Efficacy And Prognostic Analysis Of Different Pleural Interventions On Patients With Malignant Pleural Effusion

Backgroud Malignant pleural effusion(MPE)is one of the common tumor complications,which is easy to cause repeated dyspnea,chest tightness,cough and other discomfort,and seriously affect the quality of life.Currently,the treatment for MPE is palliative,and the principle is to timely relieve symptoms,improve quality of life,and reduce pleural interventions in the remaining survival period.As the most commonly used treatment option,thoracocentesis has drawbacks such as high recurrence rate,heavy burden of symptoms,and significantly increased risk of readmission.Therefore,foreign guidelines recommend that symptomatic MPE patients should receive definitive pleural interventions as soon as possible,such as pleurodesis or indwelling pleural catheter(IPC).In addition,tumor targeted therapy and immunotherapy can significantly improve the anti-tumor effect and also control the progress of MPE,but effective systemic anti-tumor therapy may reduce the need for early implementation of definitive pleural interventions.Under the background of systemic anti-tumor therapy,there are few studies in China comparing the efficacy and survival of simple drainage and intrapleural injection in the treatment of newly diagnosed patients with symptomatic MPE,and there is no consensus on the best intrapleural injection regimen for the treatment of MPE.Objective The purpose of this study is to explore:(1)whether there is a difference in the efficacy and survival outcome of patients with symptomatic MPE treated with simple drainage and intrapleural injection,and analyze the prognostic factors affecting survival;(2)whether there are differences in the efficacy and survival outcomes of different intrapleural injection regimens for patients with lung cancer-associated MPE,and analyze the prognostic factors affecting survival of patients with lung cancer-associated MPE.Methods Part I:This is a single-center retrospective cohort study.Collect the information of MPE patients who were hospitalized in the Department of Respiratory and Critical Care of the Second Affiliated Hospital of the Air Force Military Medical University from January 1,2016 to December 30,2021,and who met the inclusion and exclusion criteria.Obtain the general demographic characteristics,clinical data and outcome indicators through the medical record system and telephone follow-up.The follow-up deadline is June 30,2022.The patients were divided into simple drainage group and intrapleural injection group.1:1 propensity score matching(PSM)was used to adjust the difference of baseline indicators between the two groups.The MPE control rate,the improvement rate of Karnofsky performance score(KPS)and the number of re-interventions on ipsilateral MPE were compared after the first pleural intervention in the two groups.Kaplan-Meier method was used to compare the time from initial thoracentesis to ipsilateral MPE recurrence requiring pleural intervention within 6 months,pleural progression-free survival(PPFS)and overall survival(OS).Multivariate Cox proportional risk regression model was used to verify whether there was independent correlation between pleural interventions and OS,and to explore independent prognostic factors affecting OS of MPE patients.Part II:The patients who were diagnosed as lung cancer with MPE in the first part and were treated with intrapleural injection were selected as the study subjects.According to the different intrapleural injection regimens,the patients were divided into cisplatin group,Sapylin combined with cisplatin group,and anti-angiogenic drugs group,which were recorded as group A,group B,and group C.The outcome indicators are the same as the part I.The adjusted odds ratio(OR)was calculated by multivariate logistic regression,and the adjusted risk ratio(HR)was calculated by multivariate Cox regression,the differences of outcome indicators among three groups were compared,and to explore independent prognostic factors affecting OS of patients with lung cancer-associated MPE.Results Part I:1.A total of 310 patients were included,including 92 patients in the simple drainage group and 218 patients in the intrapleural injection group.The median follow-up time of the whole group was 21 months(95% CI 18.0-24.0),and 29 cases(9.35%)failed to be followed up.After