Reflecting real-world patients with mesothelioma in research: an interim report of baseline characteristics from the ASSESS-meso cohort.

Objective: Mesothelioma varies in clinical phenotype and survival. Clinical trials are unavoidably affected by selection bias, reducing generalisability. ASSESS-meso is a UK, multicentre, prospective, mesothelioma cohort study (ISRCTN61861764). This pre-specified interim analysis, conducted when recruitment reached 25% of target, summarised participant characteristics and evaluated external validity through comparison with real-world and clinical trial cohorts. Methods: The study took place at 14 hospitals across the UK. People diagnosed with mesothelioma, at any anatomical site, were eligible. Clinical, radiological and biochemical data were collected at enrolment. In this interim report, the external validity of the cohort was investigated through comparison of baseline demographic data with populations included in the 2020 UK National Mesothelioma Audit (real-world cohort), and CHECKMATE-743 and MAPS trials (clinical trial cohorts). Results: 244 patients were enrolled between 7 April 2017 and 1 March 2022. The cohort was predominantly male (195 out of 244; 80%) with a median age of 74 years. Pleural disease and epithelioid subtypes were most prevalent. ASSESS-meso participants were more similar to the real-world population with regard to age, performance status, disease site and stage than the clinical trial population. ASSESS-meso participants were more likely to be formally staged and less likely to have undifferentiated histology compared with the real-world cohort, possibly reflecting high rates of discussion of ASSESS-meso participants at regional mesothelioma multidisciplinary team meetings. As expected, poorer performance status, non-epithelioid histology and neutrophil-lymphocyte ratio were associated with shorter survival in the adjusted analysis. Conclusion: ASSESS-meso is representative of the UK mesothelioma population. Future outputs from the cohort will help characterise different mesothelioma phenotypes with high external validity.

A feasibility randomised trial comparing therapeutic thoracentesis to chest tube insertion for the management of pleural infection: results from the ACTion trial.

BACKGROUND: Pleural infection is a complex condition with a considerable healthcare burden. The average hospital stay for pleural infection is 14 days. Current standard of care defaults to chest tube insertion and intravenous antibiotics. There have been no randomised trials on the use of therapeutic thoracentesis (TT) for pleural fluid drainage in pleural infection. AIMS AND OBJECTIVES: To assess the feasibility of a full-scale trial of chest tube vs TT for pleural infection in a single UK centre. The primary outcome was defined as the acceptability of randomisation to patients. METHODS: Adult patients admitted with a pleural effusion felt to be related to infection and meeting criteria for drainage (based on international guidelines) were eligible for randomisation. Participants were randomised (1:1) to chest tube insertion or TT with daily review assessing need for further drainages or other therapies. Neither participant nor clinician were blinded to treatment allocation. Patients were followed up at 90 days post-randomisation. RESULTS: From September 2019 to June 2021, 51 patients were diagnosed with pleural infection (complex parapneumonic effusion/empyema). Eleven patients met the inclusion criteria for trial and 10 patients were randomised (91%). The COVID-19 pandemic had a substantial impact on recruitment. Data completeness was high in both groups with no protocol deviations. Patients randomised to TT had a significantly shorter overall mean hospital stay (5.4 days, SD 5.1) compared to the chest tube control group (13 days, SD 6.0), p = 0.04. Total number of pleural procedures required per patient were similar, 1.2 in chest tube group and 1.4 in TT group. No patient required a surgical referral. Adverse events were similar between the groups with no readmissions related to pleural infection. CONCLUSIONS: The ACTion trial met its pre-specified feasibility criteria for patient acceptability but other issues around feasibility of a full-scale trial remain. From the results available the hypothesis that TT can reduce length of stay in pleural infection should be explored further. TRIAL REGISTRATION: ISRCTN: 84674413.

Is Systemic Anticancer Therapy Associated With Higher Rates of Malignant Pleural Effusion Control in People With Pharmacologically Sensitive Tumors?: A Retrospective Analysis of Prospectively Collected Data.

BACKGROUND: Malignant pleural effusions (MPEs) often cause symptoms, and guidelines recommend early definitive intervention. However, observational data suggest that systemic anticancer treatment (SACT) may control MPE caused by certain pharmacologically sensitive tumors. RESEARCH QUESTION: Is SACT associated with higher rates of MPE resolution in people with pharmacologically sensitive tumors? STUDY DESIGN AND METHODS: This was a retrospective analysis of prospectively collected data from an observational cohort study of people diagnosed with MPE from lung, breast, ovarian, and hematologic malignancy between May 11, 2008, and August 6, 2017. MPE resolution (defined as radiologic resolution with removal of drain or catheter and cessation of interventions) was compared in pharmacologically sensitive (high-grade lymphoma, small cell or target-mutation-positive lung cancer, and hormone-receptor-positive breast or ovarian cancer) and nonsensitive (remainder of cohort) tumors, with and without SACT. Secondary outcomes included time to resolution, 3-month resolution rates, and total pleural interventions. RESULTS: Of 280 patients, 127 had sensitive and 153 had nonsensitive tumors. One hundred seventy-one received SACT, and 109 did not. More patients with sensitive tumors achieved MPE resolution than those with nonsensitive tumors (53/127 [41.7%] vs 42/153 [27.5%]; P = .01), and this occurred predominantly after receipt of SACT. However, hematologic malignancies were overrepresented in the sensitive group, with high rates of SACT use and MPE resolution. After adjustment for this and other confounders, no relationship was found among pharmacologic sensitivity, SACT, and MPE resolution (adjusted OR, 1.4; 95% CI, 0.5-4.1). The strongest predictor of MPE resolution was administration of chemical pleurodesis (adjusted OR, 6.2; 95% CI, 3.3-11.7). In sensitive tumors, MPE resolution occurred without chemical pleurodesis in 14 of 52 patients (26.9%; 95% CI, 15.6%-41.1%) after SACT and in 5 of 22 patients (22.7%; 95% CI, 8.2%-47.2%) without SACT. INTERPRETATION: In this observational study, SACT was not associated independently on MPE resolution in pharmacologically sensitive tumors. Randomized trials are required, but with current data, patients with symptomatic MPE should receive early definitive pleural intervention regardless of underlying tumor or intended treatment.

Investigation of a unilateral pleural effusion: What CT scan coverage is optimal?

The use of thoracic CT for patients presenting with a unilateral pleural effusion is well established. However, there is no consensus with regard to the inclusion of the entire abdomen and pelvis in the initial imaging protocol. In this prospective UK-based study, 249 patients presenting with a unilateral effusion had a CT thorax/abdomen/pelvis performed. The prevalence of malignancy on thoracic CT was 56% (140/249). Clinically significant findings below the diaphragm were identified in 59 patients (24%). Integrating this approach into standard practice allows more rapid identification of the primary malignancy, upstaging lesions or alternative sites for biopsy.

Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions.

Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P < 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.