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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-11062021-132043
Document
Author
Full name
Fernando Conrado Abrão
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Negri, Elnara Márcia (President)
Capelozzi, Vera Luiza
Gróss, Jefferson Luiz
Teixeira, Lisete Ribeiro
Title in Portuguese
Desfecho clínico em pacientes com derrame pleural neoplásico
Keywords in Portuguese
Cuidados paliativos
Derrame pleural maligno
Fatores de risco
Neoplasias pulmonares
Recorrência
Abstract in Portuguese
A proposta foi reconhecer os fatores de risco de recorrência do derrame pleural maligno (DPM) em pacientes com derrame pleural maligno (DPM) sintomático. Métodos: Através de banco de dados prospectivamente organizado de casos com derrame pleural tratados em uma única instituição, foram realizadas duas análises separadamente. A primeira análise incluiu apenas pacientes com câncer de pulmão e a segunda análise contemplou pacientes portadores de câncer de diversos tipos sítios primários. Todos os pacientes com DPM submetidos a procedimentos paliativos foram incluídos em um estudo prospectivo. Em relação a primeira análise, o grupo I continha pacientes com recidiva pleural e o grupo II sem recidiva pleural. Os fatores prognósticos para recorrência pleural foram identificados por análise univariada, utilizando o teste exato de Fisher para variáveis categóricas e o teste t de Student para variáveis quantitativas. Posteriormente, as variáveis significativas foram inseridas em uma análise de regressão logística multivariável (com P < 0,05 considerado significativo). A curva ROC (receiver operating characteristics) determinou os pontos de corte para variáveis contínuas. Em relação a segunda análise, analisamos fatores prognósticos para recorrência pleural. Esta identificação foi feita através de análise univariada pelo método de Kaplan-Meier e o teste logrank foi utilizado para comparação entre as curvas. Modelos de regressão de Cox univariados e múltiplos foram utilizados para avaliar o risco (Hazard Risk ) de recorrência. A curva ROC (receiver operating characteristics) determinou os pontos de corte para variáveis contínuas. Resultados: em relação a nossa primeira análise, 82 pacientes foram incluídos na análise. Havia 15 pacientes (18,3%) no grupo I e 67 pacientes (81,7%) no grupo II. A análise univariada dos fatores que afetam a recorrência pós-operatória foi: concentração de adenosina desaminase no líquido pleural < 16 mg / dL (p = 0,04), concentração de albumina no líquido pleural < 2,4 mg / dL (p = 0,03), administração de quimioterapia paliativa de segunda linha ( p = 0,018) e tipo de procedimento [toracocentese] (p = 0,023). Na análise multivariável, apenas o tipo de procedimento (toracocentese) (p = 0,031) foi identificado como preditor independente de recorrência. Por outro lado, quando analisamos nosso segundo subgrupo de pacientes (pacientes de diversos sítios primários), 288 pacientes foram incluídos na amostra. A sobrevida livre de recorrência foi de 76,6% em 6 meses e 73,3% aos 12 meses. Fatores positivos na análise univariada associados à recorrência pós-operatória foram: concentração de linfócitos e plaquetas no sangue periférico, procedimento pleural, linhas de quimioterapia realizadas e número de metástases. Os fatores independentes para sobrevida livre de recorrência foram procedimento pleural e linhas de quimioterapia. Pacientes submetidos à pleurodese apresentaram fator de proteção para recidiva, com HR = 0,34 (IC 95%,0,15-0,74, p = 0,007). Por outro lado, os pacientes submetidos à 1ª e 2ª linha de TC paliativa apresentaram, respectivamente, um risco de recorrência maior, HR = 2,81 (IC 95%, 1,10-7,28, p = 0,034) e HR = 3,23 (IC 95%, 1,33-7,84, p = 0,010). Concluímos que em nosso estudo, os pacientes que receberam a primeira ou a segunda linha de tratamento sistêmico têm maior risco de recorrência do DPM quando comparados aos pacientes que foram submetidos ao tratamento pleural antes de iniciar o tratamento sistêmico. O uso da toracocentese esteve associado com recorrência do DPM quando comparado a outros métodos de tratamento cirúrgico
Title in English
Clinical outcome in patients with neoplastic pleural effusion
Keywords in English
Palliative care, Lung neoplasms
Pleural effusion malignant
Recurrence
Risk factors
Abstract in English
Background: It is known that malignant pleural effusion (MPE) recurs rapidly, in a considerable number of patients. However, some patients do not have MPE recurrence. Since MPE is associated with an average survival of 4-7 months, accurate prediction of prognosis may help recognize patients at higher risk of pleural recurrence, aiming to individualize more intensive treatment strategies.Methods: Through a prospectively organized database of cases with pleural effusion treated in a single institution, two applied analyzes were performed. The first analysis included only patients with non-small cell lung cancer (NSCLC) submitted to pleural palliative procedures. Group I contained patients who had pleural recurrence, and Group II with no pleural recurrence. Prognostic factors for pleural recurrence were identified by univariable analysis, using Fisher's exact test for categorical variables and Student's t test for quantitative variables. Afterwards the significant variables were entered into a multivariable logistic regression analysis (with p < 0.05 considered significant). Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables. Regarding second analysis, prognostic factors for pleural recurrence were identified by univariable analysis using Kaplan-Meier method and the log-rank test was used for the comparison between the curves. Univariate and multiple Cox regression models were used to evaluate the risk (HR) of recurrence. Receiver operating characteristics (ROC) analysis also determined the cutoff points for continuous variables.Results: About our first analysis, a total of 82 patients were included in the analysis. There were 15 patients (18.3%) in Group I and 67 patients (81.7%) in Group II. Univariable analysis regarding factors affecting postoperative recurrence was: adenosine deaminase concentration in pleural fluid < 16 mg/dl (p= 0.04), albumin concentration in pleural fluid < 2.4 mg/dl (p= 0.03), administration of second-line palliative chemotherapy (p=0.018) and type of procedure [therapeutic pleural aspiration (TPA)] (p=0.023). At the multivariable analysis, only the type of procedure (TPA) (P=0.031) was identified as independent predictor of recurrence. Regarding our second analysis, A total of 288 patients were included. Recurrence-free survival was of 76.6% at 6 months and 73.3% at 12 months. Univariable analysis regarding factors affecting postoperative recurrence was: lymphocytes, platelets, pleural procedure, chemotherapy lines and number of metastases. The independent factors for recurrence-free survival were pleural procedure and chemotherapy lines. Patients who were submitted to pleurodesis had a protective factor for recurrence, with an HR =0.34 (95% CI, 0.15-0.74, p=0.007). On the other hand, patients submitted to the 1st and 2nd line of palliative CT had, respectively, an HR risk = 2.81 (95% CI, 1.10-7.28, p=0.034) and HR =3.23 (95% CI, 1.33-7.84, p=0.010). Conclusions :patients receiving the first or second line of systemic treatment have a higher risk of MPE recurrence when compared to patients who underwent MPE treatment before starting the systemic treatment. The definitive treatment of MPE, such as pleurodesis, was associated with a lower risk of MPE recurrence
 
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