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Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis.
Psallidas, Ioannis; Kanellakis, Nikolaos I; Gerry, Stephen; Thézénas, Marie Laëtitia; Charles, Philip D; Samsonova, Anastasia; Schiller, Herbert B; Fischer, Roman; Asciak, Rachelle; Hallifax, Robert J; Mercer, Rachel; Dobson, Melissa; Dong, Tao; Pavord, Ian D; Collins, Gary S; Kessler, Benedikt M; Pass, Harvey I; Maskell, Nick; Stathopoulos, Georgios T; Rahman, Najib M.
  • Psallidas I; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
  • Kanellakis NI; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
  • Gerry S; Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
  • Thézénas ML; Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Charles PD; Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Samsonova A; Bioinformatics Core, Department of Oncology, University of Oxford, Oxford, UK; Institute of Translational Biomedicine, St Petersburg State University, St Petersburg, Russia.
  • Schiller HB; Comprehensive Pneumology Center and Institute for Lung Biology and Disease, University Hospital, Ludwig-Maximilian University, Munich, Bavaria, Germany; Helmholtz Center Munich, Member of the German Center for Lung Research, Munich, Bavaria, Germany.
  • Fischer R; Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Asciak R; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
  • Hallifax RJ; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
  • Mercer R; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
  • Dobson M; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dong T; Centre for Translational Immunology, CAMS-Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Pavord ID; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Collins GS; Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
  • Kessler BM; Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Pass HI; Department of Cardiothoracic Surgery New York University Langone Medical Center, New York, NY, USA.
  • Maskell N; Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK.
  • Stathopoulos GT; Comprehensive Pneumology Center and Institute for Lung Biology and Disease, University Hospital, Ludwig-Maximilian University, Munich, Bavaria, Germany; Helmholtz Center Munich, Member of the German Center for Lung Research, Munich, Bavaria, Germany; Laboratory for Molecular Respiratory Carcinogenes
  • Rahman NM; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Respiratory Trials Unit, Nuffield Departme
Lancet Oncol ; 19(7): 930-939, 2018 07.
Article en En | MEDLINE | ID: mdl-29908990
ABSTRACT

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.

FUNDING:

European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Causas de Muerte / Derrame Pleural Maligno / Pleurodesia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2018 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Causas de Muerte / Derrame Pleural Maligno / Pleurodesia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2018 Tipo del documento: Article