Prognostic And Predictive Value Of The Novel Lung Adenocarcinoma Classification System In Early Stage Patients

PART ? PROGNOSTIC AND PREDICTIVE VALUE OF THE NOVEL CLASSIFICATION OF LUNG ADENOCARCINOMA IN PATIENTS WITH STAGE I INVASIVE LUNG ADENOCARCINOMABACKGROUND:Lung cancer continues to be a life-threatening disease for the high morbidity and mortality in China.Despite curative-intent surgery,post-surgical survival remains unsatisfied.The 5-year survival rate was only 66%for stage IB patients.Therefore,it is important to find an effective prognostic predictive model to improve the long-term prognosis for early stage lung adenocarcinoma patients.In 2011,a new lung adenocarcinoma classification system proposed by the IASLC/ATS/ERS.Classification of individual tumors according to the most predominant subtype and the percentages of the subtypes were also reported.The utility of this novel classification in predicting patients'survival has been widely reported,indicating that solid predominant subtype was associated with poorer DFS and OS.However,the prognoses of patients with solid minor components still have not been thoroughly studied.Besides,according to the IASLC staging project,the 8^th TNM classification for lung cancer has been enacted in January 2017.In this study,we carried a large cohort based on the 8^th TNM staging classification,to evaluate the survival among patients with solid minor components in predicting the prognosis.METHODS:A total of 3308 stage ? lung adenocarcinoma patients were included in our cohort.Invasive adenocarcinomas were classified into 5major subtypes according to the predominant pattern,including lepidic?LEP?,acinar?ACN?,papillary?PAP?,micropapillary?MIP?and solid?SOL?predominant subgroup.In order to determine the impact of solid component on patient's prognosis,patients were divided into 3 groups based on the percentages of solid components in tumor:solid predominant?S predominant?,solid minor?S minor;LEP,ACN,PAP or MIP predominant pattern,containing solid component?and solid absent?S absent?group.Disease-free survival?DFS?and overall survival?OS?were analyzed to evaluate survival difference among patients with different histological patterns using the Kaplan-Meier approach and multivariable Cox models.RESULTS:The median follow-up time was 36.97 months?range,0.3 to73.8 months?.In univariable analysis,solid subgroup showed the worst outcome for both DFS and OS.Univariable analysis based on the percentage of solid component presented in tumor tissue indicating that,there were significant worse DFS?HR,2.74;95%CI,1.95-3.85;p=.000?and OS?HR,3.00;95%CI,1.84-4.90;p=.000?for S minor compared with S absent group.However,no significant DFS?HR,1.41;95%CI,0.87-2.30;p=.161?or OS?HR,1.60;95%CI,0.83-3.09,p=.159?difference between S predominant and S minor groups.Subgroup analysis achieved the same results.CONCLUSION:According to the 2011 IASLC/ATS/ERS classification of lung adenocarcinoma,for stage ? lung adenocarcinoma patients,solid minor components were correlated to unfavorable DFS and OS compared with solid absent pattern.This finding may be beneficial for stratification of higher-risk patients for positive postsurgical management.PART ? SUBTYPE CLASSIFICATION OF LUNG ADENOCARCINOMA PREDICTS BENEFIT FROM ADJUVANT CHEMOTHERAPY IN STAGE IB PATIENTS UNDERGOING SURGICAL RESECTIONBACKGROUND: Lung cancer is one of the most leading cause of cancer death worldwide.Adenocarcinoma is the most common histologic subtype,more than 80% to 90% of which demonstrated heterogeneous histologic patterns.Despite the current standard completely surgical resection for patients with early stage lung adenocarcinoma,30%-40% of these patients still will relapse.The National Comprehensive Cancer Network?NCCN?guideline suggested that patients in stage IB should consider adjuvant chemotherapy with high-risk factors including tumor size greater than 4cm,visceral pleura invasion,lymphovascular invasion,poorly differentiated,wedge resection or incomplete lymph node sampling.However,this recommendation is category 2B,lacking for high-level evidence and uniform NCCN consensus.So the benefit of adjuvant chemotherapy?ACT?among stage IB patients remains controversial.Several studies investigated the prognostic and predictive value of the IASLC/ATS/ERS classification in stage IB lung adenocarcinoma patients.However,the predictive value of the classification for benefit from adjuvant chemotherapy remains unknown.METHODS: A total of 804 stage IB lung adenocarcinoma patients were included in our cohort.Invasive adenocarcinomas were classified into 5 major subtypes according to the predominant pattern,including lepidic ?LEP?,acinar?ACN?,papillary?PAP?,micropapillary?MIP?and solid?SOL?predominant subgroup.In order to figure out the impact of solid component on patient's prognosis,patients were divided into 3 groups based on the percentages of solid components in tumor: solid predominant?S predominant?,solid minor?S minor;LEP,ACN,PAP or MIP predominant pattern,containing solid component?and solid absent?S absent?group.Disease-free survival?DFS?and overall survival?OS?were analyzed to evaluate survival difference among patients with different histological patterns using the Kaplan-Meier approach and multivariable Cox models.RESULTS: For patients in stage IB,patients with solid predominant derived DFS?HR,0.33;95%CI,0.11-1.02;p=.044?but not OS?HR,0.61;95%CI,0.21-1.77;p=.360?benefit from ACT.Univariable analysis based on the percentage of solid component presented in tumor tissue indicating that,there were no significant DFS?HR,1.45;95%CI,0.78-2.69;p=.237?or OS?HR,1.60;95%CI,0.72-3.57 p=.249?different between S predominant and S minor groups.However,patients in S minor group could not achieve DFS?HR,1.04;95%CI,0.49-2.22;p=.922?and OS?HR,0.49;95%CI,0.13-1.90;p=.291?benefit from ACT.CONCLUSION: For stage IB lung adenocarcinoma patients,Solid minor components predict a significant worse prognosis compared with solid absent pattern.However,ACT may be unhelpful to improve outcome of stage ?b patients with solid minor components after surgery.