The Prognostic Role Of Clinicopathological Factors Besides TNM Stage To The Common Thoracic Malignances

With the increase in life expectancy,cancer is a major public health problem worldwide and is the second leading cause of death.Cancer incidence and mortality have also been increasing in China.The results indicated that an estimated 4,292,000 new cancer cases and 2,814,000 cancer deaths would occur in China in 2015.Lung cancer and esophageal cancer are the two dominant thoracic cancers.Lung cancer is the most common incident cancer and the leading cause of cancer death.Esophageal cancer is also commonly diagnosed and is identified as fourth cause of cancer death.Although the treatment strategies such as surgical techniques,targeted therapy,chemotherapy and radiotherapy were greatly improved,the survival of patients was still unsatisfying.Therefore,identifying patients who benefit from complete surgical resection and further adjuvant therapies will improve the patients’5-year survival rate.The TNM Classification of Malignant Tumors(T for tumor,N for node and M for metastasis)was originally developed by Pierre Denoix in the 1940s and has now become the worldwide accepted basis of cancer staging.The TNM staging system is an important tool to assess prognosis,guide therapy,and formulate treatment protocols.However,heterogeneous clinical courses are frequently observed even within the same tumor stage.So many other clinicopathological factors predicting the outcome of cancer patient have been investigated in past 10 years.The status of regional lymph node(LN)is a strong prognostic indicator and has a major impact on treatment decisions for patients with non-small cell lung cancer(NSCLC).In the eighth TNM staging system proposal for NSCLC recently,classification of N stage is based on anatomical position of positive lymph nodes but not the positive lymph number and ratio,in which ipsilateral peribronchial and/or hilar lymph node metastasis are defined as pNl;ipsilateral mediastinal and/or subcarinal metastasis as pN2 and contralateral mediastinal,contralateral hilar,or supraclavicular metastasis as pN3.In some other solid tumors,such as breast,gastric,and colorectal cancer,the number of metastatic lymph nodes has been considered in the TNM staging systemBefore 1987,tumor length had been used as a staging criterion to predict esophageal cancer prognosis but has been removed in the current TNM staging system.The 7th esophageal cancer T staging system mainly depends on the depth of tumor invasion,in which tumor invades the lamina propria or muscularis mucosae are defined as Tla,tumor invades the submucosa as T1b,tumor invades the muscularis propria as T2,tumor invades the adventitia as T3,and tumor invades adjacent structures as T4.But the TNM stage for other tumors such as lung cancer or breast cancer,the size or length of the primary tumor were taken into account.The study was divided into two parts.In the first part,we used the Surveillance,Epidemiology,and End Results Database aiming to expand the sample volume to identify the value of positive lymph node number or ratio in prognosis.In the second part,we collected the clinicopathological factors of 498 ESCC patients who received surgery in our hospital.A time-dependent receiver operating characteristic(ROC)curve and a regression tree for survival were used to identify the cut-off point of tumor length.Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic role of tumor length to ESCC.CHAPTER I.Prognostic and Predictive Effects of Positive Lymph Node Number or Ratio in NSCLCBACKGROUND:For patients diagnosed with early-stage non-small cell lung cancer(NSCLC),surgical resection remains the mainstay of therapy.The status of regional lymph node(LN)is a strong prognostic indicator and has a major impact on treatment decisions for patients.In the eighth TNM staging system proposal for NSCLC recently,classification of N stage is based on anatomical position of positive lymph nodes,in which ipsilateral peribronchial and/or hilar lymph node metastasis are defined as pNl;ipsilateral mediastinal and/or subcarinal metastasis as pN2 and contralateral mediastinal,contralateral hilar,or supraclavicular metastasis as pN3.However,many studies have found that the number and ratio of positive lymph nodes were independent risk factors.Local recurrence and distal metastasis are the dominant procedures of cancer progression and the main causes of cancer mortality even for the NSCLC patients at early stage who received surgery.However,there are some harboring microscopic diseases among these operable patients and postoperative radiation might be performed aiming to reduce local recurrence and improve the outcome.Obviously,not all these patients could get benefits from it;some even could obtain detrimental results,so which group people should receive postoperative radiation was an important issue that has not been figured out.It is crucial to find predictive factors to determine the conduction of radiation after surgery.METHODS:We aimed to expand the sample volume to identify the value of positive lymph node number or