| ObjectiveTo analyze the clinical characteristics and prognosis of patients with anaplastic lymphoma kinase(ALK)positive lung cancer,and to explore the influence of PD-L1 expression status on clinical characteristics and prognosis of patients with ALK positive lung cancer.To provide reference for diagnosis and treatment of ALK+PD-L1+lung cancer patients.MethodsA total of 378 cases of ALK-positive lung cancer diagnosed by pathology from January 1,2017 to November 30,2021 in the First Affiliated Hospital of Soochow University were retrospectively analyzed.The expression of ALK protein was detected by Ventana immunohistochemical method.Our hospital began to routinely examine PD-L1 immune-related protein after 2019.From January 1,2019 to November 30,2021,a total of 291 ALK-positive lung cancer patients with PD-L1 expression status were tested.The clinical data and pathological characteristics of the patients were analyzed,including gender,age,smoking history,clinical symptoms at initial diagnosis,diagnosis method,pathological sampling,T stage,N stage,M stage,clinical stage,pleural effusion,tumor diameter,location classification,solid or not,ground glass or not,pathological type,Ki-67 proliferation index,PD-L1 expression status,treatment and survival time.SPSS 26.0 software was used to analyze the clinical features and prognosis of ALK-positive lung cancer patients.Results1.Of the 378 ALK-positive lung cancer patients,185(48.9%)were male and 193(51.1%)were female.The overall age of the patients ranged from 23 to 86 years,with an average age of 57 years;284 patients(75.1%)had no history of smoking.Two hundred and eleven patients(55.8%)were asymptomatic and 167 patients(44.2%)had clinical symptoms at the first visit.There were 329 cases(87.0%)of adenocarcinoma,27 cases(7.1%)of squamous cell carcinoma,and 10 cases(2.6%)of small cell lung cancer.There were 236 cases(62.4%)with Ki-67<25%and 142 cases(37.6%)with Ki-67≥25%.The positive rate of Ki-67 proliferation index was 99.2%(375/378),and the mean value was 26.2%.98 patients(25.9%)had distant metastasis,with 32 cases(32.3%)of bone metastasis,followed by 27 cases(27.3%)of brain metastasis.188 cases(49.7%)were in stage Ⅰ,32 cases(8.5%)were in stage Ⅱ,60 cases(15.9%)were in stage Ⅲ,and 98 cases(25.9%)were in stage Ⅳ.There were 314 cases(83.1%)of peripheral lung cancer.The density of 270 cases(71.4%)was solid.Among 341 ALK-positive non-squamous NSCLC patients,54 died,and the 1-,3-,and 5-year OS rates were 92.1%,85.0%,and 84.5%,respectively.Univariate analysis showed that clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,location classification,surgery,pleural effusion,solid or not.ground glass or not.bronchial stenosis/occlusion,and tumor diameter were factors affecting PFS in patients with ALK-positive non-squamous non-small cell lung cancer.Multivariate analysis showed that clinical stage,lymph node invasion and distant metastasis were independent prognostic factors for PFS of ALK-positive non-squamous non-small cell lung cancer patients.Univariate analysis showed that clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,location classification,surgery,pleural effusion,solid or not,ground glass or not,bronchial stenosis/occlusion,and tumor diameter were prognostic factors for OS in patients with ALK-positive non-squamous NSCLC.Multivariate analysis showed that Ki-67,clinical stage,lymph node invasion and distant metastasis were independent prognostic factors for OS of ALK-positive non-squamous non-small cell lung cancer patients.2.Among 341 patients with ALK positive non-squamous non-small cell lung cancer,54 died,and the 1-,3-,and 5-,ear OS rates were 92.1%.85.0%,and 84.5%,respectively.Univariate analysis showed that clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,location classification.surgery,pleural effusion,solid or not,ground glass or not,bronchial stenosis/occlusion,and tumor diameter were factors affecting PFS in patients with ALK-positive non-squamous non-small cell lung cancer.Multivariate analysis showed that clinical stage,lymph node invasion and distant metastasis were independent prognostic factors for PFS of ALK-positive non-squamous non-small cell lung cancer patients.Univariate analysis showed that clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,location classification,surgery,pleural effusion,solid or not,ground glass or not,bronchial stenosis/occlusion,and tumor diameter were prognostic factors for OS in patients with ALK-positive non-squamous NSCLC.Multivariate analysis showed that Ki-67,clinical stage,lymph node invasion and distant metastasis were independent prognostic factors for OS of ALK-positive non-squamous non-small cell lung cancer patients.3.Among the 291 ALK-positive lung cancer patients,174(59.8%)were PD-L1 positive