Gieszer Balazs, Megyesfalvi Zsolt, Dulai Viktoria, Papay Judit, Kovalszky Ilona, Timar Jozsef, Fillinger Janos, Harko Tunde, Pipek Orsolya, Teglasi Vanda, Regos Eszter, Papp Gergo, Szallasi Zoltan, Laszlo Viktoria, Renyi-Vamos Ferenc, Galffy Gabriella, Bodor Csaba, Dome Balazs, Moldvay Judit
Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
National Koranyi Institute of Pulmonology, Budapest, Hungary.
Transl Lung Cancer Res. 2021 Feb;10(2):662-674. doi: 10.21037/tlcr-20-814.
Although lung adenocarcinoma (LADC) with sensitizing mutations of the epidermal growth factor receptor () is highly sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), in most cases disease progression inevitably occurs. Our aim was to investigate the predictive and prognostic significance of adjusted tumoral variant allele frequency (EGFR-aVAF) in the above setting.
Eighty-nine Caucasian advanced-stage LADC patients with known exon-specific mutations undergoing EGFR-TKI treatment were included. The correlations of EGFR-aVAF with clinicopathological variables including progression-free and overall survival (PFS and OS, respectively) were retrospectively analyzed.
Of 89 -mutant LADC patients, 46 (51.7%) had exon 19 deletion, while 41 (46.1%) and 2 (2.2%) patients had exon 21- and exon 18-point mutations, respectively. Tumoral EGFR-aVAF was significantly higher in patients harboring exon 19 mutations than in those with exon 21-mutant tumors (P<0.001). Notably, patients with exon 19 mutant tumors demonstrated significantly improved PFS (P=0.003) and OS (P=0.02) compared to patients with exon 21 mutations. Irrespective of specific exon mutations, a statistically significant positive linear correlation was found between EGFR-aVAF of tumoral tissue and PFS (r=0.319; P=0.002). High (≥70%) EGFR-aVAF was an independent predictor of longer PFS [ low (<70%) EGFR-aVAF; median PFSs were 52 26 weeks, respectively; P<0.001]. Additionally, patients with high EGFR-aVAF also had significantly improved OS than those with low EGFR-aVAF (P=0.011).
Our study suggests that high (≥70%) EGFR-aVAF of tumoral tissue predicts benefit from EGFR-TKI treatment in advanced LADC and, moreover, that exon 19 mutation is associated with high EGFR-aVAF and improved survival outcomes.
尽管具有表皮生长因子受体（EGFR）敏感突变的肺腺癌（LADC）对EGFR酪氨酸激酶抑制剂（EGFR-TKIs）高度敏感，但在大多数情况下疾病进展仍不可避免。我们的目的是研究在上述情况下调整后的肿瘤EGFR变异等位基因频率（EGFR-aVAF）的预测和预后意义。
纳入89例接受EGFR-TKI治疗且已知外显子特异性EGFR突变的白种人晚期LADC患者。回顾性分析EGFR-aVAF与包括无进展生存期和总生存期（分别为PFS和OS）在内的临床病理变量之间的相关性。
在89例EGFR突变的LADC患者中，46例（51.7%）发生外显子19缺失，而41例（46.1%）和2例（2.2%）患者分别发生外显子21和外显子18点突变。携带EGFR外显子19突变的患者肿瘤EGFR-aVAF显著高于外显子21突变肿瘤患者（P<0.001）。值得注意的是，与外显子21突变患者相比，外显子19突变肿瘤患者的PFS（P=0.003）和OS（P=0.02）显著改善。无论具体的外显子突变如何，肿瘤组织的EGFR-aVAF与PFS之间均存在统计学上显著的正线性相关性（r=0.319；P=0.002）。高（≥70%）EGFR-aVAF是PFS延长的独立预测因素[低（<70%）EGFR-aVAF；中位PFS分别为52周和26周；P<0.001]。此外，高EGFR-aVAF患者的OS也显著优于低EGFR-aVAF患者（P=0.011）。
我们的研究表明，肿瘤组织中高（≥70%）EGFR-aVAF预示晚期LADC患者可从EGFR-TKI治疗中获益，此外，外显子19突变与高EGFR-aVAF及改善的生存结果相关。
