Comparison Of Imaging And Clinical Differences Between ALK Fusion And Wild-type Non-small Cell Lung Cancer With Brain Metastasis

Objective:To analyze the difference of brain metastasis(BM)in terms of imaging between anaplastic lymphoma kinase(ALK)gene fusion(ALK+)and ALK/epidermal growth factor receptor(EGFR)wild-type(ALK-/EGFR-)in non-small cell lung cancer(NSCLC).Furthermore,we have preliminarily explored the role of radiotherapy efficacy in the BM.Methods:We retrospectively reviewed 101 NSCLC patients with brain metastasis treated in Shanxi Cancer Hospital from January 2013 to December 2021,the involved patients were divided into ALK+ group(n = 41)and ALK-/EGFR-group(n = 60)according to the status of ALK.The differences of brain MRI and clinical features between the two groups were compared by univariate and multivariate analysis,and nomogram was constructed to predict ALK gene fusion.Among them,56 patients with non-operative treatment had complete imaging and follow-up data before and after treatment.According to receiving radiotherapy or not,they were divided into radiotherapy group and non-radiotherapy group.Kaplan-Meier was used to draw Survival Curve.Log-rank test was used to compare the short-term effect of treatment between the two groups under different gene mutation status.Results:1.Univariate and multivariate analysis showed that ALK-positive was more common in patients with young,non-smoking and time of BM(more than 6 months).MRI examination of brain showed small peritumoral brain edema index(PBEI)and homogeneous enhancement of brain metastases.Age(OR =1.04;95%CI: 1.02-1.06),time of BM(OR =1.50;95%CI: 1.04-2.14),PBEI(OR =1.26;95%CI: 0.97-1.62),smoking status(Smoking index > 400 vs No smoking: OR =1.42;95%CI: 0.99-2.04)and contrast enhancement pattern(OR =1.89;95%CI: 1.28-2.78)were related to ALK gene fusion.Then the nomogram was constructed based on the above variables,and it is found that the prediction efficiency of the model is acceptable(AUC value is 0.844).In the calibration curve,the calibration line is close to the ideal line,and the average absolute error of calibration is 0.033,indicating that the predicted results of the model are in good agreement with the actual observation results.In the DCA curve,there is a high clinical net benefit under the threshold probability of 0.01-0.99.The nomogram showed highly repeatable(the average AUC values are 0.843 and 0.828 respectively in five-fold cross validation).2.Radiotherapy effect analysis showed that in 56 patients with non-operative treatment,radiotherapy only significantly improved the disease control rate(DCR),but did not significantly improve the progression free survival time(PFS)and objective remission rate(ORR)(all P > 0.05).In the subgroup analysis,radiotherapy only significantly improved ORR in ALK+ group,but did not significantly improve PFS and DCR(all P > 0.05).However,in ALK-/EGFR-group,radiotherapy significantly improved PFS,ORR and DCR.Conclusion:There are significant differences in imaging and clinical features between ALK positive and ALK/EGFR negative non-small cell lung cancer brain metastases,which can indicate the status of ALK to some extent and can be used as a reference for patients who cannot be detected by histology;The short-term effect of radiotherapy to brain metastases in ALK+ group is inferior than that in ALK-/EGFR-group.