PSM,there were 79 patients in the drainage group and 79 patients in the intrapleural injection group.The baseline balance between the groups was comparable.2.The 1-month MPE control rate(88.61% vs.70.89%,P=0.006),3-month MPE control rate(83.54% vs.69.62%,P=0.039),and 1-month KPS improvement rate(74.68%vs.55.70%,P=0.012)in the intrapleural injection group were significantly higher than those of the simple drainage group.There was no statistical difference in other indicators.3.There was no statistical difference in the median PPFS(16 vs.13 months,P=0.178)and median OS(25 vs.21 months,P=0.08)between the simple drainage group and the intrapleural injection group.There was no independent correlation between pleural interventions and OS(HR=1.51,P=0.078).Smoking ≥ 20 pack years(HR=2.32,P=0.001),peripheral blood C-reactive protein(CRP)>5mg/L(HR=1.93,P=0.006),and MPE progression after the first pleural intervention(HR=1.70,P=0.025)were independent prognostic factors for poor OS.Complete systemic chemotherapy(HR=0.15,P<0.001),targeted therapy(HR=0.08,P<0.001),and combined therapy(HR=0.06,P<0.001)after the diagnosis of MPE are independently related to better OS.Part II:1.There were 201 patients in total,including 48,120 and 33 patients in group A,B and C,respectively.The median follow-up time of the whole group was 19 months(95%CI,15.4-22.6),and 20 cases(9.95%)were lost to follow-up(9.95%).2.The 1-month MPE control rate in group A,B and C was 72.92%,90.83% and69.70%,respectively.The 3-month MPE control rate was 56.25%,89.17% and 66.67%,respectively.The MPE control rate in group B was the highest.There was no statistical difference in the improvement rate of KPS in 1 month and 3 months among the three groups.The risk of MPE progression in 6 months in group B was significantly lower than that in group A(adjusted HR=0.24,P<0.001).The proportion of patients in group B(76.67%)who did not intervene on ipsilateral MPE was significantly higher than that in group A(45.83%)and group C(51.52%),and the proportion of patients in group B(1.67%)who intervened more than three times was significantly lower than that in group A(10.42%)and group C(21.21%).3.The median PPFS of group A,B,and C was 7,14,and 9 months,respectively.There was no statistical difference in PPFS among three groups(Logrank P=0.072).Taking Group A as a reference,there was no statistical difference in PPFS between Group B(adjusted HR=0.677,P=0.240)and Group C(adjusted HR=2.59,P=0.076).The median OS of group A,B,and C was 24,22,and 21 months,respectively.There was no statistical difference in OS between groups(Logrank P=0.828).Taking Group A as a reference,there was no statistical difference in OS between Group B(adjusted HR=0.94,P=0.819)and Group C(adjusted HR=1.01,P=0.974).Liver metastasis(HR=3.37,P=0.001),peripheral blood CRP>5mg/L(HR=1.69,P=0.017),presence of hypoalbuminemia(HR=1.74,P=0.015),and MPE progression after the first pleural intervention(HR=1.84,P=0.005)were independent prognostic factors for poor OS.Compared with small cell lung cancer patients with MPE,patients with adenocarcinoma(HR=0.48,95% CI 0.27-0.87,P=0.016)had better OS.After the diagnosis of MPE,the completion of systemic chemotherapy(HR=0.22,P<0.001),targeted therapy(HR=0.13,P<0.001),combined therapy(HR=0.17,P<0.001)were independently related better OS.Conclusion1.For newly diagnosed patients with symptomatic MPE,intrapleural injection of anti-tumor drugs can reduce the risk of fluid accumulation in the short term,improve the physical function and improve the quality of life.There may be no independent relationship between the first pleural intervention and survival outcome of newly diagnosed MPE patients.Smoking index,peripheral blood CRP level,MPE progression,and active anti-tumor therapy are independent prognostic factors for OS.2.For the newly diagnosed MPE patients with lung cancer,intrapleural injection of Sapylin combined with cisplatin has advantages in controlling the progress of effusion and reducing the number of subsequent re-interventions in the ipsilateral MPE.There may be no independent relationship between the first intrapleural injection regimens and the prognosis of MPE patients associated with lung cancer.Liver metastasis,peripheral blood CRP level,albumin level,MPE progression,pathological types of lung cancer,and active anti-tumor treatment are independent prognostic factors of OS.