浸润性肺腺癌的倍增时间与驱动基因状态的相关性

Correlation between tumor doubling time and driver gene status in invasive lung adenocarcinoma

目的比较伴或不伴基因突变的原发性肺腺癌在体积倍增时间(volume doubling time,VDT)和质量倍增时间(mass doubling time,MDT)间的差异。方法选取2019年1月—2020年12月在同济大学附属上海市肺科医院进行手术治疗且术前至少进行2次胸部非增强CT扫描的患者为研究对象。根据放射科医师手工分割的三维掩模计算VDT和MDT。采用Bland-Altman方法进行观察者内变异性评估。采用Mann-Whitney U检验比较驱动基因有无突变肿瘤的VDT和MDT差异。采用Kruskal-Wallis检验比较不同EGFR突变位点VDT和MDT的差异。结果共计279例患者(男性99例,女性280例),平均年龄(62.15±8.90)岁,共287个结节。根据驱动基因状态分为突变组72例,野生组215例,基因突变发生率为74.9%(215/287)。突变组和野生组MDT在驱动基因状态上的差异有统计学意义(537 d vs 824 d,P=0.004),VDT的差异无统计学意义(767 d vs 593 d)。EGFR阳性腺癌的MDT比EGFR阴性腺癌长,但VDT差异并不显著(VDT,758 d vs 593 d,P=0.382;MDT,824 d vs 537 d,P=0.004)。在生长结节中,驱动基因阳性腺癌的VDT和MDT均比野生型腺癌长(VDT,759 d vs 592 d,P=0.048;MDT,749 d vs 499 d,P<0.001;VDT,768 d vs 593 d,P=0.081,MDT,737 d vs 518 d,P=0.001)。结论在原发性浸润性肺腺癌中,驱动基因阳性(尤其是EGFR阳性)的肿瘤倍增时间更长,且在生长中的结节中更为显著。

Objective To investigate the correlation between tumor doubling time and driven gene status in primary invasive lung adenocarcinoma.Methods Patients with invasive lung adenocarcinoma who underwent curative surgery in Shanghai Pulmonary Hospital from January 2019 to December 2020 and had at least two preoperative non-enhanced chest CT scans were included in this retrospective study.The volume doubling time(VDT)and mass doubling time(VDT)were calculated based on the three-dimensional mask segmented by radiologists manually.Intraobserver variability assessment was conducted with the Bland-Altman method.The VDTs and MDTs of tumors were compared among patients with different driver gene status by utilizing the Mann-Whitney U test.The Kruskal-Wallis test was performed to compare the difference in VDT and MDT among multiple groups.Results A total of 279 lung adenocarcinoma patients(aged 62.15±8.90 years and 99 were males)with 287 nodules were included in the study.The prevalence of genetic mutations was 74.9%(215/287).There was significant difference in MDT between patients with mutant-type and wild-type driven genes(537 d vs 824 d,P=0.004),while there was no significant difference in VDT(593 d vs 767 d,P=0.447).EGFR-positive adenocarcinoma showed longer VDT and MDT than EGFR-negative adenocarcinoma(758 d vs 593 d,P=0.382 and 824 d vs 537 d,P=0.004).In growing nodules,the driver gene-positive adenocarcinoma showed longer VDT and MDT than wild-type adenocarcinoma(volume-growing nodules,759 d vs 592 d,P=0.048 and 749 d vs 499 d,P<0.001;mass-growing nodules,768 d vs 593 d,P=0.081 and 737 d vs 518 d,P=0.001).Conclusion In primary invasive lung adenocarcinoma,driver gene-positive(especially EGFR-positive)tumors have a longer doubling time,which is more significant in growing nodules.