Journal article
Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis
- Abstract:
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Background: The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival.
Methods: In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation.
Findings: 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72–0·83] for internal validation and 0·89 [0·84–0·93] for external validation of the clinical PROMISE score).
Interpretation: To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 669.6KB, Terms of use)
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- Publisher copy:
- 10.1016/S1470-2045(18)30294-8
Authors
- Funding agency for:
- Hallifax, R
- Grant:
- MR/L017091/1
- Funding agency for:
- Kanellakis, N
- Pavord, I
- Grant:
- STRTF 2015-9508
- RESPIRE2 – 2015–7160
- *Grant Number Example*
- Grant:
- *Grant Number Example*
- Publisher:
- Elsevier
- Journal:
- Lancet Oncology More from this journal
- Volume:
- 19
- Issue:
- 7
- Pages:
- 930-939
- Publication date:
- 2018-06-13
- Acceptance date:
- 2018-04-11
- DOI:
- EISSN:
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1474-5488
- ISSN:
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1470-2045
- Pubs id:
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pubs:836582
- UUID:
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uuid:c9eff614-3804-4c71-9f82-d8654d82c874
- Local pid:
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pubs:836582
- Source identifiers:
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836582
- Deposit date:
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2018-04-16
Terms of use
- Copyright holder:
- Elsevier Ltd
- Copyright date:
- 2018
- Notes:
- © 2018 Elsevier Ltd. All rights reserved. This is the author accepted manuscript following peer review version of the article. The final version is available online from Elsevier at: 10.1016/S1470-2045(18)30294-8
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