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Psallidas, I.* ; Kanellakis, N.I.* ; Gerry, S.* ; Thézénas, M.L.* ; Charles, P.D.* ; Samsonova, A.* ; Schiller, H. B. ; Fischer, R.* ; Asciak, R.* ; Hallifax, R.J.* ; Mercer, R.* ; Dobson, M.* ; Dong, T.* ; Pavord, I.D.* ; Collins, G.S.* ; Kessler, B.M.* ; Pass, H.I.* ; Maskell, N.* ; Stathopoulos, G.T. ; Rahman, N.M.*

Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): A multicohort analysis.

Lancet Oncol. 19, 930-939 (2018)
DOI Verlagsversion bestellen
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Randomized Controlled-trial; Tissue Inhibitor; Chest Tube; In-vitro; Cancer; Management; Cells; Mesothelioma; Expression; Prognosis
ISSN (print) / ISBN 1470-2045
e-ISSN 1474-5488
Zeitschrift Lancet Oncology, The
Quellenangaben Band: 19, Heft: 7, Seiten: 930-939 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 360 Park Ave South, New York, Ny 10010-1710 Usa
Begutachtungsstatus Peer reviewed