The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.

Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Fully automated volumetric measurement of malignant pleural mesothelioma by deep learning AI: validation and comparison with modified RECIST response criteria.

BACKGROUND: In malignant pleural mesothelioma (MPM), complex tumour morphology results in inconsistent radiological response assessment. Promising volumetric methods require automation to be practical. We developed a fully automated Convolutional Neural Network (CNN) for this purpose, performed blinded validation and compared CNN and human response classification and survival prediction in patients treated with chemotherapy. METHODS: In a multicentre retrospective cohort study; 183 CT datasets were split into training and internal validation (123 datasets (80 fully annotated); 108 patients; 1 centre) and external validation (60 datasets (all fully annotated); 30 patients; 3 centres). Detailed manual annotations were used to train the CNN, which used two-dimensional U-Net architecture. CNN performance was evaluated using correlation, Bland-Altman and Dice agreement. Volumetric response/progression were defined as ≤30%/≥20% change and compared with modified Response Evaluation Criteria In Solid Tumours (mRECIST) by Cohen's kappa. Survival was assessed using Kaplan-Meier methodology. RESULTS: Human and artificial intelligence (AI) volumes were strongly correlated (validation set r=0.851, p<0.0001). Agreement was strong (validation set mean bias +31 cm3 (p=0.182), 95% limits 345 to +407 cm3). Infrequent AI segmentation errors (4/60 validation cases) were associated with fissural tumour, contralateral pleural thickening and adjacent atelectasis. Human and AI volumetric responses agreed in 20/30 (67%) validation cases κ=0.439 (0.178 to 0.700). AI and mRECIST agreed in 16/30 (55%) validation cases κ=0.284 (0.026 to 0.543). Higher baseline tumour volume was associated with shorter survival. CONCLUSION: We have developed and validated the first fully automated CNN for volumetric MPM segmentation. CNN performance may be further improved by enriching future training sets with morphologically challenging features. Volumetric response thresholds require further calibration in future studies.

A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.

BACKGROUND: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. METHODS: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. RESULTS: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). CONCLUSION: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial.

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.

Ambulatory management of primary spontaneous pneumothorax: an open-label, randomised controlled trial.

BACKGROUND: Primary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. We aimed to describe the duration of hospitalisation and safety of ambulatory management compared with standard care. METHODS: In this open-label, randomised controlled trial, adults (aged 16-55 years) with symptomatic primary spontaneous pneumothorax were recruited from 24 UK hospitals during a period of 3 years. Patients were randomly assigned (1:1) to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion, or both). The primary outcome was total length of hospital stay including re-admission up to 30 days after randomisation. Patients with available data were included in the primary analysis and all assigned patients were included in the safety analysis. The trial was prospectively registered with the International Standard Randomised Clinical Trials Number, ISRCTN79151659. FINDINGS: Of 776 patients screened between July, 2015, and March, 2019, 236 (30%) were randomly assigned to ambulatory care (n=117) and standard care (n=119). At day 30, the median hospitalisation was significantly shorter in the 114 patients with available data who received ambulatory treatment (0 days [IQR 0-3]) than in the 113 with available data who received standard care (4 days [IQR 0-8]; p<0·0001; median difference 2 days [95% CI 1-3]). 110 (47%) of 236 patients had adverse events, including 64 (55%) of 117 patients in the ambulatory care arm and 46 (39%) of 119 in the standard care arm. All 14 serious adverse events occurred in patients who received ambulatory care, eight (57%) of which were related to the intervention, including an enlarging pneumothorax, asymptomatic pulmonary oedema, and the device malfunctioning, leaking, or dislodging. INTERPRETATION: Ambulatory management of primary spontaneous pneumothorax significantly reduced the duration of hospitalisation including re-admissions in the first 30 days, but at the expense of increased adverse events. This data suggests that primary spontaneous pneumothorax can be managed for outpatients, using ambulatory devices in those who require intervention. FUNDING: UK National Institute for Health Research.

Intrapleural Fibrinolytics and Deoxyribonuclease for Treatment of Indwelling Pleural Catheter-Related Pleural Infection: A Multi-Center Observational Study.

BACKGROUND: Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce. OBJECTIVE: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. METHODS: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded. RESULTS: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3-6]/patient) of tPA (2.5 mg-10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding. CONCLUSION: Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common.

Inter-observer variation in image interpretation and the prognostic importance of non-expansile lung in malignant pleural effusion.

