| ObjectiveRecently,Immune Checkpoint Inhibitors is a mainstay approach for treating multiple cancers.Many clinical studies at home and abroad have confirmed that ICI can improve the prognosis of patients and bring dawn to them.NSCLC is a common pathological type of lung cancer.With more and more ICI being approved for lung cancer adaptation in China,a variety of ICIs such as Pembrolizumab and Sintilimab have been recommended as front-line therapy for advanced NSCLC.ICIs will be increasingly widely used in clinic,providing a better choice for cancer patients than existing chemotherapy and radiotherapy,and more patients will benefit from it.However,the immune checkpoint inhibitor can over-activate the immune system and damage the tissues and organs of its own host,which is called irAEs.CIP is one of the most common adverse events.The total incidence of CIP and the incidence of severe CIP in patients with NSCLC are higher than those in other cancer patients.At present,the mechanism,predictive factors and clinical features of CIP have not been clarified.Also,there are limited data on the outcomes and prognostic utility of biomarkers associated with CIP.Therefore,this study intends to conduct a retrospective analysis of patients diagnosed with CIP during hospitalization in our hospital based on the demographic information,medication history,disease history and other indicators of patients,to explore the predictive factors of CIP,analyze the correlation between various factors and/or comprehensive factors and the occurrence of CIP,and explore the predictive factors leading to CIP.MethodWe retrospectively studied 117 patients who developed CIP while receiving ICI therapy at the department of Internal Medicine-Oncology from January 2018 to June 2022.Patients with clinically diagnosed CIP were included in the case group,and patients without CIP or other irAEs were included in the control group in a ratio of 1:1.We obtained age,sex,body index,smoking history,medical history of respiratory system deasese,TMN stage and laboratory tests,interleukin,tumor necrosis factor,interferon level and other clinical test included.We also obtained the result of Radiography,course of ICI,and characteristic during CIP.Among them,the CIP group collected the baseline(before receiving the ICIs for the first time)and the record of the occurrence of CIP,while the control group collected the examination results before the last ICI therapy within the baseline and the study time.ResultWe conducted a retrospective analysis of 117 patients with CIP(CIP group)and 117 patients without CIP or other irAEs(Control group).Adenocarcinoma is the most common tumor pathological type among NSCLC patients receiving ICI treatment.According to the TMN stage,most patients are classified as stage Ⅲ to stage Ⅳ Most patients receive PD-1 inhibitor treatment,including 114 patients in CIP group and 113 patients in control group.Other patients receive PD-L1 inhibitor treatment.The levels of IL-8,IL-17A,and hsCRP in patients with NSCLC after treatment with ICIs in both the CIP group and the control group showed significant differences from baseline.Elevated levels of multiple cytokines are significantly associated with CIP in patients with NSCLC.Binary logistic regression analysis showed that tumor pathological type(OR:2.769,95%CI:1.056-7.264;P=0.038),ICI monotherapy(OR:17.204,95%CI:1.716-172.517,P=0.016),were significantly relative to CIP.Based on severity,patients in the CIP group can be divided into 54 cases of mild CIP and 63 cases of severe CIP.COX proportional risk regression model showed that severe CIP,high LDH levels during CIP,low AMC levels,and low ALB levels were significantly associated with poor overall survival in CIP(P<0.05).Single factor analysis showed that there were significant differences in the levels of IL-10,NLR,LDH,and ALB during CIP between mild and severe CIP(P<0.05).The results of binary logistic regression analysis suggest that high levels of IL-10 and LDH during CIP are risk factors for severe CIP.12 patients(10.3%)experienced co-occurred irAEs while undergoing CIP,of which the most common complication was ICI-myocarditis in 4 patients(3.4%).The proportion of patients with severe CIP in co-occurred irAEs group was significantly higher than that in the non-combined group(91.7%vs 49.5%,P=0.014),and the overall survival of patients in this group was lower.Patients with IL-8≥ 35.655 and LDH≥ 307.5 at CIP may have potential for co-occurred irAEs.According to onset time of CIP,there were 58 cases of early-onset CIP and 59 cases of late-onset CIP.Compared with late-onset CIP,early onset CIP has a higher incidence of severe CIP(63.8%vs 44.1%,P=0.032)and a poorer prognosis(HR=12.89,95%CI:4.34-38.25,P=0.0015).Baseline IL-17A levels may be an independent predictor of early-onset and late-onset CIP.ConclusionSquamous cell carcinoma,and ICI monotherapy are risk factors for the occurrence of CIP in NSCLC patients.After ICIs treatment,the levels of IL-8,IL-17A,and hsCRP in NSCLC patients decreased.The average value of IL-8 will increased in both CIP group and control group after treatment;the IL-17A level in the CIP group increased after treatment,while the control group decreased;The level of hsCRPS in CIP group increased during CIP,while the control group decreased after ICI treatment.PLT,ALB,and LDH were associated with overall survival during CIP.NSCLC patients with suspected CIP and high levels of IL-10 and LDH should be alert to severe CIP.Patients with high levels of IL-8 and LDH during CIP may be a sign of other irAEs.Baseline IL-17A levels may be an independent risk factor of early-onset and lateonset CIP.This study found that the imaging manifestations of CIP are mainly patchy shadows,and a clear diagnosis needs to be made based on the patient’s medication history and exposure history. |
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