Title: Reaccumulation rate of Malignant Pleural Effusions After Therapeutic Aspiration (REPEAT): an observational cohort study to create a multivariable prediction model of rate of pleural fluid reaccumulation following therapeutic aspiration in patients with malignant pleural effusion attending a pleural clinic
Funder: Department of Health and Social Care

Abstract: Research question Can we predict how quickly pleural fluid will reaccumulate in patients with malignant pleural effusions (MPEs)? Background MPE is the build up of pleural fluid in the space between the lung and chest wall due to advanced cancer. It is treated initially by large volume drainage (therapeutic aspiration). If the fluid reaccumulates, a definitive procedure is performed. There is wide variation in rate of reaccumulation. Patients with rapid reaccumulation often attend hospital as an emergency. Conversely, patients with slow reaccumulation do not need a definitive procedure and may experience cancelled or unnecessary procedures. Aims and Objectives Aim: To create, validate and assess a multivariable prediction model to predict how quickly pleural fluid will reaccumulate in individual patients with MPE following therapeutic aspiration. This study is divided into three phases: Phase 1: use a development cohort of 200 patients to create a clinical score to predict rate of pleural fluid reaccumulation. Phase 2: validate the model in a separate cohort of 40 patients. Phase 3 (to be funded separately if the first two phases are successful): assess the health and economic impact of using the score to guide clinical practice, specifically assessing number of procedures, emergency admissions and health-related quality of life. Methods Phase 1: Two hundred patients with known or suspected MPE attending for therapeutic aspiration will be recruited from 5 UK hospitals over 20 months. Patients will be enrolled prior to undergoing aspiration. Following this, they will undergo chest X-ray, the X-ray will be repeated 1 week later (treatment as usual). Rate of reaccumulation will be calculated based on change of size of the effusion seen on X-ray. Data will be collected on common clinical biomarkers e.g. size of effusion on pre-aspiration chest X-ray, volume of fluid drained. This data will be analysed to create a clinical score. Phase 2: A further validation cohort will be enrolled in parallel with creation of the score. This will be used to validate the score's ability to predict rate of reaccumulation. Timelines for delivery Finalise protocol and submit ethics application: July-October 2020 Study set up: November 2020-February 2021 Phase 1 recruitment: March 2021 - October 2022, 3 months follow up until January 2023 Phase 2 recruitment: November 2022&ndash; April 2023, 3 months follow up until June 2023 Analysis and derivation and validation of score, publication and dissemination of results: May 2023 &ndash; October 2023 Anticipated Impact and Dissemination The ability to predict rate of reaccumulation of MPE will enable patients and clinicians to make better informed treatment decisions. For patients with predicted rapid reaccumulation, a definitive procedure could be offered as first-line treatment, rather than a therapeutic aspiration. This will prevent emergency hospital admissions and decrease number of procedures. In contrast, patients whose effusions will recur slowly may avoid an unnecessary procedure. We will disseminate these results through national and international meetings, publication in a peer-reviewed journal and local and national patient groups.

Lay abstract: People with incurable cancer commonly feel breathless due to build up of fluid around the lung. Aims of treatment are to help symptoms and prevent admission to hospital. We do this by draining fluid off, but it often comes back. When this happens, we offer the patient a permanent implanted drain, so they can drain the fluid off regularly at home. However, sometimes the fluid builds up very quickly, before we have time to implant a drain. The patient becomes very breathless and needs an emergency hospital admission. In other people, the fluid builds up slowly and they may never need another drain. The aim of this study is to improve treatment by finding a way to predict how quickly fluid will come back. It will be run in 5 hospitals across England and involve 240 patients over 3 years. When patients first come to have fluid drained, we will record information about them and their disease. We will measure how quickly the fluid comes back by comparing their chest X-ray after draining the fluid with their chest X-ray a week later. We will record hospital admissions and need for fluid drainage over the following 3 months. We will use this information to create a clinical score which can predict how quickly fluid will come back. We will then test this score in a second group of patients to make sure it works. The study is designed so that people don t have to make extra hospital visits or have extra tests, which means there are no disadvantages for people who get involved. We have already tested this trial design in 20 patients to show we can do it. The idea for this study came from one of our patients who had just had fluid drained and asked, when will it come back? We couldn t answer his question and therefore developed this study to answer it for other patients in the future. Our patients, including those involved in testing the trial design, and members of the public have been involved in the design of this study and will continue to be involved to ensure that it will improve their treatment. This score will be used to inform patients so they can choose the best treatment for them. If we know the fluid will build up quickly, we can offer patients a permanent drain straight away. This will control their breathlessness better and prevent them coming into hospital. On the other hand, if patients know their fluid will build up slowly, they may choose simply to have the fluid drained when needed without a permanent drain.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS