厚壁空洞预示着接受一线 EGFR-TKIs 治疗的肺腺癌患者无进展生存期更差。
Thick-wall cavity predicts worse progression-free survival in lung adenocarcinoma treated with first-line EGFR-TKIs.
机构信息
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No 507 Zhengmin Road, Yangpu District, Shanghai, China.
Department of Intensive Care Unit, Shanghai Jingan District Shibei Hospital, Shanghai, China.
出版信息
BMC Cancer. 2018 Oct 23;18(1):1033. doi: 10.1186/s12885-018-4938-9.
BACKGROUND
Cavity occurs in 5.7 to 14.9% of patients with lung adenocarcinoma (ADC). However, the impact of cavity on the therapeutic response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in ADC patients with EGFR mutations remains unclear. The aim of the present retrospective study was to elucidate the incidence and detailed characteristics of EGFR-mutant cavitary ADC and investigate the efficacy of EGFR-TKI treatment in this subgroup.
METHODS
Two hundred seventy-six consecutive patients with advanced EGFR-mutant lung ADC treated with first-line EGFR-TKIs were enrolled. Cavitation and the thickness of cavity wall were assessed based on high-resolution computed tomography scans. Progression-free survival (PFS) was analyzed by the Kaplan-Meier plots and the log-rank test was used to calculate the significance between groups.
RESULTS
Cavity occurred in 5.4% (15/276) of patients with EGFR-mutant lung ADC and was more prevalent among male patients (66.7% vs. 33.3%, P = 0.008). Of the 15 EGFR-mutant cavitary ADC, 9 patients had exon 19 deletion (19DEL) and 6 harbored L858R mutation, 9 patients had thick-wall cavity while 6 had thin-wall cavity. Cavity had an adverse impact on the PFS of EGFR-mutant ADC treated with first-line EGFR-TKIs (noncavity versus cavity, 11.0 versus 6.5 months, hazard ratio [HR]: 0.33, 95% confidence interval [CI], 0.15-0.73, P = 0.003). The impaired effect was only observed in patients with L858R mutation (11.0 vs. 4.2 months, HR: 0.05, 95%CI, 0.01-0.27, P = 0.0003) but not in those with 19DEL (10.4 versus 9.7 months, HR: 0.73, 95%CI, 0.30-1.75, P = 0.483). All six L858R-mutant cavitary ADC patients had thick-wall cavity while thick-wall cavity was only identified in one thirds (3/9) of patients with 19DEL. Further analyses showed that patients with thick-wall cavity had worse PFS (6.0 versus 11.0 months, P = 0.013). Multivariate analysis identified cavity as an independent predictive factor for PFS (HR: 0.49, 95% CI, 0.26-0.90, P = 0.022).
CONCLUSION
Cavitary ADC was associated with a worse PFS of first-line EGFR-TKI therapy, mainly in those with L858R mutation. Thick-wall cavity formation may be the main cause that contribute to the worse PFS.
背景
肺腺癌（ADC）患者中有 5.7%至 14.9%存在空洞。然而，空洞对 EGFR 突变的 ADC 患者接受表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗的疗效影响尚不清楚。本回顾性研究旨在阐明 EGFR 突变的有空洞的 ADC 的发生率和详细特征，并研究该亚组中 EGFR-TKI 治疗的疗效。
方法
纳入 276 例接受一线 EGFR-TKIs 治疗的晚期 EGFR 突变型肺 ADC 患者。根据高分辨率 CT 扫描评估空洞和空洞壁的厚度。通过 Kaplan-Meier 图分析无进展生存期（PFS），并使用对数秩检验计算组间差异的显著性。
结果
5.4%（15/276）的 EGFR 突变型肺 ADC 患者存在空洞，且男性患者更为常见（66.7%比 33.3%，P=0.008）。在 15 例有空洞的 EGFR 突变型 ADC 中，9 例存在外显子 19 缺失（19DEL），6 例存在 L858R 突变，9 例存在厚壁空洞，6 例存在薄壁空洞。空洞对接受一线 EGFR-TKIs 治疗的 EGFR 突变型 ADC 的 PFS 有不良影响（无空洞与有空洞，11.0 个月比 6.5 个月，风险比[HR]：0.33，95%置信区间[CI]：0.15-0.73，P=0.003）。这种受损的影响仅见于 L858R 突变患者（11.0 个月比 4.2 个月，HR：0.05，95%CI：0.01-0.27，P=0.0003），而在 19DEL 患者中则无（10.4 个月比 9.7 个月，HR：0.73，95%CI：0.30-1.75，P=0.483）。所有 6 例 L858R 突变的有空洞的 ADC 患者均存在厚壁空洞，而 19DEL 患者中仅三分之一（3/9）存在厚壁空洞。进一步分析表明，厚壁空洞患者的 PFS 更差（6.0 个月比 11.0 个月，P=0.013）。多变量分析表明，空洞是 PFS 的独立预测因素（HR：0.49，95%CI：0.26-0.90，P=0.022）。
结论
有空洞的 ADC 与一线 EGFR-TKI 治疗的 PFS 更差相关，主要见于 L858R 突变患者。厚壁空洞的形成可能是导致 PFS 更差的主要原因。
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