Interventions to improve health-related quality of life in malignant pleural effusion

Student thesis: Doctoral ThesisDoctor of Medicine by Research


Malignant pleural effusions (MPE) are collections of fluid in the pleural space related to advanced cancer. They result in debilitating breathlessness with reduced physical function and impaired quality of life. Multiple interventional therapeutic options are available, all of which are centred on a palliative strategy that primarily aims to improve quality of life. However, limited research exists on quality of life outcomes in this patient population.

The aims of this thesis are as follows:
1. To review the current evidence of the impact of interventions for MPE on health-related quality of life (HRQOL).
2. To investigate clinicians’ perspectives on interventions to improve HRQOL
in MPE.
3. To determine if an outpatient ambulatory pathway that utilises an indwelling pleural catheter (IPC) with the option of talc pleurodesis improves HRQOL over standard inpatient treatment with a chest tube and
talc pleurodesis.

The first aim was addressed utilising a systematic search and review that was most recently updated in 2021. Of 1,072 screened studies, the review included 19 studies that reported HRQOL outcomes. Thoracoscopic talc pleurodesis, talc slurry pleurodesis via a chest drain and IPCs were associated with modest but inconsistent improvements in HRQOL in the 12 weeks following intervention. No intervention was significantly different from another in HRQOL outcomes at any time point. Due to high attrition rates, there was insufficient data for comparison beyond 12 weeks. Total adverse events were lower in the IPC group than in thoracoscopic talc pleurodesis or talc slurry pleurodesis. The heterogeneity of the data prevented a meta-analysis and the small number of comparative studies limit the evidence for the most effective treatment strategy.

The second aim was achieved utilising an international Internet-based survey of respiratory physicians. 150 doctors (121 from the UK, 19 from Australia and 10 from New Zealand) responded with their perspectives on HRQOL and factors that affect their practices regarding MPE. The key treatment priority for these physicians was improvement in HRQOL; however, there was a lack of consensus on the ideal treatment to maximise HRQOL. Of participating clinicians, 43% believed an IPC with or without talc pleurodesis most improves HRQOL, whereas 10% were in favour of a chest drain and talc pleurodesis. Symptoms of shortness of breath and chest pain were perceived to have the greatest impact on HRQOL outcomes, with shortness of breath being the dominant factor in offering an intervention.

The findings from the first two aims informed the research question implied in Aim 3. This was addressed by designing and conducting an international, multicentre, randomised trial that recruited patients with symptomatic MPE from 12 U.K. and Australian hospitals; 142 participants were enrolled and monitored for three months. Patients were randomised 1:1 to an IPC (with the option of outpatient talc pleurodesis) or chest drain with talc slurry pleurodesis; they were stratified by malignancy, age, and performance status. The primary endpoint was global health status, which was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, a cancer-specific HRQOL questionnaire, at 30 days post-intervention. The minimal important between-group difference for global health status is 8 points. Of participants randomly assigned to IPC (n = 70) and chest drain (n = 72), primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups, with no significant between-group difference in global health status scores at Day 30 (1.12 points [95% CI -6.80 to 9.04]; p = 0.78), Day 60 (mean inter-group difference of 4.82 points [95% CI -4.59 to 14.23]; p = 0.31) and Day 90 (mean inter-group difference of -3.12 points [95% CI -13.76 to 7.51]; p = 0.56). Additionally, no significant between-group differences were observed in breathlessness and chest pain scores. Twenty-nine of the 65 participants in the IPC group and 49 of 67 in the chest tube group received talc pleurodesis; non-expandable lung (31) and ongoing high fluid output (15) were the main reasons for withholding talc. The cumulative rate of pleurodesis failure in the IPC group (defined as IPC remaining in situ, need for subsequent pleural intervention or chest x-ray opacification of >25% hemithorax) was 64.2% at Day 30; 67.9% at Day 60; and 71.4% at Day 90. Pleurodesis failure in the chest drain group (defined as a need for subsequent pleural intervention or chest x-ray opacification of >25% hemithorax) was 18.4% at Day 30; 24.5% at Day 60; 26.5% at Day 90. All chest drain group patients were admitted; only seven in the IPC arm required intervention-related hospitalisation.

This work reveals a that employing an outpatient pathway that utilises an IPC is not superior to inpatient treatment with a chest drain in improving patient-reported global health status at 30 days. This finding challenges current perspectives in MPE management. If, for the patient, an improvement of HRQOL is the primary goal, then treatment choices should be tailored to clinical parameters, patient preferences and values, treatment accessibility and affordability. More work is needed to evaluate patients’ perspectives on their HRQOL, to develop a disease- specific questionnaire for usage in future research studies and to support shared decision-making in this condition.
Date of Award1 Mar 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorNicholas Hart (Supervisor) & Ronan Breen (Supervisor)

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