Correlations Between Ultrasonographic Characteristics And Pathological Types/EGFR Mutation Status Of Non-Small Cell Lung Cancer

Objective: To explore the correlations between ultrasonographic characteristics and pathological types / epidermal growth factor receptor(EGFR)mutation status of non-small cell lung cancer(NSCLC).Also,to evaluate the feasibility of ultrasound imaging findings combined with clinical features as non-invasive predictors for Ki-67 expression level of NSCLC.Methods: A total of 297 patients with NSCLC confirmed by histopathology were included in the study cohort.Two-dimensional ultrasound(2D-US)findings(e.g.,location,shape,maximum diameter,echo,air bronchogram,necrosis,etc.),contrastenhanced ultrasound(CEUS)quantitative parameter(e.g.,time to enhancement,time to peak,time to wash-out,etc.)and qualitative features(e.g.,pattern of enhancement,distribution of vessels in the lesion,extent of enhancement,homogeneity of enhancement,etc.)were observed and recorded.Subsequently,the forementioned ultrasonographic manifestations of different pathological types(adenocarcinoma,squamous cell carcinoma and other NSCLCs)of NSCLC were compared and analyzed.According to the different EGFR mutation status,the cases were divided into EGFR wild group and the EGFR mutation group.And the differences of the ultrasonographic findings were investigate in the two groups.Moreover,a prediction model of Ki-67 expression level in non-small cell lung cancer was constructed on the basis of clinical and ultrasonographic characteristics.Results: 2D-US was highly sensitive to detect NSCLC.The maximum diameter of squamous cell carcinoma and other NSCLCs was generally larger than adenocarcinoma(P < 0.05).Nevertheless,it is still very difficult to make a differential diagnosis of pathological types of NSCLC using 2D-US.Further analysis of relevant CEUS parameters found that both the pulmonary artery and bronchial artery could contribute to the blood supply of NSCLC,while the latter maybe the predominant one.With respect to morphology of enhancement,the early homogenous enhancement and tree-like vessels were more likely to occur in adenocarcinoma,but whereas the chaotic angiogenesis appeared more often in squamous cell carcinoma and other NSCLCs with a late,heterogenous enhancement(all P < 0.05).There were 102 patients whose EGFR mutation status was known.Among them,8 cases of squamous cell carcinoma were excluded for all with EGFR wild type.The remaining 94 cases of adenocarcinoma with EGFR gene testing were divided into wild group(n = 72)and mutant group(n = 22)according to its mutation status.Comparing with the wild group,air bronchogram,pleural indentation and multiple lesions were more often observed on 2D-US in the mutant group(all P < 0.05).In terms of CEUS morphology,adenocarcinoma with EGFR-mutant was more common with homogeneous enhancement,while EGFR wild one was dominated by heterogeneous enhancement(P < 0.05).Further investigation of different mutation sites found there was no statistical difference(all P > 0.05).Finally,the tumors with high expression of Ki-67 were mainly ellipsoid or irregular with rare air bronchogram on 2D-US(all P < 0.05).The CEUS quantitative parameters showed similar results as expected,that is,with the increase of Ki-67 expression,the time to enhancement also prolonged indicating a bronchial arterial blood supply(P < 0.05).Correspondingly,the probability of necrosis in the tumor increased(P < 0.05).In the non-invasive prediction model of Ki-67 expression constructed on clinical and ultrasonographic characteristics,the overall prediction accuracy was stable(70.3%),and it had a good ability to explain the overall variation(the highest pseudo-R square value was 0.327).Conclusion: As a potential imaging tool,CEUS has certain value in the differential diagnosis of different pathological types of NSCLC.It can predict EGFR gene mutation status and Ki-67 expression level in a non-invasive way,and provides auxiliary information for decision-making of clinical treatment plan and prediction of patient prognosis.