Malignant pleural mesothelioma: recognising an unmet need
Student thesis: Doctoral Thesis
Introduction: Malignant Pleural Mesothelioma (MPM) is an incurable malignancy with severe symptoms. It is challenging to diagnose and with limited treatments. The studies described here aim to determine the diagnostic accuracy of four biomarkers in MPM, identify factors to aid prognosticating, and test the efficacy of a novel intervention, early specialist palliative care (SPC). Methods: In the biomarker study ELISA evaluated SMRP, Fibulin-3, Osteopontin and HMGB-1 concentrations in MPM patients. Regression analysis assessed the ability of a series of patient factors from a retrospective MPM patient cohort to predict prognosis. The RESPECT-Meso study was a randomised controlled trial assessing early SPC versus standard care in a 1:1 ratio on quality of life (QOL) in 174 MPM patients. Key findings: The biomarker study revealed effusion SMRP levels were significantly higher in MPM patients compared to benign and other malignant effusions (3170nM/L vs 210nM/L vs 428nM/L, p<0.001). SMRP predicted MPM with an AUC of 0.93 (0.86-0.99) giving 95% sensitivity and 86% specificity at a threshold of 1150nM/L. In the analysis of prognostic factors patient age, smoking status, chest pain, weight loss, PLT count, Urea and Adjusted Calcium were independently associated with survival. Being a current smoker carried the highest hazard ratio 3.42 (1.11, 4.2) p=0.03. The RESPECT-Meso study was unable to demonstrate a difference in QOL with early SPC compared to standard care with a 1.8 mean difference between groups (95%CI: -4.9 to 8.5; p=0.59). Conclusions: This body of work evaluating three components of MPM care concludes, SMRP as a biomarker with a significant ability to predict MPM from other causes of pleural effusion in a real world clinical setting. Seven prognostic factors identified may aid clinicians to better prognosticate when planning treatments in MPM. Finally the results of the RESPECT-Meso study are reassuring of the exiting care pathway for MPM.
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