Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling.
Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling.
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DOI：
10.1158/2159-8290.cd-17-0716
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发表时间：
2017-12
期刊：
影响因子：
28.2
通讯作者：
Diehn M
中科院分区：
文献类型：
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作者：
Chaudhuri AA;Chabon JJ;Lovejoy AF;Newman AM;Stehr H;Azad TD;Khodadoust MS;Esfahani MS;Liu CL;Zhou L;Scherer F;Kurtz DM;Say C;Carter JN;Merriott DJ;Dudley JC;Binkley MS;Modlin L;Padda SK;Gensheimer MF;West RB;Shrager JB;Neal JW;Wakelee HA;Loo BW Jr;Alizadeh AA;Diehn M
识别局部肺癌治疗后的分子残留病（MRD）有助于早期干预和辅助治疗的个性化。在这里，我们通过深度测序（CAPP-seq）循环肿瘤DNA（ctDNA）分析对来自40名I-III期肺癌患者和54名健康成人的255个样本进行了癌症个性化分析。在94%的可评估复发患者中，在第一个治疗后血液样本中可检测到ctDNA，表明MRD的可靠鉴定。72%的患者治疗后ctDNA检测先于放射学进展，中位时间为5.2个月，53%的患者携带与酪氨酸激酶抑制剂或免疫检查点阻断剂的良好反应相关的ctDNA突变谱。总的来说，这些结果表明，使用CAPP-seq可以准确检测肺癌患者的ctDNA MRD，并且可以在疾病负担最低的情况下进行个性化辅助治疗。
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 profi ling 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 fi rst posttreatment blood sample, indicating reliable identifi cation 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 profi les 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.