Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan.
Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan.
Clin Lung Cancer. 2018 Mar;19(2):181-190. doi: 10.1016/j.cllc.2017.10.017. Epub 2017 Oct 28.
The clinical benefit of liquid biopsy for unselected patients at initial diagnosis has thus far been unclear. We aimed to evaluate the utility of liquid biopsy at initial diagnosis, as well as the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) based on liquid biopsy results in clinical practice, using the improved peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method.
We routinely performed liquid biopsy using the improved PNA-LNA PCR clamp method for all patients diagnosed with non-small-cell lung cancer (NSCLC) between June 2015 and October 2016. We retrospectively evaluated the reliability of liquid biopsy based either on clinical stage or between sensitizing EGFR mutation and T790M mutation, and the clinical benefit of EGFR-TKI based on the liquid biopsy results in practice.
A total of 244 patients underwent liquid biopsies, with 168 patients tested at diagnosis and 22 tested for T790M after pretreatment of EGFR-TKI. For detecting a sensitizing EGFR mutation, the sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 100%, 100%, and 93.7% in the group with advanced-stage NSCLC and 0, 100%, not evaluable, and 70.5% in the group with early-stage NSCLC. The positive predictive value and negative predictive value for T790M were 33.3% and 55.6%, respectively. Fourteen patients in the liquid-positive group and 16 patients in the tissue-positive group received EGFR-TKI. The objective response rates of first- and second-generation EGFR-TKI for the liquid-positive and tissue-positive groups were 90.0% and 90.9%, respectively. There was no significant difference in median progression-free survival between the liquid-positive and tissue-positive groups (P = .839).
Patients with early-stage NSCLC should not be candidates for this liquid biopsy method. We recommend tissue biopsy as the preferred initial method of molecular analysis, with the exception of patients who are T790M positive or patients who are unable to tolerate invasive biopsy.
液体活检在初始诊断时对未经选择的患者的临床获益尚不清楚。我们旨在使用改良的肽核酸锁核酸（PNA-LNA）PCR 夹心法评估液体活检在初始诊断时的效用，以及液体活检结果对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）的疗效。
我们于 2015 年 6 月至 2016 年 10 月期间，对所有诊断为非小细胞肺癌（NSCLC）的患者常规使用改良的 PNA-LNA PCR 夹心法进行液体活检。我们回顾性评估了液体活检基于临床分期或基于敏感 EGFR 突变与 T790M 突变之间的可靠性，以及液体活检结果对 EGFR-TKI 治疗的临床获益。
共有 244 例患者接受了液体活检，其中 168 例在诊断时进行了检测，22 例在 EGFR-TKI 预处理后进行了 T790M 检测。在检测敏感 EGFR 突变时，晚期 NSCLC 组的敏感性、特异性、阳性预测值和阴性预测值分别为 72.7%、100%、100%和 93.7%，而早期 NSCLC 组分别为 0、100%、无法评估和 70.5%。T790M 的阳性预测值和阴性预测值分别为 33.3%和 55.6%。液体阳性组中有 14 例患者和组织阳性组中有 16 例患者接受了 EGFR-TKI 治疗。液体阳性组和组织阳性组的第一代和第二代 EGFR-TKI 的客观缓解率分别为 90.0%和 90.9%。液体阳性组和组织阳性组的中位无进展生存期无显著差异（P=0.839）。
早期 NSCLC 患者不应成为该液体活检方法的候选者。我们建议组织活检作为首选的初始分子分析方法，除非患者 T790M 阳性或无法耐受有创性活检。
