 AACR。

参见Comino-Mendez和Turner的相关评论,第10页。1368年

本文在本期功能中突出显示。1355

更新日期:2017-12-05
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