Research On The Relationship Between The Characteristics Of Pulmonary Structural Remodeling In COPD And The Prognosis Of Patients With Advanced Lung Squamous Cell Carcinoma

ObjectiveBy observing the changes of lung airway structure on imaging in patients with advanced lung squamous cell carcinoma and combining with relevant clinicopathological,functional and other basic features,this research analyzed the relationship between different types of pulmonary remodeling changes in COPD and prognosis in patients with lung squamous cell carcinoma,aiming to provide objective imaging basis for comprehensive assessment of prognosis in patients with advanced lung squamous cell carcinoma.Methods1.Clinical data collectionData of patients with advanced lung squamous cell carcinoma admitted to the Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Naval Medical University from January 2017 to December 2021 were collected,and 278cases were finally screened into the research according to strict inclusion and exclusion criteria.General clinical data,including age,sex,smoking history,BMI,PS score,TNM stage,histopathology,Ki-67,treatment regimen,peripheral blood tumor markers,D-dimer,CRP,erythrosediment and lung function indexes,were collected through the hospital information management system（HIS）,electronic medical record system（EMR）and laboratory information system（LIS）.2.Imaging data collectionThe Medical Imaging System and Synapse 3D image archive and transmission system were used to conduct 3D reconstruction of chest CT images to obtain Goddard score,percentage of airway wall thickness（WT%）as semi-quantitative index of lung structure remodeling and emphysema index（EI%）,percentage of airway wall area（WA%）as quantitative index.According to the semi-quantitative and quantitative indexes,lung remodeling was divided into airway remodeling dominant type,emphysema dominant type and mixed type.The types of emphysema and obstructive inflammation were obtained by manual radiograph review.3.Follow-up data collectionProgression-free survival（PFS）and overall survival（OS）data were obtained through a combination of hospital information management system,outpatient electronic case system and telephone contact.The follow-up period ended on October 31,2022.Truncated values included patients lost to follow-up and patients who survived beyond the study termination date.4.Statistical analysis methodsIn the measurement data,the normal distribution was represented by mean±standard deviation and T-test was used,while the skew distribution was represented by quartile and Mann-Whitney U or Kruskal-wallis H test.Count data were expressed as percentage（%）byχ2 test or Fisher exact probability method.Spearman rank correlation analysis was used for correlation analysis.Kaplan-Meier survival curve and log-rank test was used to evaluate the differences in PFS,OS.Univariate and multivariate analyses of PFS and OS were conducted by COX proportional hazard regression model.P<0.05 was considered to be statistically significant.Results1.General clinical data278 patients with advanced lung squamous cell carcinoma were enrolled,including194 patients（69.8%）with COPD and 84 patients（30.2%）without COPD.The proportion of patients over 60 years old（80.4%vs 65.5%）and male（93.8%vs 79.8%）in COPD group was higher,and the smoking index（45 vs 20 pack-years）and blood CEA level（4.34 vs 3.28 ng/ml）were higher.Patients without COPD had more treatment lines,longer m PFS（8 vs 6 months）and m OS（18.5 vs 14 months）.2.Comparison of pulmonary remodeling indexes between patients with COPD and those without COPDGoddard score（6 vs 6 vs 7.5 points,P=0.007）,WA%（42.09%vs 47.01%vs 51.22%,P=0.001）,WT%（24.73%vs 27.37%vs 33.15%,P<0.001）increased with increasing GOLD grade in the combined COPD group,the proportion of mixed type increased in the semi-quantitative classification of lung remodeling（17.4%vs 28.8%vs 57.1%）.Compared with patients without COPD,the proportion of mixed type in semi-quantitative classification of lung structural remodeling in patients with COPD increased（27.3%vs15.5%,P<0.05）,Goddard score,EI%,WA%and WT%all showed an increasing trend,but the difference was not statistically significant.3.Correlation analysis of pulmonary function and pulmonary structural remodeling indexes in patients with COPDGoddard score was negatively correlated with FEV₁/FVC,FEF75,FEF50 and MMEF（r=-0.329,-0.4,-0.345,-0.365,all P<0.001）;WA%,WT%were also negatively correlated with FEV₁%（r=-0.303,-0.332,P=0.001,<0.001）.4.Comparison of indicators of lung remodeling at diagnosis and progression of squamous cell carcinomaCompared with the time of diagnosis,the Goddard score[6（5,7）vs 6（5,8）]and EI%[14.5%（8.9%,20.63%）vs 15.9%（10.6%,21.8%）]were higher at the progression of advanced lung squamous cell