Title: Smarter Therapeutic and Diagnostic Intervention in Malignant Pleural Effusion (STREAMLINE) - a Feasibility Randomised Study with Qualitative Components
Funder: Department of Health and Social Care

Abstract: BackgroundMalignant pleural effusion (MPE) is extremely common with an annual UK incidence of 50,000/year. It is typically associated with rapidly progressive symptoms and a 3-12 month life expectancy. Under the current (decade old) UK and European management guidelines, patients typically undergo multiple procedures to achieve a diagnosis that can guide treatment ('actionable histology'). International guidelines mandate pleural aspiration as a first diagnostic and therapeutic step (procedure 1), followed by biopsy (procedure 2) and finally definitive effusion control with talc pleurodesis or Indwelling pleural catheter (IPC, procedure 3). Between procedures, patients often require further procedures or admission for breathlessness due to recurrent effusion, and recent data illustrates pleural aspiration alone is rarely sufficient to guide treatment. Hypothesis:I hypothesise that a novel, accelerated pathway, based on my pilot work with MPE patients and data on diagnostic yield will improve overall breathlessness and time to diagnosis. The accelerated pathway will conduct the index procedure as a personalised biopsy (according to likely primary), AND simultaneous insertion of indwelling pleural catheter. As this represents a more invasive first procedure and potential 'over-treatment' in some, with a long term pleural catheter, a pilot study is required to ascertain feasibility before a definitive study. MethodsI will conduct 3 work streams (WS): WS1: Systematic review (SR) appraising optimal therapeutic intervention in MPE, addressing patient reported outcomes and quality of life which have been under-utilised previously. I will conduct an SR of the existing evidence for therapeutic interventions in MPE, covering talc pleurodesis, IPC insertion and repeated aspiration. The novel focus of this SR will be patient reported symptoms and quality of life as the primary outcomes, rather than (previously studied) pleurodesis success, as improving quality of life is the main goal. WS2: STREAMLINE (Smarter Therapeutic and Diagnostic Intervention in Malignant Pleural Effusion) : Feasibility StudyWe will conduct a randomised controlled trial of an accelerated, personalised pathway combining pleural biopsy and IPC insertion as the first intervention in suspected MPE versus standard pathway, in 40 patients randomised 1:1 across 2 centres. We will proceed with a definitive clinical trial (separate future funding) based on pre-determined stop/go feasibility criteria. We will assess the impact of the accelerated pathway on patient symptoms including breathlessness (validated 100mm Visual-Analogue-Scale), quality of life (EORTC QLQ-C30 questionnaire), mood (Hospital Anxiety Depression Scale) and time to treatable diagnosis as the outcome measures for a definitive trial. WS3: Qualitative study to establish the day to day impact of the standard vs streamline pathway on patients lives, experiences and those of their carers and familyI will undertake qualitative interviews with 20 patients from WS2 to ascertain the impact of the old and novel pathway on patients and acceptability of the accelerated pathway. Impact and DisseminationCompletion will underpin a definitive trial of the STREAMLINE pathway versus the current pathway which could re-define MPE management and international guidelines, changing practice for thousands of patients yearly. Work will be published in high impact peer reviewed journals, patient facing newsletters and circulated via social media.

Lay abstract: BackgroundA malignant pleural effusion (MPE) is a buildup of fluid around the lungs due to any type of cancer that has either started in or spread to the lining of the lungs (pleura). This affects over 100 people per day in the UK. Typically people with MPE experience breathlessness due to fluid and wait long periods with multiple procedures required to reach a diagnosis, often delaying treatment with chemotherapy. In the current pathway, patients with suspected MPE first have some fluid drawn off to relieve symptoms and the fluid is analysed. The fluid often does not provide a diagnosis and and the patient returns for biopsies of the lung lining. Once a diagnosis is secured, steps to stop the fluid returning are taken, one of which is to insert a long term tube in the chest (indwelling pleural catheter, IPC) which can be used 2-3 times/week to let fluid out (done by a nurse or patient). In the current pathway, patients wait 6-8 weeks for diagnosis and long term control of fluid and breathlessness. This is a hugely significant time as life expectancy in MPE is 3-12 months. AimsWe aim to assess if a new accelerated pathway involving fewer procedures to reach a diagnosis and long term control of fluid is acceptable to patients and can be faster, and reduce breathlessness in MPE. Design and MethodsThe project consists of three related work streams (WS) WS1: Summarising what we know about the current patient experience of MPE There have been a number of studies looking at cancer related fluid buildup around the lung, but very few focusing on patient symptoms, experience and time to diagnosis while they are having tests to find a cause for the fluid. Bringing together these studies in an analysis and paper will help further focus our trial. WS2: Feasibility and acceptability of the streamlined pathway We aim to enroll 40 patients who have scans suggestive of cancer related fluid buildup around the lungs and they will either be treated in the current/'standard' pathway or the new accelerated pathway. The accelerated pathway means that patients will have a biopsy as part of the first visit, which gives the highest likelihood of reaching a diagnosis, and in the same visit, the patients will have a long term chest tube fitted so they are not left breathless and needing multiple procedures. We need to know whether the new pathway is acceptable to patients (as the first procedure is more extensive, and may in a small proportion of patients result in 'over-treatment'), and how many patients we can recruit and how many patients complete the study. We will assess overall breathlessness, time to diagnosis and quality of life within the old and new pathway. WS3: Assessing the true patient experience of both pathwaysWe will conduct patient interviews (qualitative research) talking to patients about their true experience of both pathways and their views on strengths and weaknesses of each pathway. This ensures that any new pathway is focussed on what matters to patients.Patient/Public InvolvementTo prepare this application, I convened a focus-group of 12 patients with MPE who had heavy input on the trial design. They provided opinions on their priorities of care (reducing breathlessness and time to diagnosis), willingness to have a pleural biopsy and long term pleural catheter at their first procedure, and on the questionnaires that will be used. DisseminationWe will present our results at patient support groups and in the British Lung Foundation newsletter. The research will be presented at national conferences, scientific journals and on the mypleuraleffusionjourney.com patient website.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS