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BACKGROUND: Most patients with malignant pleural mesothelioma (MPM) present with malignant pleural effusion (MPE). There is in vitro evidence that MPE may not be a simple bystander of malignancy, but potentially has biological properties improving cancer cell survival and promoting cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact on survival. RESEARCH QUESTION: Is there an association between pleural fluid exposure and survival in MPM? STUDY DESIGN AND METHODS: Data on 761 patients diagnosed with MPM between 2008-2018 were collected from patient medical records in 3 UK pleural units. Data included factors previously identified as influencing prognosis in MPM. Medical imaging was reviewed for presence, size and duration of pleural effusion. Time-dependent covariate analysis of pleural fluid exposure and survival (model included weight loss, serum albumin, Hb, MPM subtype, performance status, chemotherapy, age), and multivariable cox regression analysis of pleurodesis and survival were conducted. RESULTS: Median overall survival was 278 days (IQR 127-505, 95% CI 253-301). Pleural fluid exposure duration showed no association with survival (HR 1.0, 95% CI 1.0-1.0). Median survival was 473, 378 and 258 days with complete, partial, and no pleurodesis (p 0.008). INTERPRETATION: Pleurodesis success appears to be associated with improved survival, however it is unclear whether duration of MPM exposure to pleural fluid is associated with survival within the limitations of this retrospective study. Future prospective studies are required to assess this potentially important mechanism.

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