Analyses Of Prognostic Factors And Impacts Of Metformin In Type 2 Diabetes Mellitus In Non-small Cell Lung Cancer With Brain Metastases

Objective: To investigate the clinical characteristics and prognosis-related factors of patients in non-small cell lung cancer with brain metastases;and to probe the impact of type 2 diabetes mellitus on survival in patients in non-small cell lung cancer with brain metastases and to explore the relationship between the use of oral medicines such as metformin in patients in duration of DM and prognosis of patients with brain metastases from non-small cell lung cancer survival.Methods: We retrospectively reviewed 463 patients,who were from the department of brain tumor,radiation therapy,pulmonary medicine in Tianjin university cancer institute & hospital,who were diagnosed as non-small cell lung cancer with brain metastases from October 2010 to May 2016.Clinical materials included: gender,age,smoking history,weight lose within three months,lymph node staging,DM history,bone,kidney,adrenal glands metastases,chemotherapy,radiotherapy,surgical therapy,karnofsky score,,metformin oral history.Diabetes group included wholly 85 cases,normal glucose tolerance group included 378 cases.The data were statistically analyzed using SPSS 22.0 software..The measurement data was expressed as the number of cases,or percentages.Use multivariate Cox proportional hazard regression model to make analysis of overall survival(overall survival,OS)and progression free survival(progression free survival,PFS);using Kaplan-Meier survival curves were compared between OS and PFS;the clinical features of the chi square test of diabetic group and normal glucose tolerance group were analyzed with statistical significance.The definition of P was less than 0.05 difference.Result: This study included 463 cases,242 cases were male(52.3%),221 cases were female(47.7%);the median age of patients was 57 years old M(52 years old,64 years old);there were 103 cases of lymph node stage N0(22.2%),30 cases of stage N1(6.5%),146 cases of stage N2(31.5%),and 184 cases of stag N3(39.4% cases);there were 137 patients treated with first-line or second-line chemotherapy trentment(29.6%),249 patients treated with underwent brain radiotherapy(53.8%),119 patients treated with targeted therapy(25.7%).In 463 cases of patients,there were a total of 13 cases treated with pulmonary lesions surgery(2.8%),and 44 patients underwent brain lesions(9.5%),3 patients underwent both of lung and brain surgery(0.7%),a total of 60 cases(13.0%)had a history of surgical operation.Karnofsky score(KPS)of 164 cases ranged from 10 to 70(35.7%),299 cases got 80 to 100 points(64.6%).There were a total of 85 patients in Diabetes mellitus with brain metastases fromnon-small cell lung cancer(18.4%),and a total of 378 patients in normal glucose tolerance group with brain metastases from non-small cell lung cancer(81.6%);diabetes mellitus patients with brain metastases from non-small cell lung cancer who used metformin in the duration,were a total of 44 cases(9.5%),41 patients in the course of diabetes unused double guanidine kind of medicines;DM patients with NSCLC had a history of metformin on the proportion of 44/85 cases(51.8%);a total of 419 patients with brain metastases from non-small cell lung cancer(90.5%)were with no history of metformin taking.There were a total of 85 patients before the diagnosis of BM in patients with diabetes,among them,44 cases were treated with metformin,the proportion was 9.5%,there were 378 cases with normal glucose tolerance in patients without type 2 diabetes.the prevalence rate of type 2diabetes was 18.4%.Comparing the survival of metformin treatment group vs.not never metformin treatment group,The 6 months survival rate was 95.5%vs.63.5%,the 1 year survival rate was 77.0%vs.35.0%,and the 2 year survival rate was35.9%vs.15.1% respectively.The median survival time in metformin treatment group was 20 months(OR:2.425,95%CI:15.246~24.754),the median survival period of never metformin treatment group was 8 months(OR:0.521,95%CI: 6.979~9.021).Univariate analysis of OS revealed age,gender,smoking history,short-term weight loss,lymph node staging,DM,metformin treatment,bone,adrenal metastasis,targeted therapy,radiotherapy,surgery therapy,KPS score couid affect the overall survival of patients(P < 0.05).Univariate analysis of PFS showed that gender,smoking history,short-term weight loss,history of diabetes,metformin treatment,radiotherapy,targeted therapy,surgical treatment,the KPS score had statistical significance(P<0.05).And multivariate analysis showed that metformin treatment(OR: 0.559,95%CI: 0.344~0.910,P=0.019),gender(OR:0.619,95%CI:0.476~0.804,P<0.001),short-term weight loss(OR: 3.197,95%CI:2.069~4.940,P < 0.001),bone metastasis(OR: 1.690,95%CI:1.362~2.097,P<0.001),radiotherapy(OR:0.573,95%CI:0.456~0.722,P<0.001),targeted therapy(OR:0.545,95%CI:0.413~0.719,P<0.001),KPS score(OR:0.677,95%CI: 0.535~0.857,P=0.01)were considered independent prognostic factors for OS(P<0.05).What was more,metformin treatment(OR: 0.540,95%CI: 0.430~0.723,P=0.001),Gender(OR:0.558,95%CI:0.430~0.723,P<0.001),short-term weight loss(OR: 1.980,95%CI:1.305~3.004,P=0.001),radiotherapy(OR:0.727,95%CI:582~0.907,P=0.005),targeted therapy(OR: 0.516,95%CI: 0.392~0.680,P < 0.001),KPS score(OR: 0.656,95%CI: 0.521 ~0.826,P < 0.001)were identified as indepent prognostic factors for PFS(P<0.05).Conclusion: To conclude,metformin used by diabetes mellitus patients with brain metastases from non-small cell lung cancer might prolong OS(overall survival,OS)and PFS(progression free survival,PFS)in patients with non-small cell lung cancer with brain metastases;and in patients with diabetes in the course of the disease,oral hypoglycemic drugs such as metformin did benefit the survival of patients.