ratio in prognosis and predictive effect for postoperative radiation.Clinicopathological characters of 109,026 NSCLC patients were collected from the SEER Database.Kaplan-Meier curves and cox regression methods were used for survival analysis.RESULTS:Compared with positive lymph node number equal to 0,1-3 and>4 groups were independent prognostic factors(1-3:HR =2.856,p<0.001;≥4:HR=3.358,p<0.001),so as the 0-50%and>50%positive lymph node ratio groups(0-50%:HR =2.124,p<0.001;>50%:HR= 3.358,p<0.001).And in the groups of N2&positive lymph node number≥4 and N2&positive lymph node ratio>50%,postoperative radiation was related to positive prognosis of NSCLC patients.CONCLUSION:In conclusion,positive lymph node number or ratio was associated with survival as an independent indicator in NSCLC.They also had predictive effects for postoperative radiation,while N nodal stage not.CHAPTER II.The prognostic value of tumor lengthto resectable esophageal squamous cell carcinoma:a retrospective studyBACKGROUND:Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies.ESCC is endemic in many parts of the world,particularly in Asian countries,including China.Although the treatment strategies such as surgical techniques,chemotherapy and radiotherapy were greatly improved,the.survival of patients with EC was still unsatisfying.Therefore,it is important to identify the prognostic factors and to determine the optimal treatment strategies for the improvement of 5-year survival rate.TNM stage is the most important prognostic factor.In the 7th TNM staging system for EC released by UICC/AJCC,the ESCC and EAC were separated staged.And high-grade intraepithelial neoplasia was defined as Tis period.The T4 was subcategorized as T4a and T4b respectively,according to the different invaded structures.The degree of tumor differentiation and tumor location were also considered for the ESCC patients.However,many studies have found that the prognosis is different even for patients with the same pTNM stages,suggesting that other possible clinical factors may affect the prognosis,such as the anatomical site of positive lymph nodes,circumferential resection margin and tumor length.Historically tumor length has been used as a part of the staging criteria.In the 1983 version of TNM staging system for EC,a clinical criteria included tumor length was used.Tumors length less than 5 cm and were not circumferential were considered T1,whereas tumors length greater than 5 cm or that were causing obstruction or were circumferential were defined as T2.With revisions of the staging system,tumor length was replaced by the depth of tumor invasion.The tumor length can be determined by various methods,including radiographic measurements,endoscopic measurements,intraoperative measurement and pathologist’s measurement.The most common method is measured by histopathological specimens after surgical resection.The prognostic role of tumor length for EC is still controversial which may be caused by the heterogeneity between different studies.The purpose of this study is to analyze the relationship between tumor length and other prognostic factors.At the same time,the appropriate cut-off value of tumor length was determined.This study explored the effect of tumor length,in addition to tumor depth and lymph node involvement,on survival in patients with esophageal squamous cell carcinoma.METHODS:A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study.Pathological details were collected,which included tumor type,TNM stage,and differentiation.Other collected information was:the types of esophageal resection,ABO blood group,family history and demographic and lifestyle factors.A time-dependent receiver operating characteristic(ROC)curve and a regression tree for survival were used to identify the cut-off point of tumor length,which was 3 cm.Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC.RESULTS:The 1-,3-,5-year overall survival rates were found to be 82.5%,55.6%,and 35.1%,respectively.Patients who had larger tumor length(>3 cm)had a higher risk for death than the rest patients.From the univariate Cox proportional hazards regression model,the overall survival rate was significantly influenced by sex,the depth of the tumor,lymph node involvement(either as dummy or continuous variables)and tumor length(p=0.023,p<0.001,p<0.001,p<0.001).Using these four variables in the multivariate Cox proportional hazard regression model,we found that the overall survival was significantly influenced by all variables except sex(HR:0.72,95%CI(0.49-1.08),p=0.11).Therefore,in addition to the depth of the tumor and lymph node involvement(as either dummy or continuous variables),the tumor length is also an independent prognostic factor for ESCC(HR:1.53,95%CI(1.06-2.22),p=0.025;HR:1.60,95%CI(1.21-2.13),p<0.001;HR:1.37,95%CI(1.18-1.60),p<0.001;).The overall survival rate was higher in a group with smaller tumor length(≤3 cm)than those patients with larger tumor length(>3 cm),no matter what the tumor stage was.CONCLUSION:The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy.The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.