Clinical significance of non-expansile lung and development of a stratified treatment pathway in malignant pleural effusion

Martin, Geoffrey A. (2021) Clinical significance of non-expansile lung and development of a stratified treatment pathway in malignant pleural effusion. MD thesis, University of Glasgow.

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Malignant pleural effusion (MPE) is a common and regularly debilitating complication in a wide range of cancers. MPE confers a short prognosis (3-12 months depending on the primary tumour) and efficient, enduring palliation is therefore a clinical priority. Non-expansile lung (NEL) frequently complicates definitive MPE management as it precludes successful talc slurry pleurodesis (TSP) resulting in recurrent symptoms and repeat pleural interventions.
Indwelling pleural catheters (IPCs) may provide reliable symptom relief in the presence of NEL, but are not universally acceptable to patients. The aim of this thesis was to progress towards improving outcomes in MPE through the reliable detection of NEL. In Chapter 3, an observational multicentre cohort of patients with MPE diagnosed at local anaesthetic thoracoscopy identified NEL in 17-34%.
Radiographic identification of NEL was subject to a high level of inter-observer variation (k 0.38–0.51). NEL was also associated with adverse survival (HR 2.2, 95% CI 1.3–3.7), although the independence of this relationship was not externally validated. Chapter 4 presents the results of a feasibility randomised controlled trial (RCT) of a pleural elastance (PEL)-directed treatment pathway (Elastance-Directed IPC or TSP (EDIT management)) for symptomatic MPE. This trial, abbreviated to ‘pre-EDIT’, demonstrated the feasibility of this RCT design and treatment pathway in terms of recruitment rate (2.4 subjects/month), technical delivery (successful PEL assessment in 13/15 (87%) and 13/13 (100%) after an early equipment update) and safety (no directly attributable serious adverse events). Finally, in Chapter 5, additional data from pre-EDIT and an
embedded treatment preferences survey (TPS) were explored to optimise the proposed EDIT pathway. Only 4/17 TPS respondents (24%) would choose first-line ambulatory pleurodesis via an IPC if offered, whereas 15/17 (88%) stated they would consider a 2-stage pleural intervention process incorporating PEL assessment. Motion-mode sonographic assessment performed poorly as an alternative pre-drainage NEL biomarker; adequate imaging was achieved in only 10/13 (77%) and the AUC for NEL detection was 0.595 (95%CI 0.180-1.000). Novel volumetric magnetic resonance imaging pre- and post-aspiration from pre-EDIT validated the widely adopted clinical definition of PEL and further supports the use of PEL as a NEL biomarker. The findings from these chapters are incorporated into a proposed design for a Phase III trial of the efficacy of EDIT management.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Malignant pleural effusion, trapped lung, non-expansile lung, unexpandable lung, pleural manometry, pleural elastance.
Subjects: R Medicine > R Medicine (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Supervisor's Name: Chalmers, Professor Anthony and Blyth, Professor Kevin G.
Date of Award: 2021
Depositing User: Dr Geoffrey A Martin
Unique ID: glathesis:2021-82190
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 18 May 2021 07:58
Last Modified: 27 Jul 2021 10:14
Thesis DOI: 10.5525/gla.thesis.82190
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