Veccia Antonello, Girlando Salvatore, Dipasquale Mariachiara, Kinspergher Stefania, Barbareschi Mattia, Caffo Orazio
Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
J BUON. 2020 Mar-Apr;25(2):848-854.
The EGFR (Epidermal Growth Factor Receptor) mutations may predict sensitivity and resistance to EGFR-TKIs (Tyrosine Kinases Inhibitors) in metastatic lung adenocarcinoma. The detection of these mutations is usually performed on tumor tissue samples. However, when a biopsy is not feasible or the amount of tissue is limited, circulating tumor DNA (ctDNA) may represent an alternative source for genotyping the tumor.
In the first phase of the study, the liquid biopsy was performed in newly diagnosed metastatic lung adenocarcinoma patients with and without EGFR mutations to evaluate the concordance between EGFR mutational analysis on ctDNA by real time PCR and on tissue. In the second phase it was performed in EGFR positive patients progressing after first or second generation TKIs in order to detect the T790M mutation.
In the first phase, a 100% concordance between EGFR on ctDNA and tissue was revealed, leading to validation of the test. In the second phase, 44.8% of patients showed T790M positive result at liquid biopsy. Considering the re-biopsies performed in 31% of the cases, the overall positivity rate of T790M was 58.6%. Sensitivity and specificity were 76% and 75%, respectively. The median time to development of T790M mutation from the start of first line EGFR TKI was 244 days.
Our experience confirms that liquid biopsy is a valid method to detect sensitizing and resistant EGFR mutations in patients with metastatic lung adenocarcinoma. Nevertheless, in the presence of negative ctDNA analysis, a rebiopsy should be performed whenever possible to confirm this result.
表皮生长因子受体（EGFR）突变可预测转移性肺腺癌对EGFR酪氨酸激酶抑制剂（EGFR-TKIs）的敏感性和耐药性。这些突变的检测通常在肿瘤组织样本上进行。然而，当活检不可行或组织量有限时，循环肿瘤DNA（ctDNA）可能是对肿瘤进行基因分型的另一种来源。
在研究的第一阶段，对新诊断的有或无EGFR突变的转移性肺腺癌患者进行液体活检，以评估通过实时PCR对ctDNA和组织进行EGFR突变分析的一致性。在第二阶段，对在第一代或第二代TKIs治疗后病情进展的EGFR阳性患者进行检测，以检测T790M突变。
在第一阶段，ctDNA和组织中的EGFR之间显示出100%的一致性，从而验证了该检测方法。在第二阶段，44.8%的患者在液体活检中显示T790M阳性结果。考虑到31%的病例进行了再次活检，T790M的总体阳性率为58.6%。敏感性和特异性分别为76%和75%。从一线EGFR TKI开始至T790M突变发生的中位时间为244天。
我们的经验证实，液体活检是检测转移性肺腺癌患者中致敏和耐药EGFR突变的有效方法。然而，在ctDNA分析结果为阴性的情况下，应尽可能进行再次活检以确认该结果。