and 117(40.2%)were PD-L1 negative.Among 174 cases of PD-L1 positive lung cancer,118 cases(67.8%)had low expression of PD-L1,and 56 cases(32.2%)had high expression of PD-L1.The positive and strong positive rates of PD-L1 in ALK positive patients were 59.8%and 19.2%,respectively.4.The results of the chi-square test show that There were significant differences in age,gender,clinical symptoms at initial diagnosis,pathological specimen,non-squamous non-small cell lung cancer,Ki-67,T stage,N stage,M stage,clinical stage,tumor diameter,location,pleural effusion,solid or not,and ground glass or not between ALK+PD-L1+and ALK+PD-L1-patients.5.260 cases of ALK-positive non-squamous non-small cell lung cancer tested PD-L1 expression status.Univariate analysis showed that:The clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,location classification,surgery,pleural effusion,solid or not,ground glass or not,bronchial stenosis/occlusion,tumor diameter,and PD-L1 expression status at diagnosis are the factors affecting the PFS of ALK-positive non-squamous non-small cell lung cancer.Multivariate analysis showed that distant metastasis and clinical stage were independent prognostic factors for PFS in ALK-positive non-squamous non-small cell lung cancer patients.Univariate analysis showed that clinical symptoms,Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,surgery,pleural effusion,solid or not,ground glass or not,bronchial stenosis/occlusion,tumor diameter,and PD-L1 expression were prognostic factors for OS of ALK-positive non-squamous NSCLC.Multivariate analysis showed that distant metastasis,clinical stage,Ki-67 proliferation index and PD-L1 expression were independent prognostic factors for OS in patients with ALK-positive non-squamous non-small cell lung cancer.6.Univariate analysis of 150 ALK+PD-L1+non-squamous non-small cell lung cancer patients showed that lymph node invasion,distant metastasis,clinical stage,pleural effusion,solid or not,bronchial stenosis/occlusion were the factors affecting the PFS of ALK+PD-L1+non-squamous non-small cell lung cancer patients.Multivariate analysis showed that clinical stage and distant metastasis were independent prognostic factors for PFS in ALK+PD-L1+non-squamous non-small cell lung cancer patients.Univariate analysis showed that Ki-67 proliferation index,lymph node invasion,distant metastasis,clinical stage,pleural effusion and bronchial stenosis/occlusion were prognostic factors for OS of ALK+PD-L1+non-squamous non-small cell lung cancer patients.Multivariate analysis showed that clinical stage was an independent prognostic factor for OS of ALK+PD-L1+non-squamous non-small cell lung cancer patients.In ALK+PD-L1+lung cancer patients,there was no significant difference in PFS and OS between PD-L1 high expression group and PD-L1 low expression group.7.Kaplan-Meier survival analysis showed that in patients with ALK-positive lung cancer treated by surgery in stage Ⅲ-Ⅳ,PFS and OS of PD-L1+lung cancer patients without targeted therapy were significantly lower than those of PD-L1-patients.The OS and PFS of PD-L1+lung cancer patients receiving targeted therapy were lower than those of PD-L1-patients,but the difference was not statistically significant.In the non-surgical treatment group of stage Ⅲ-Ⅳ,the PFS and OS of patients with targeted therapy were significantly higher than those of patients with chemotherapy.Among the patients with targeted therapy,there was no significant difference in PFS and OS between PD-L1-lung cancer patients and PD-L1-lung cancer patients,which may be related to the small proportion of PD-L1-lung cancer patients(10.3%).8.A total of 7 ALK+PDL1-lung cancer patients had received immunotherapy,of which 5 patients received targeted and immune sequential therapy.Conclusions1.Among ALK-positive lung cancer patients,more patients are PD-L1-positive than negative.The clinical characteristics of ALK+PD-L1+lung cancer patients were mainly male,older age,more clinical symptoms at initial diagnosis,larger tumor diameter,advanced clinical stage,and high expression of Ki-67.2.In patients with ALK-positive non-squamous non-small cell lung cancer,bronchial stenosis/occlusion is an independent prognostic factor for PFS.Bronchial stenosis/occlusion and PD-L1 expression are independent prognostic factors for OS.The PFS and OS of ALK+PD-L1+group were significantly lower than those of ALK+PD-L1-group.3.In patients with stage Ⅲ-Ⅳ ALK-positive non-squamous non-small cell lung cancer who did not receive surgery,OS and PFS of targeted therapy were significantly higher than those of chemotherapy.4.There are individual differences in the efficacy of sequential targeted and immune therapy in ALK+PD-L1+patients,which can provide a basis for clinical treatment of ALK+PD-L1+patients. |
