Effects Of Radiation Dosimetry Parameters Of Cardiac,Pericardial And Pulmonary Artery On Immune Function Indicators,Prognosis And Survival In Locally Advanced Non-Small Cell Lung Cancer

Objective:Several studies have shown that the dosimetric parameters of the heart and pericardium may be related to the occurrence of cardiac adverse events?AEs?and survival after non-small cell lung cancer?NSCLC?radiation therapy?RT?.The purpose of this study was to analyze the correlation between RT dosimetric parameters of heart,pericardium and pulmonary artery and human immune function,cardiac function,and recent cardiac AEs,and its impact on prognosis and survival in patients with locally advanced NSCLC?LA-NSCLC?undergoing radical synchronous or sequential chemoradiotherapy through a single-center retrospective cases analysis.Methods:We performed a retrospective analysis of patients with LA-NSCLC who underwent radical chemoradiotherapy with dose?60Gy at the first oncology department of Shengjing Hospital,China Medical University from October 2014 to June 2019.Collect patients'baseline clinicopathological information?age,gender,Charlson comorbidity index,performance status score,clinical stage,pathology,etc.?,electrocardiogram before and after treatment,peripheral blood immunoinflammatory indicators?neutrophil-to-lymphocyte ratio?NLR?,lymphocyte-to-monocyte ratio?LMR?,platelet-to-lymphocyte ratio?PLR??,peripheral blood cardiac markers?creatine kinase?CK?,creatine kinase isoenzyme?CK-MB?,lactate dehydrogenase?LDH??,and treatment information?radiotherapy method,radiation dose,treatment mode?.We follow up the treatment efficacy,time,location of recurrence and metastasis,time to progression and death,and cardiac AEs 1 month after treatment.For eligible patients,the heart,pericardium and pulmonary artery were delineated in accordance with RTOG Atlases for Organs at Risk in Thoracic Radiation Therapy.Dosimetric parameters?Maximum dose,Mean dose?Dmean?,V5-V65,etc.?were extracted from dose-volume histogram.We analyze the correlation between dosimetry parameters of cardiac,pericardial and pulmonary artery and cardiac AEs as well as peripheral blood immune parameters.We also analyze their effect on survival.Kaplan-Meier method was used to calculate cumulative survival rate,and Log-rank test was used for comparison between groups.Cox proportional hazard regression model was used to perform multiparameter and multifactor analysis to determine independent predictors of survival.Results:A total of 94 patients with LA-NSCLC were included in this study.The median age was 62 years?range 41-87 years?,79%were male,58%were squamous cell carcinoma,and 37%of patients received concurrent chemoradiotherapy.The doses of radiotherapy range 60-72Gy/30-36 times.The median follow-up time was 26.2 months?range 7-76.5 months?.Among all patients,the objective response rate was 52.13%,the regional recurrence rates at 1 and 2 years were 22.3%and 24.5%,and the distant metastasis rates at 1 and 2 years were 33%.The median disease-free progression time?PFS?was 10.5 months?95%confidence interval?CI?:7.6-13.4 months?,and the median overall survival time?OS?was 19.6 months?95%CI:12.1-27.2 months?.One month after radiotherapy,cardiac AEs occurred in 25 patients,22 of which were grade 1?23.4%?,3 of which were grade 2?3.2%?,and no grade?3 cardiac AEs occurred.In all patients,the immunoinflammatory indexes NLR,LMR,and PLR were significantly different between before and after radiotherapy?p<0.001?.In the subgroup,the post-treatment LMR(LMR_post)of the group with heart-related adverse event?HRAE?was significantly lower than that of the group without heart-related AEs?NHRAE?.The pre-treatment LDH(LDH_pre)of the HRAE group was significantly higher than that of the NHRAE group.There were no statistical differences between the HRAE and NHRAE group in gross tumor volume,clinical target volume,planning target volume as well as volume and dose volume parameters?V5-V65?of cardiac,pericardial and pulmonary artery?p>0.05?.There was no correlation between the dosimetric parameters of cardiac,pericardial,and pulmonary artery with immunoinflammatory indicators and recent cardiac AEs.Univariate analysis showed pathological types,immunoinflammatory indicators(NLR_pre/post,PLR_pre/post,LMR_pre),cardiac indicators(CK_pre/post,CK-MB_pre),Dmean,V5 and V20 for both lungs,PC_V55-V65,PA_V55-V65)were related to OS?p<0.1?,but the recent cardiac AEs and cardiac dosimetry parameters were not related to OS.Multivariate analysis showed that pathological type,CK-MB_pre,NLR_post,PC_V60,PC_V65,and PA_V6565 were independent predictors of OS?p<0.05?.Conclusion:Radiation dosimetry parameters of heart,pericardium and pulmonary artery in patients with LA-NSCLC who received radical chemoradiotherapy did not affect the changes of patients'immune function parameters.Immunoinflammatory indicators NLR_postost and cardiac indicators CK-MB_pre,pericardial and pulmonary arterial dosimetry parameters(PC_V60-65,PA_V65)are associated with poor prognostic survival and are not connected with recent cardiac adverse events.