Study On The Correlation Between Traditional Chinese Medicine(TCM)constitution,syndrome Type And Immune-Related Adverse Events(irAEs)in Advanced Non-small Cell Lung Cancer(NSCLC)

Background and Objective:To study and investigate the TCM constitution types and the distribution characteristics of TCM syndrome types of patients with advanced non-small cell lung cancer(NSCLC),and explore the comprehensive diagnosis and treatment mode of "body differentiation,disease differentiation and syndrome differentiation" of TCM in the treatment of advanced NSCLC.Through the observation and exploration of immune-related adverse events(irAEs)of advanced NSCLC immune checkpoint inhibitors combined with chemotherapy(hereinafter referred to as immunochemotherapy).We analyzed the influencing factors of common irAEs and explored the relationship between TCM constitution and syndrome types and the occurrence of irAEs during immunochemotherapy in advanced NSCLC patients,so as to clarify the TCM constitution,TCM syndrome types,population characteristics and influence patterns of irAEs occurring.Materials and methods:1.116 patients with stage IIIB-IV NSCLC(negative driver gene)who were treated with first-line PD-1 antibody combined with chemotherapy in the Department of Oncology,First Affiliated Hospital of Dalian Medical University from December 2021 to December 2022 were selected.According to the guidelines of NCCN and CSCO,the PD-1 antibody was mainly Tislelizumab and Camrelizumab,43 cases of squamous cell carcinoma were mainly treated with paclitaxel plus platinum,and 73 cases of adenocarcinoma were mainly treated with pemetrexed plus platinum.2.The clinical case observation table "TCM syndrome scoring scale" was designed according to the "Chinese Society of Traditional Chinese Medicine Standard Guide for the Diagnosis and Treatment of Tumor",and the patients were inquired in detail.At least two TCM physicians at the level of deputy chief physician or above will conduct detailed consultation with the patients and register the TCM syndrome types for each patient.3.Informed consent was obtained from the patients and theirfamilies,and the "TCM Physique Classification and Judgment Form" was filled out based on the actual condition of the patient for almost one year prior to receiving treatment,and those who could correctly understand the questions filled out the form themselves;and those who are old or unable to understand the problem correctly should be completed with the help of researchers with professional knowledge of traditional Chinese medicine.Determine and sort out the TCM constitution types of patients.4.The patients receiving immunotherapy were evaluated before treatment,and reexamined every 2 cycles during the treatment period to observe whether various adverse reactions occurred after immunotherapy,record the clinical manifestations of adverse reactions,determine the grading of adverse reactions and record the dynamic changes.Considering that immune combination chemotherapy adverse reactions have partial overlap and are difficult to distinguish,this study mainly recorded adverse reactions outside the hematological system.5.All investigation and research data are entered into Excel table,database is established,SPSS 26.0 statistical software is used for statistical analysis,chi-square test and Fisher test were used for single factor analysis,and binary logistic regression model is used for multiple factor analysis.Results:1.The distribution characteristics and correlation of TCM constitution and TCM syndrome types in advanced NSCLC(1)TCM constitution distribution: 9 TCM constitution types were distributed in 116 patients,and the general constitution was biased constitution,of which qi deficiency constitution(34 /116,29.31%),phlegm dampness constitution(23 /116,19.83%),and yang deficiency constitution(16 /116,13.79%)were the most common.(2)TCM syndrome types: Among 116 lung cancer patients,spleen deficiency and phlegm dampness syndrome(36 /116,31.03%),qi and yin deficiency syndrome(25 /116,21.55%)and qi stagnation and blood stasis syndrome(22 /116,18.97%)are the most common,other yin deficiency and internal heat syndrome(19 /116,16.38%),kidney yang deficiency syndrome(14 /116,12.07%).(3)There was a correlation between TCM constitution and TCM syndrome types in patients with advanced NSCLC(p=0.002 < 0.05),including yang deficiency constitution(p=0.001 < 0.05),yin deficiency constitution(p=0.016 < 0.05)and blood stasis constitution(p=0.019 < 0.05),phlegm dampness constitution(p=0.005< 0.05).2.Univariate analysis of irAEs in advanced NSCLC immunochemical treatment(1)Select five common TCM constitutions(qi deficiency constitution,yang deficiency constitution,yin deficiency constitution,Phlegm dampness constitution,and balanced constitution)of patients with advanced NSCLC in the study and conduct correlation analysis with the occurrence of irAEs in immunochemical treatment,and the results were statistically significant(p=0.002 < 0.05).(2)There was no statistical difference between the correlation analysis of TCM syndrome types and irAEs in patients with advanced NSCLC(p>0.05).(3)The univariate analysis of the occurrence of irAEs in immunochemical treatment showed that there were significant statistical differences between the occurrence of irAEs in immunochemical treatment and the factors such as Phlegm-dampness constitution,qi deficiency constitution,age,PD-L1 expression,smoking or not,among which phlegm dampness constitution(p=0.002 < 0.05),qi deficiency constitution(p=0.007 < 0.05),age(p=0.009 < 0.05),PD-L1 expression(p=0.002 < 0.05),smoking or not(p=0.001 <0.05).3.Multivariate analysis of irAEs in advanced NSCLC immunochemical treatment(1)The influence of phlegm dampness constitution on irAEs in NSCLC patients with immunochemical treatment was statistically significant(OR=10.947,95% CI 2.153-55.663,p=0.004 < 0.05);(2)The high expression of PD-L1(≥ 50%)had a statistically significant effect on the occurrence of irAEs in NSCLC patients after immunochemotherapy(OR=50.264,95%CI 3.457-730.740,p=0.004 < 0.05);(3)The influence of advanced age(age>60 years old)on the occurrence of irAEs in NSCLC patients with immunochemotherapy was statistically significant(OR=3.749,95% CI 1.038-13.537,p=0.044 < 0.05);(4)The influence of smoking history on the occurrence of irAEs in NSCLC patients with immunochemotherapy was statistically significant(OR=7.834,95% CI1.965-31.231,p=0.004 < 0.05).Conclusions:1.The TCM constitution distribution of patients with advanced NSCLC mainly consists of qi deficiency constitution,phlegm-dampness constitution and yang deficiency constitution,and the TCM syndrome distribution is mainly spleen deficiency and phlegm dampness syndrome,qi and Yin deficiency syndrome and qi stagnation and blood stasis syndrome.Different constitution types are correlated with TCM syndrome distribution.2.The correlation between TCM constitution and the occurrence of irAEs was statistically different.3.There was no statistical difference in the correlation between TCM syndromes and the occurrence of irAEs.4.Phlegm dampness constitution,advanced age(age > 60 years),high expression of PD-L1(≥50%)and smoking history are risk factors for the occurrence of irAEs in NSCLC patients with immunochemotherapy.