carcinoma（P<0.001）.No matter semi-quantitative or quantitative typing,the proportion of mixed type increased（24.7%vs 39.2%,36.1%vs43.1%）and airway remodeling dominant type decreased（66.3%vs 50.2%,42.0%vs36.9%）.The difference was statistically significant.5.Effect of lung remodeling on PFS and OS in patients with advanced lung squamous cell carcinomaAmong all the patients,according to the semi-quantitative classification of lung structural remodeling,m PFS and m OS of mixed type were the shortest（4 and 10 months）,and compared with those of airway remodeling dominant type（7 and 20 months）and emphysema dominant type（9 and 20 months）,both differences were significant（P<0.001,P<0.01）.According to the quantitative classification of pulmonary structural remodeling,the results were the same as the semi-quantitative classification,the m PFS of emphysema dominant type,airway remodeling dominant type and mixed type showed a decreasing trend,but there was no significant difference among the three groups,while the m OS of mixed type（15 months）and airway remodeling dominant type（14 months）were significantly shorter than that of emphysema dominant type（24 months）,P<0.013 and0.011.In the group with COPD,according to the semi-quantitative classification of lung structural remodeling,m PFS and m OS of mixed type（4.5 and 9 months）was significantly shorter than those of airway remodeling dominant type（6.5 and 17 months）and emphysema dominant type（9.5 and 19 months）,both differences were significant.According to the quantitative classification of pulmonary structural remodeling,m PFS and m OS were gradually shortened among emphysema dominant type,mixed type and airway remodeling dominant type,but P>0.05.At the same time,it was found that m PFS and m OS in the group with COPD were significantly shorter than those in the group without COPD（6 vs 8 months,P=0.025;14 vs 23 months,P=0.006）.With the increase of GOLD grade,m PFS and m OS were gradually shortened（8 vs 6 vs5.5 months;23 vs 15 vs10months）,and there was statistical difference among the three groups.6.Analysis of prognostic factors of advanced lung squamous cell carcinomaA total of 22 factors were included in univariate COX risk regression analysis of PFS for advanced lung squamous cell carcinoma,suggesting that PS score,COPD,confirmed stage,first-line treatment,Goddard score,WT%,remodeled semi-quantitative typing,WA%,Ki-67,blood CEA were risk factors for its progression（P<0.05）.Multivariate analysis suggested that WA%and Ki-67 increased,late diagnosis stage and mixed semi-quantitative typing were independent risk factors for the progression of advanced lung squamous cell carcinoma,and first-line chemotherapy+immunotherapy were protective factors.Higher Ki-67,WA%and Goddard score in patients with COPD were independent risk factors for tumor progression.A total of 22 factors were included in OS univariate COX risk regression analysis for advanced lung squamous cell carcinoma.It was suggested that PS score,COPD,confirmed stage,treatment regimen,Goddard score,WT%,remodeled semi-quantitative typing,WA%,remodeled quantitative typing,Ki-67,SCC,CEA,CYFRA21-1,CRP,erythrocyte deposition and D-dimer were risk factors for death（all P<0.05）.Multivariate analysis showed that higher PS score,Goddard score,WT%,Ki-67,CYFRA21-1,ESR and non-retrograde treatment,semi-quantitative emphysema dominant type,semi-quantitative mixed type were independent risk factors for advanced lung squamous cell carcinoma.COX analysis in COPD group indicated that higher Ki-67,semi-quantitative mixed type and male were independent risk factors for death.Conclusion1.The measurement index of chest HRCT is proportional to the severity of COPD,and is significantly correlated with the evaluation index of lung function,which can be used to evaluate the pulmonary remodeling caused by COPD.2.Patients with advanced lung squamous cell carcinoma all have different degrees of lung structural remodeling.The aggravation of emphysema was more serious than that of airway wall thickening during tumor progression,and transformation from airway remodeling dominant type to mixed type.The change of emphysema index plays a more important role in the progression of advanced lung squamous cell carcinoma.3.Patients with advanced lung squamous cell carcinoma with mixed type lung remodeling have the worst prognosis,it and Ki-67 are both independent risk factors for poor PFS and OS in patients with advanced lung squamous cell carcinoma,while chemotherapy+immunotherapy is protective factors for PFS and OS.In addition,late tumor stage and higher WA%were also independent risk factors for PFS;The elevation of PS score,Goddard score,WT%,CYFRA21-1,ESR and COPD,emphysema dominant type lung remodeling were also independent risk factors for OS.