Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Universidad Autónoma de Barcelona (UAB), Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Clin Lung Cancer. 2018 Sep;19(5):387-394.e2. doi: 10.1016/j.cllc.2018.03.015. Epub 2018 Mar 23.
The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity.
Consecutive patients diagnosed with EGFR-mutant lung adenocarcinoma in tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease. EGFR mutations in plasma were quantified using BEAMing (beads, emulsions, amplification, and magnetics) or digital PCR and were correlated with mutations in tumor and with radiologic response and progression.
Two hundred twenty-one plasma samples from 33 patients were analyzed. EGFR mutations in plasma were detected in 83% of all patients and 100% of those with extrathoracic metastases. The dynamics of the EGFR mutation load predicted response in 93% and progression in 89% of cases well in advance of radiologic evaluation. Progression-free survival for patients in whom ctDNA was not detected in plasma during treatment was significantly longer than for those in whom ctDNA remained detectable (295 vs. 55 days; hazard ratio, 17.1; P < .001).
The detection of EGFR mutations in ctDNA showed good correlation with that in tumor biopsy and predicted tumor response and progression in most patients. The liquid biopsy for ctDNA-based assessment of EGFR mutations is a reliable technique for diagnosis and follow-up in patients with EGFR-mutant lung adenocarcinoma in routine clinical practice.
表皮生长因子受体（EGFR）突变的评估对于肺腺癌患者的治疗至关重要。与肿瘤相比，基于循环肿瘤 DNA（ctDNA）的评估具有优势，因为它是一种能够捕获肿瘤异质性的微创方法。
本研究纳入了经肿瘤活检诊断为 EGFR 突变型肺腺癌的连续患者。在疾病过程中的不同时间点获取血浆样本。使用 BEAMing（珠子、乳液、扩增和磁性）或数字 PCR 定量检测血浆中的 EGFR 突变，并将其与肿瘤中的突变以及与放射学反应和进展进行相关性分析。
分析了 33 名患者的 221 个血浆样本。所有患者中有 83%和有远处转移的患者中有 100%可检测到血浆中的 EGFR 突变。EGFR 突变负荷的动态变化可提前准确预测 93%的患者对治疗的反应和 89%的进展情况。在治疗期间血浆中未检测到 ctDNA 的患者无进展生存期明显长于仍能检测到 ctDNA 的患者（295 天 vs. 55 天；危险比，17.1；P <.001）。
ctDNA 中 EGFR 突变的检测与肿瘤活检具有良好的相关性，并可预测大多数患者的肿瘤反应和进展。基于液体活检的 ctDNA 检测 EGFR 突变是常规临床实践中诊断和随访 EGFR 突变型肺腺癌患者的可靠技术。
