| Lung cancer has been the most common cancer in the world,with the third incidence among all cancers.It was also the most common cause of death from cancers worldwide.Owing to the sustained growth of tobacco consumption,environment contamination and changes in lifestyle,lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death in our country.And thus it has been one of the major disease which forming a threat to human life and health.Lung cancer can be mainly divided into small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC),and the latter accounts for about 85%of the total number of lung cancer.Despite the advance of diagnosis and treatment technologies,NSCLC has a very poor prognosis,with the estimated five-year survival rate at about 17.7%in America,only 16.1%in China.The Tumour-Node-Metastasis(TNM)classification system based on the extent of the primary tumor,involvement of regional lymph nodes and spread to distant sites forms the basis for staging and has vital effects on prognostic evaluation and treatment options.Recently,with the wide use of low-dose computed tomography(LDCT)in high-risk population,more and more early stage NSCLC(stage Ⅱ-Ⅱ)patients were diagnosed,however,the estimated five-year survival rate was only 36%-73%.So it is of great importance to study the prognosis of early stage NSCLC,for the reasons of studying natural history of the disease,guiding individual treatment,improving the survival and life quality of patients and decreasing the economic burden of the disease.Clinically,the main therapy for early stage NSCLC patients is surgery,with or without adjuvant chemotherapy or radiotherapy.However,when giving the same treatment for some patients with the same clinical staging,significant difference between the individual prognosis of cancer do exist,which indicates that some other important factors may affect the early stage NSCLC survival.Some literatures reported that age,gender,performance status,family history of cancer,smoke status,surgery type,histology,cell differentiation and tumor location might also contribute to the prognosis of early stage NSCLC.While,because of the difference of sample sizes and the interference of treatment factors,the researchers did not obtain the consistent results.So,it’s crucial to further explore other prognostic factors for early stage NSCLC with large sample and more rigorous design.Meanwhile,although we have known the prognostic factors,it is difficult to predict the survival rate at the individual level.So,there is an urgent need to develop the new method for predicting the individual prognosis in early stage NSCLC population.Nomogram is widely used as prognostic device in oncology and medicine.It is a pictorial representation of a complex mathematical formula and uses biological and clinical variables,such as tumour grade and patient age,to determine a statistical prognostic model that generates a probability of a clinical event,such as cancer recurrence or death,for a particular individual.Recently,few study has referred to nomograms that predicted overall survival after surgery treatment in early stage NSCLC patients,particularly in Chinese population.Thus,we aimed to construct a prognostic nomogram with demographic and clinicopathologic variables to investigate whether such nomogram provided accurate prediction for overall survival of early stage NSCLC patients after surgery resection and guide clinical practice.We performed a prospective clinical follow-up study in a cohort of 643 early stage NSCLC patients.All patients were consecutively recruited between September 2002 and December 2011 from the Cancer Hospital of Jiangsu Province and the First Affiliated Hospital of Nanjing Medical University.All patients were followed up through telephone contacts from the time of enrollment until death or last contact(last follow-up:July 2015).Additionally,the latest medical records were also checked as a complement.Finally,a total of 458(71.23%)patients who had both follow-up and available clinical information were enrolled in this study.EpiData(version 3.02)software was applied for data entry double track and error checking,and R software(version 3.2.3)was used for statistical analyses.In the univariate analysis,log-rank test was used to compare the survival time for categorical variables and survival curves were depicted using the Kaplan-Meier method.Next,variables with P value<0.05 through above analysis were entered into multivariate Cox regression model to identify independent prognostic factors.A nomogram was then formulated based on these independent prognostic factors(P<0.05)in the final model and delineated by using the R package ’rms’.The selection of the final model was using a backward step-down process with the Akaike information criterion(AIC).The performance of the nomogram was assessed by Harrell’s concordance index(C-index).Bootstrap resamples(1000 times)was used for internal validation and provided a relatively unbiased estimate of C-index.Then,calibration plots for 3-,5-year overall survival probability were depicted to compare the predicted survival and observed survival after bias correction of bootstrap resample(1000 times).The median follow-up time was 42.0 months(range,4.4-130.9 months),140 patients died from NSCLC and the median survival time(MST)was 102.5 months.The estimated three-year survival rate was 75.95%,and five-year survival rate was 64.45%.The results of the univariate analysis indicated that patients with poor differentiation and less than five stations of sampled lymph nodes had worse prognosis(log-rank P<0.05).Additionally,pathologic T,pathologic N and pathologic TNM stage were also significantly associated with survival time of early stage NSCLC patients(log-rank P<0.05).Then,multivariate Cox regression analysis further revealed that differentiation,station of sampled lymph nodes,pathologic T and pathologic N remained as independent prognostic factors for overall survival.Moreover,a nomogram incorporating above four independent prognostic factors was constructed to predict the 3-year and 5-year overall survival for early stage NSCLC patients.For predictive accuracy of overall survival,nomogram had a larger bia-corrected C-index than conventional TNM staging system(0.622 vs.0.597).Finally,the calibration plot demonstrated that the predicted 3-year and 5-year overall survival probabilities corresponded closely with the actually observed probabilities.In conclusion,we developed and validated a nomogram incorporating available clinicopathological markers to predict survival in resected early stage NSCLC patients and it showed better prediction value of survival than standard TNM staging.The nomogram may guide appropriately postoperative decisions including intensified treatment and rigorous surveillance,and improve the prognosis. |
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