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

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– April 2023, 3 months follow up until June 2023 Analysis and derivation and validation of score, publication and dissemination of results: May 2023 – 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.