Efficacy And Adverse Reactions Of Intrathoracic Therapy In Patients With Non-small Cell Lung Cancer And Malignant Pleural Effusion In Real World

ObjectiveTo evaluate the efficacy and adverse reactions of intrathoracic treatments for non-small cell lung cancer(NSCLC)patients combined with malignant pleural effusion(MPE)in the real world.Materials and MethodsThe medical records of NSCLC patients with MPE who were diagnosed in four hospitals in Shandong Province between October 2014 and December 2019 were retrieved,and patients were selected according to the inclusion and exclusion criteria.The follow-up ended in October 2020.The baseline characteristics of patients were collected with the first diagnosis of MPE as the baseline date.During the follow-up period,intrathoracic and systemic treatment regimens were collected,and the pleural effusion and systemic efficacy was analyzed according to the pleural effusion evaluation criteria and response evaluation criteria for solid tumors(RECTST)version 1.1.According to the intrathoracic drugs,it is divided into 3 groups:erythromycin group(EG,intrathoracic treatment with drugs and erythromycin),intrathoracic treatment group(ITG,intrathoracic treatment with drugs),control group(CG,no drug treatment in the pleural cavity or puncture and drainage only).Systemic treatment is based on the National Comprehensive Cancer Network guideline.The main study endpoint is median overall survival(mOS),and the secondary study endpoint is 6 weeks,12 weeks pleural effusion-objective response rate(PE-ORR)and systemic objective response rate(S-ORR).Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events Version 4.0 and World Health Organization Verbal Rating Scale.Results1.643 patients were retrieved,of which 285 patients were included.81.1%of patients received intrathoracic treatment,of which 9 were asymptomatic;32 of 45 patients with atelectasis received intrathoracic treatment,and no patients received talc pleurodesis or long-term catheter drainage.The mOS of all patients was 21 months.The mOS of EG,ITG,and CG patients were 20,22,and 19 months,respectively(P=0.744).The 6-week and 12-week PE-ORR of EG was slightly higher than that of ITG and CG,but there was no statistical difference(75.8%vs.62.4%vs.71.7%,P=0.217;76.7%vs.70.5%vs.72.7%,P=0.776).2.The patients were divided into targeted and non-targeted treatment group according to whether there were targeted drugs in the systemic treatment regimen.The mOS of EG,ITG and CG patients in the targeted treatment group were 52,30 and 32 months,respectively(P=0.215).The mOS of three groups in the non-targeted treatment group was 13,13 and 7 months,respectively(P=0.054).EG and ITG were combined into an intrathoracic administration group(IAG).In the targeted treatment group,IAG patients did not achieve longer mOS compared with the CG(31 vs.32 months,P=0.660).In the non-targeted treatment group,the mOS of IAG was significantly better than that of the CG(13 vs.7 months,P=0.018).Among patients who only received chemotherapy as systemic therapy,the mOS of IAG was also significantly better than that of the CG(12 vs.6 months,P=0.034).3.The distribution of tumor burden was quantitatively expressed as the ratio of carcinoembryonic antigen in pleural effusion(PE-CEA)to blood carcinoembryonic antigen in blood(B-CEA).PE-CEA:B-CEA ratio>1 indicates that the tumor burden is mainly distributed in the pleura,and PE-CEA:B-CEA ratio ≤1 indicates that the tumor burden is mainly distributed in other parts than the pleura.In the IAG of targeted treatment group,the mOS of patients with PE-CEA:B-CEA ratio>1 and CEA ratio≤1 was 36 and 21 months,respectively(P=0.510).Among the IAG of non-targeted treatment group,patients with PE-CEA:B-CEA ratio>1 had significantly better mOS than those with CEA ratio≤1(13 vs.4months,P=0.015).Among patients who only received chemotherapy as systemic therapy,IAG patients with PE-CEA:B-CEA ratio>1 had better mOS than that of control group,and IAG patients with CEA ratio≤1 with had the worst mOS(12 vs.6 vs.4 months,P=0.032).In a pairwise comparison,the mOS of IAG patients with PE-CEA:B-CEA ratio>1 was better than that of patients with CEA ratio ≤1 and that of control group patients(12 vs.4 months,P=0.021;12 vs.6 months,P=0.059),but there was no statistical difference in mOS between IAG patients with CEA ratio ≤1 and control group patients(4 vs.6 months,P=0.442).4.The incidence of chest pain in EG patients was higher than that in ITG and CG,but there was no significant difference in systemic adverse reactions among the three groups.Conclusions1.In China,the actual situation of intrathoracic treatment of NSCLC patients with MPE is very different from the guidelines,and most patients receive intrapleural treatment.2.NSCLC patients with MPE who did not receive systemic targeted treatment had significantly prolonged survival time after intrathoracic therapy;patients who received systemic targeted therapy had no benefit in intrathoracic therapy.3.Intrathoracic therapy prolongs survival time in MPE patients whose tumor burden is mainly distributed in the pleura,and the PE-CEA:B-CEA ratio can predict the efficacy of intrathoracic therapy.4.Intrapleural therapy did not increase systemic adverse reactions in MPE patients.