Seki Yoshitaka, Fujiwara Yutaka, Kohno Takashi, Yoshida Kazushi, Goto Yasushi, Horinouchi Hidehito, Kanda Shintaro, Nokihara Hiroshi, Yamamoto Noboru, Kuwano Kazuyoshi, Ohe Yuichiro
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
ESMO Open. 2018 Feb 8;3(2):e000292. doi: 10.1136/esmoopen-2017-000292. eCollection 2018.
Non-invasive monitoring of epidermal growth factor receptor (EGFR) mutations conferring sensitivity and resistance to tyrosine kinase inhibitors (TKIs) is vital for efficient therapy of lung adenocarcinoma (LADC). Although plasma circulating cell-free tumour DNA (ctDNA) is detectable at an early stage, the size of the tumour does not strongly correlate with concentration of whole cell-free DNA (cfDNA), including normal leucocyte DNA. We sought to examine the clinical features of patients with LADC whose cfDNA examination held clues for analysis of cancer genomics.
Forty-four plasma samples from 37 patients with LADC receiving EGFR-TKI therapy, including 20 who developed resistance, were prospectively subjected to droplet digital PCR-cfDNA analysis to detect EGFR mutations and analysed according to clinical features.
cfDNA samples from 28 (64%) of the 44 samples were positive for TKI-sensitive mutations. Samples from 19 (95%) of the 20 EGFR-TKI-resistant patients were positive for TKI-sensitive mutations. In 24 patients without TKI resistance, 7 (54%) of 13 patients with regional lymph node metastases, 4 (67%) of 6 patients with advanced T stage (T3 or T4) and 8 (57%) of 14 patients with extrathoracic disease progression were also positive for TKI-sensitive mutations. cfDNA analysis from patients with acquired TKI-resistance disease or extrathoracic disease progression correlated with a high detection rate of TKIsensitive mutations (acquired resistance: risk ratio=2.53, 95% CI 1.50 to 4.29; extrathoracic disease progression: risk ratio=5.71, 95% CI 0.84 to 36.74).
cfDNA in patients with EGFR-TKI-resistance or extrathoracic disease progression may be useful for analysis of cancer genomics.
UMIN 000017581.
对赋予酪氨酸激酶抑制剂（TKIs）敏感性和耐药性的表皮生长因子受体（EGFR）突变进行无创监测，对于肺腺癌（LADC）的有效治疗至关重要。尽管血浆循环游离肿瘤DNA（ctDNA）在疾病早期即可检测到，但肿瘤大小与包括正常白细胞DNA在内的全游离DNA（cfDNA）浓度并无强烈关联。我们试图研究cfDNA检测可为癌症基因组学分析提供线索的LADC患者的临床特征。
前瞻性地对37例接受EGFR-TKI治疗的LADC患者的44份血浆样本进行液滴数字PCR-cfDNA分析以检测EGFR突变，并根据临床特征进行分析，其中包括20例出现耐药的患者。
44份样本中的28份（64%）cfDNA样本检测到TKI敏感突变呈阳性。20例EGFR-TKI耐药患者中的19份（95%）样本检测到TKI敏感突变呈阳性。在24例未出现TKI耐药的患者中，13例有区域淋巴结转移的患者中有7例（54%）、6例T分期较晚（T3或T4）的患者中有4例（67%）以及14例有胸外疾病进展的患者中有8例（57%）检测到TKI敏感突变也呈阳性。对获得性TKI耐药疾病或胸外疾病进展患者的cfDNA分析显示，TKI敏感突变的检出率较高（获得性耐药：风险比=2.53，95%可信区间1.50至4.29；胸外疾病进展：风险比=5.71，95%可信区间0.84至36.74）。
EGFR-TKI耐药或胸外疾病进展患者的cfDNA可能有助于癌症基因组学分析。
UMIN 000017581。
