| Objective: The standard treatment for unresectable locally advanced non-small cell lung cancer(LA-NSCLC)is radical chemoradiotherapy,which is divided into involved field radiotherapy(IFRT)and elective nodal irradiation(ENI)according to the different irradiation field of mediastinal lymphatic drainage region(LDR).ENI may increase local control,but also excessively kill immune cells in LDR,weaken the innate or adaptive antitumor immunity and affect survival.This study aimed to evaluate the effects of irradiation field and dosimetric parameters of mediastinal LDR in patients with LA-NSCLC who received radical radiotherapy on immunoinflammatory biomarkers,local control and survival.Methods: In this retrospective study,we enrolled patients with LA-NSCLC who underwent radical chemoradiotherapy(?60Gy)at Shengjing Hospital,China Medical University from Dec,2013 to Jun,2019.Clinicopathological information,target's dosimetric parameters,immunoinflammatory biomarkers,irradiation field of mediastinal LDR,and follow-up data were collected.The mediastinal expanded LDR volume(MV)was contoured according to the atlas for mediastinal lymph nodes in lung cancer,the residual MV(RMV)was formed by subtracting the gross tumor volume(GTV)from MV,and dose-volume histograms were generated.Factors affecting immunoinflammatory biomarkers,local control and dosimetric parameters were analyzed statistically.KaplanMeier and Cox proportional hazards regression model was used to identify the prognostic factors.The optimal cutoff points of continuous variables were determined by Youden index in receiver operating characteristic(ROC)analysis.Results: Of the 88 patients with LA-NSCLC,radiation dose ranged from 60 to 74 Gy in 30–37 fractions.53(60.2%)patients had squamous cell carcinoma,34(38.6%)patients received concurrent chemoradiotherapy,40(45.5%)and 48(54.5%)patients received ENI and IFRT,respectively.The local regional recurrence rates of ENI and IFRT were 27.5% and 39.6%,the distant metastasis rates were 45% and 33.3%,respectively,P>0.05.Median PFS was 10.5 months and median OS was 20.9 months.The 1,2,and 3 year OS rates were 65%,45%,and 31%,respectively.The peripheral blood neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were increased,while the absolute lymphocyte count(ALC)and lymphocyte-to-monocyte ratio(LMR)were decreased significantly after radiotherapy,P<0.05,regardless of the irradiation field of mediastinal LDR.NLRpost and PLRpost in non-response group(NR)were higher than those in response group(R),and LMRpost was lower than that in R group,P<0.05.Univariate analysis showed that pathological types,mediastinal LDR irradiation field,LMRpre,PLRpre,NLRpost,lung V5 and V20,MVV5–V65 and RMVV5–V65 were related to OS(P<0.05).Multivariate analysis showed that mediastinal LDR irradiation field,PLRpre,NLRpost,MVV65,and RMVV65 were independent predictors for OS.ENI,PLRpre>123.76,NLRpost>3.67,MVV65>7.5%,and RMVV65>4% were all associated with poor survival.Conclusion: In patients with LA-NSCLC receiving radical chemoradiotherapy,ENI didn't reduce peripheral blood immunoinflammatory biomarkers compared with IFRT.However,IFRT significantly improved survival and didn't increase the local control,although with relatively smaller irradiation field compared with ENI.High dose-volume irradiation of mediastinal expanded LDR(MVV65>7.5% and RMVV65>4%)and high immunoinflammatory biomarkers(NLRpost>3.67 and PLRpre>123.76)were associated with poor survival,it can be used as predictors of poor survival in LA-NSCLC patients. |
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