| Background: The incidence of lung cancer ranks the first among malignant tumors in China,and it is also the leading cause of death in the worldwide.In recent years,the incidence of brain metastases of lung cancer has increased year by year.About 10%～20% of lung cancer patients have brain metastases at the time of initial diagnosis.Even for lung cancer patients receiving systemic therapy,the median survival time is only 3～11 months.Therefore,early identification of risk factors and prognostic factors of lung cancer with brain metastases and intervention are extremely important to improve symptoms and prolong survival time.Objective: To explore the risk factors of brain metastases in patients with lung cancer and the clinical characteristics and prognostic factors of patients with brain metastases.Moreover,a nomogram will be constructed to predict the overall survival of lung cancer patients diagnosed brain metastasis,thereby providing evidence for potential treatment plans and clinical prognosis evaluation.Methods: SEER*Stat was used to collect clinical data of 128,698 patients with primary lung cancer from 2010 to 2016 in SEER database.The χ2 test was used to compare the differences in clinical characteristics between the brain metastasis group(n=17209)and the non-brain metastasis group(n=111489).Binary Logistic regression was used to identify risk factors for brain metastasis.Kaplan-Meier survival curve and log-rank were used for survival analysis.Multivariate COX regression model was used to analyze independent risk factors affecting the prognosis of patients with lung cancer with brain metastasis.Then,lung cancer patients diagnosed brain metastasis(n= 17209)were randomly assigned to the training group(n = 12026)and the validation group(n = 5183).The independent prognostic factors of lung cancer patients diagnosed brain metastasis in the training group were determined by univariate and multivariate Cox regression model,and the statistically significant predictors were selected to construct a nomogram.The accuracy of the nomogram were assessed by calculating C-index and drawing calibration curves and ROC Curves.Finally,the risk stratification system based on the prediction score of the prognostic model was established.Results: A total of 128,698 lung cancer patients were included,including 17,209(13.4%)patients with brain metastases and 111,489(86.6%)patients without brain metastases.Male,white,married,and adenocarcinoma patients were more common in the two groups.The age was mostly 61～80 years old.The tumor size was mostly2～4cm,and the histological grade was mostly grade III.The statistically significant factors in the clinical characteristics of patients with brain metastasis and non-brain metastasis included: age,race,marital status,degree of differentiation,tumor size,histological type,T stage,N stage,radiotherapy,chemotherapy,and location of metastasis.The median survival time in the brain metastasis group was 6 months,and the median survival time in the non-brain metastasis group was 17 months(P <0.05).The binary logistic regression results show that female,young people,other races(including Indian,Asian or Pacific Islander,etc.),low differentiation,tumor size at6～8cm,adenocarcinoma,low T stage,high N stage,combined with bone or liver metastasis were more likely to develop brain metastasis in patients with lung cancer(P <0.05).Kaplan-Meier survival analysis showed that patients who received chemotherapy had a longer overall survival(9 vs 2 months,95% CI: 2.481～2.672,P<0.001),and the median survival of patients who received radiotherapy and patients who did not receive radiotherapy were 6 and 3 months(95% CI: 1.042～1.130,P<0.001),respectively.The multivariate COX proportional hazard model suggests that gender,age,race,marital status,tumor size,histological type,degree of differentiation,T stage,N stage,combined with bone or liver metastasis,radiotherapy,and chemotherapy are all independent factors affecting the prognosis of patients with lung cancer with brain metastasis(P <0.05).A nomogram was constructed based on the above parameters.The C-indexes for the training and validation groups were0.715(95% CI: 0.709～0.721)and 0.721(95% CI: 0.713～0.729),respectively.The areas under the curve of the nomogram in the training group and the validation group at 1 year and 3 years were 0.8,0.744,0.700,and 0.747,respectively,indicating better predictive ability.According to the model prediction total score,the patients were divided into low-risk group: 52～222 points,intermediate-risk group: 223～327 points and high-risk group: 328～448 points.In the training set,the median survival of the low-,intermediate-and high-risk groups were 12,5,and 2 months,respectively;in the validation set,the median survival of the three groups were 11,5,and 2 months,respectively.The difference was statistically significant s among these three risk groups(P<0.0001).Conclusion: Patients with lung cancer with brain metastasis have unique clinicopathological characteristics.Patients with brain metastasis have a poor prognosis.Larger tumor diameters,poor differentiation,high N stage,bone metastasis,and liver metastasis are not only risk factors for brain metastasis in lung cancer patients,but also poor prognosis factors for patients with brain metastasis.the nomogram based on the SEER database has high predictive accuracy and clinical applicability,which can effectively predict the 1-year and 3-year survival rates of patients diagnosed lung cancer with brain metastasis.It is helpful for clinicians to guide patients to individualize assessment and treatment. |
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