The Association Between Pleural Fluid Exposure and Survival in Pleural Mesothelioma

Our plain-English summary of The Association Between Pleural Fluid Exposure and Survival in Pleural Mesothelioma, by R. Asciak, N.I. Kanellakis, A. Bibby, et al (Chest, 2021).

The study

• Authors: R. Asciak, N.I. Kanellakis, A. Bibby, A. Kidd, S. Gerry, R. Mercer, N. Maskell, K.G. Blyth, P. Fsadni, S. Montefort, I. Psallidas, N.M. Rahman
• Journal: Chest
• Published: 2021;160(5):1925-1933
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Most patients with malignant pleural mesothelioma (MPM) seek treatment with malignant pleural effusion (MPE). In vitro evidence suggests that MPE may not be a simple bystander of malignancy, but rather potentially has biological properties that improve cancer cell survival and promote cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact survival.

Research Question: Is there an association between pleural fluid exposure and survival in MPM?

Study Design And Methods: Data from 761 patients who received a diagnosis of MPM between 2008 and 2018 were collected from patient medical records in three 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, hemoglobin, MPM subtype, performance status, chemotherapy, and age) and multivariate Cox regression analysis of pleurodesis and survival were conducted.

Results: Median overall survival was 278 days (interquartile range, 127-505 days; 95% CI, 253-301 days). Pleural fluid exposure duration showed no association with survival (hazard ratio, 1.0; 95% CI, 1.0-1.0). Median survival was 473, 378, and 258 days with complete, partial, and no pleurodesis (P = .008).

Interpretation: Pleurodesis success seems 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.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective study reviewed medical records of 761 patients diagnosed with malignant pleural mesothelioma between 2008 and 2018 at three UK pleural units. The exposure studied was pleural fluid (malignant pleural effusion), not asbestos. The authors measured how many days fluid was present after diagnosis and whether pleurodesis (sealing of the pleural space) was achieved. Among the 683 patients who died, median survival was 278 days (95% CI 253-301). In an analysis adjusted for weight loss, serum albumin, hemoglobin, subtype, performance status, chemotherapy and age, time with fluid showed no significant relationship with survival (hazard ratio 1.000; 95% CI 1.000-1.000). Median survival was 473 days with complete pleurodesis (128 patients), 378 days with partial pleurodesis (107) and 258 days with none (99). Pleurodesis success remained significantly associated with longer survival after adjustment. Effusion size at diagnosis was not associated with survival. The authors concluded that pleurodesis success seems to be associated with improved survival. They also concluded it is unclear whether prolonged fluid exposure worsened survival. They noted that their final adjusted model dropped 85.9% of cases because of missing data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective cohort study based on existing medical records and imaging
• Who was studied: 761 patients diagnosed with malignant pleural mesothelioma (MPM) between January 8, 2008 and February 28, 2018 at three UK tertiary-referral pleural units (Glasgow, Bristol, Oxford); median age 73; 72% epithelioid, 10% biphasic, 18% sarcomatoid
• Exposure: Exposure to malignant pleural effusion (pleural fluid) after MPM diagnosis, measured as the number of days fluid was present on chest radiographs and ultrasound reports. Also studied were effusion presence and size at diagnosis, and pleurodesis success (complete, partial, none). Asbestos exposure was not studied.
• Main results:
  • Median overall survival for patients who died (n = 683) was 278 days (interquartile range 127-505; 95% CI 253-301)
  • In a time-dependent analysis adjusted for weight loss, albumin, hemoglobin, subtype, ECOG performance status, age and chemotherapy, duration of effusion showed no significant relationship with survival (HR 1.000; 95% CI 1.000-1.000)
  • Unadjusted median survival was 473 days with complete pleurodesis (n = 128), 378 days with partial pleurodesis (n = 107) and 258 days with no pleurodesis (n = 99); P less than .0001; HR 0.750 (95% CI 0.652-0.864). A further 143 patients had no effusion and 284 had inadequate data.
  • In multivariate Cox regression including weight loss, subtype, ECOG PS, hemoglobin, albumin, age and chemotherapy, pleurodesis success remained significantly associated with longer survival (P = .008)
  • Patients who received intrapleural talc (n = 194) had longer median survival than those who did not (n = 187): 481 vs 369 days; P = .002; HR 0.705 (95% CI 0.567-0.877)
  • Median survival was 321 vs 286 days for patients with and without effusion at diagnosis (P 0.237; HR 0.611; 95% CI 0.270-1.384), which was not statistically significant. Effusion size at diagnosis showed no association with survival among 740 analyzed patients (P = .456).
  • Among 227 chemotherapy patients analyzed, 104 of 167 (62.3%) with effusion at the start of chemotherapy and 37 of 60 (61.7%) without effusion responded (p = 1.0)
• The authors' conclusion: The authors concluded that pleurodesis success seems to be associated with improved survival in MPM. Given potential biases in this retrospective analysis, they also concluded it is unclear whether prolonged exposure to effusion worsened survival or chemotherapy response. They called for a prospective study.
• Limitations the authors state:
  • Fluid exposure before the date of diagnosis could not be determined
  • Chest radiographs were taken opportunistically, so some patients may have achieved pleurodesis earlier than detected
  • Small to moderate effusions were counted as exposure even if they were possibly too small to bathe the tumor
  • Pleural fluid cannot always be distinguished from pleural thickening on chest radiography
  • Stable disease after chemotherapy may not mean the tumor responded to chemotherapy
  • The final Cox regression model dropped 85.9% of cases because of missing values
  • Talc pleurodesis may be confounded by indication related to performance status, and the method of talc delivery was unknown
  • Data on duration of effusion throughout chemotherapy were not available

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Effusion, Prognosis, Performance Status, Chemotherapy, Pleurodesis, Median Overall Survival, Hazard Ratio.

Related studies

• Survival in patients with malignant pleural effusion undergoing talc pleurodesis — M. Hassan, R.M. Mercer, et al. (2019)
• Clinically important associations of pleurodesis success in malignant pleural effusion: Analysis of the TIME1 data set — R.M. Mercer, J. Macready, et al. (2020)
• Prognostic factors for survival after surgical palliation of malignant pleural effusion — J.E. Pilling, M.E. Dusmet, et al. (2010)
• Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single-centre experience — J. Leemans, C. Dooms, et al. (2018)
• Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma — B. Dozin, G. Carbotti, et al. (2021)
• MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial — C. Matthews, C. Freeman, et al. (2019)

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