双层探测器光谱CT在EGFR及ALK基因突变型肺腺癌中的应用

Application of Dual-Layer Detector Spectral CT in the EGFR and ALK Gene Mutations of Lung Adenocarcinoma

目的利用双层探测器光谱CT(DLCT)多参数成像研究表皮生长因子受体(EGFR)突变及间变性淋巴瘤激酶(ALK)重排型肺腺癌的临床及DLCT特点,为临床判断肺腺癌基因表达探索无创的预测方法。资料与方法前瞻性收集甘肃省人民医院2020年8月—2022年3月病理确诊的肺腺癌98例,统计其临床参数(性别、年龄、病灶数量、形态、有无纵隔淋巴结转移及EGFR、ALK基因状态)及DLCT参数[动、静脉期光谱曲线斜率(λHUA、λHUV)、动、静脉期标准碘浓度(NICA、NICV)、动、静脉期40 keV单能CT值(CTA 40 keV、CTV 40 keV)、动、静脉期有效原子序数];按EGFR、ALK表达分为EGFR突变组[EGFR(+)]、ALK重排组[ALK(+)]及EGFR/ALK均阴性组[EGFR/ALK(-)];比较各组临床及DLCT参数特点。结果EGFR(+)组和EGFR/ALK(-)组性别差异有统计学意义(χ^(2)=11.010,P<0.05);3组病灶形态差异有统计学意义(χ^(2)=12.858,P<0.05)。EGFR(+)组平均CTV 40 keV大于EGFR/ALK(-)组(t=1.997,P<0.05);ALK(+)组平均NICV小于EGFR/ALK(-)组(t=2.155,P<0.05);EGFR(+)组平均λHUV、NICV、CTV 40 keV均大于ALK(+)组(t=2.613,3.149,3.218,P<0.05)。CTV 40 keV为141.070 Hu时,鉴别EGFR(+)及EGFR/ALK(-)腺癌的敏感度、特异度为62.7%、70.0%,曲线下面积(AUC)为0.634(95%CI 0.516~0.756);NICV为0.287时,鉴别ALK(+)及EGFR/ALK(-)腺癌的敏感度、特异度为76.7%、64.2%,AUC为0.706(95%CI 0.536~0.853);λHUV、NICV、CTV 40 keV分别为1.335、0.320、132.350时,区分EGFR(+)及ALK(+)腺癌的敏感度分别为70.6%、64.7%、72.5%,特异度为76.5%、76.5%、82.4%,AUC为0.734(95%CI 0.606~0.829)、0.751(95%CI 0.610~0.832)、0.773(95%CI 0.649~0.861);Delong检验示CTV 40 keV、λHUV区分EGFR(+)及ALK(+)腺癌的AUC差异有统计学意义(Z=2.327,P<0.05)且CTV 40 keV的AUC达0.773。结论肺腺癌患者的性别、病灶形态及DLCT参数(λHUV、CTV 40 keV、NICV)对腺癌的EGFR及ALK基因表达有一定预测价值,能帮助临床判断腺癌的基因突变状态。

Purpose The clinical and dual-layer detector spectral CT(DLCT)features of epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement of lung adenocarcinoma were studied by DLCT multi-parameter imaging to explore a non-invasive prediction method for clinical diagnosis of lung adenocarcinoma gene expression.Materials and Methods A total of 98 cases of lung adenocarcinoma diagnosed by pathology in Gansu Provincial Hospital were prospectively collected from August 2020 to March 2022.Clinical parameters(gender,age,lesion morphology,number,mediastinal lymph node metastasis,EGFR and ALK mutations status)and DLCT parameters including slope of the spectrum curve of the arteriovenous phase(λHUA,λHUV),the standard iodine concentration of the arteriovenous phase(NICA,NICV),the 40 keV single-energy CT value of the arteriovenous phase(CTA 40 keV,CTV 40 keV),the active atomic number of the arteriovenous phases were collected,respectively.According to the expression of EGFR and ALK,all patients were divided into three groups:EGFR mutant group[EGFR(+)],ALK rearrangement group[ALK(+)],EGFR/ALK both negative group[EGFR/ALK(-)].Clinical and DLCT parameters of each group were analyzed.Results There were statistical difference in gender between the EGFR(+)group and EGFR/ALK(-)group(χ^(2)=11.010,P<0.05).There were statistical differences in lesion morphology among the three groups(χ^(2)=12.858,P<0.05).The value of CTV 40 keV in the EGFR(+)group was significantly higher than that in EGFR/ALK(-)group(t=1.997,P<0.05),and the NICV in the ALK(+)group was significantly lower than that in EGFR/ALK(-)group(t=2.155,P<0.05).TheλHUV,NICV,CTV 40 keV of EGFR(+)group were significantly higher than those of ALK(+)group(t=2.613,3.149,3.218,all P<0.05).The sensitivity and specificity to identify EGFR(+)and EGFR/ALK(-)adenocarcinoma were 62.7%and 70.0%,the area under curve(AUC)was 0.634(95%CI 0.516-0.756)when the CTV 40 keV value was 141.070 Hu.The sensitivity and specificity to identify ALK(+)and EGFR/ALK(-)adenocarcinoma were 76.7%and 64.2%,the AUC was 0.706(95%CI 0.536-0.853)when NICV value was 0.287.The sensitivity to identify EGFR(+)and ALK(+)adenocarcinoma were 70.6%,64.7%,72.5%and the specificity was 76.5%,76.5%,82.4%,respectively,the AUC was 0.734(95%CI 0.606-0.829),0.751(95%CI 0.610-0.832),0.773(95%CI 0.649-0.861)when the values ofλHUV,NICV and CTV 40 keV were 1.335,0.320 and 132.350,respectively.Delong test showed that the AUC of CTV 40 keV andλHUV was statistically different(Z=2.327,P<0.05),and the AUC of CTV 40 keV was 0.773.Conclusion The gender,lesion morphology and DLCT parameters(λHUV,CTV 40 keV,NICV)of lung adenocarcinoma have certain predictive value for EGFR and ALK genetic expression,which can help clinical judgment of lung adenocarcinoma gene mutation pattern.