BACKGROUND AND OBJECTIVE: Non-expansile lung (NEL) frequently complicates management of malignant pleural effusion (MPE) and is an important factor in clinical practice and trials. NEL is frequently diagnosed on a single radiographic observation, but neither the inter-observer agreement of this approach nor the prognostic importance of NEL in MPE has been reported. METHODS: A multicentre retrospective cohort study was performed in two UK pleural centres. NEL was defined as <50% pleural re-apposition on post-drainage radiographs by primary and secondary assessors at each site. Inter-observer agreement was assessed by Cohen's kappa (κ). Kaplan-Meier methodology and multivariate Cox models were used to assess the prognostic impact of NEL versus no NEL and 'complete NEL' versus 'complete expansion', based on a single assessor's results from each site. RESULTS: NEL was identified by the primary assessor in 33 of 97 (34%) in Cohort 1 and 15 of 86 (17%) in Cohort 2. Inter-observer agreement between assessors was only fair-to-moderate (Cohort 1 κ: 0.38 (95% CI: 0.21-0.55), Cohort 2 κ: 0.51 (95% CI: 0.30-0.72)). In both cohorts, NEL was associated with shorter median overall survival (Cohort 1: 188 vs 371 days, Cohort 2: 192 vs 412 days). This prognostic association was independent in Cohort 1 (hazard ratio (HR): 2.19, 95% CI: 1.31-3.66) but not in Cohort 2 (HR: 1.42, 95% CI: 0.71-2.87). Survival was inferior in both cohorts in cases of complete NEL versus complete expansion. CONCLUSION: Radiographic NEL is common but inter-observer agreement is only fair-to-moderate. NEL is associated with adverse survival. These data do not support the use of single radiographic assessments to classify NEL.

Advanced Symptom Management System for Patients with Malignant Pleural Mesothelioma (ASyMSmeso): Mixed Methods Study.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) have a life-limiting illness and short prognosis and experience many debilitating symptoms from early in the illness. Innovations such as remote symptom monitoring are needed to enable patients to maintain wellbeing and manage symptoms in a proactive and timely manner. The Advanced Symptom Management System (ASyMS) has been successfully used to monitor symptoms associated with cancer. OBJECTIVE: This study aimed to determine the feasibility and acceptability of using an ASyMS adapted for use by patients with MPM, called ASyMSmeso, enabling the remote monitoring of symptoms using a smartphone. METHODS: This was a convergent mixed methods study using patient-reported outcome measures (PROMs) at key time points over a period of 2-3 months with 18 patients. The Sheffield Profile for Assessment and Referral for Care (SPARC), Technology Acceptance Model (TAM) measure for eHealth, and Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso) were the PROMs used in the study. Patients were also asked to complete a daily symptom questionnaire on a smartphone throughout the study. At the end of the study, semistructured interviews with 11 health professionals, 8 patients, and 3 carers were conducted to collect their experience with using ASyMSmeso. RESULTS: Eighteen patients with MPM agreed to participate in the study (33.3% response rate). The completion rates of study PROMs were high (97.2%-100%), and completion rates of the daily symptom questionnaire were also high, at 88.5%. There were no significant changes in quality of life, as measured by LCSS-Meso. There were statistically significant improvements in the SPARC psychological need domain (P=.049) and in the "Usefulness" domain of the TAM (P=.022). End-of-study interviews identified that both patients and clinicians found the system quick and easy to use. For patients, in particular, the system provided reassurance about symptom experience and the feeling of being listened to. The clinicians largely viewed the system as feasible and acceptable, and areas that were mentioned included the early management of symptoms and connectivity between patients and clinicians, leading to enhanced communication. CONCLUSIONS: This study demonstrates that remote monitoring and management of symptoms of people with MPM using a mobile phone are feasible and acceptable. The evidence supports future trials using remote symptom monitoring to support patients with MPM at home.

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

Lung cancer symptom appraisal among people with chronic obstructive pulmonary disease: A qualitative interview study.

OBJECTIVE: The incidence of lung cancer is four times higher in people with chronic obstructive pulmonary disease (COPD) compared with the general population. Promotion of a shorter time from symptom onset to presentation is one potential strategy for earlier lung cancer diagnosis, but distinguishing respiratory symptoms can be difficult. We investigated how the experience of COPD influences symptom appraisal and help seeking for potential lung cancer symptoms. METHODS: We conducted qualitative interviews with men (n = 17) and women (n = 23) aged 40 to 83 years with COPD. Topic guides drew on the integrated symptom-response framework and covered symptom experience, interpretation, action, recognition, help seeking, evaluation, and reevaluation. We used the framework method to analyse the data. RESULTS: Participants said that they attributed chest symptoms to their COPD; no other cause was considered. Participants said that family/friends noticed changes in their symptoms and encouraged help seeking. Others felt isolated by their COPD because they could not get out, were fatigued, or were embarrassed. Participants visited health professionals frequently, but increased risk of lung cancer was not discussed. CONCLUSIONS: Our study provides insight into different levels of influence on symptom appraisal and targets for intervention. Greater awareness of increased lung cancer risk and support to act on symptom changes is essential and could be achieved through a concerted information campaign. Health professionals working with people with COPD could also optimise appointments to support symptom appraisal of potential lung cancer symptoms.

Contemporary management of mesothelioma.

Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets.

New developments in the imaging of lung cancer.

Radiological and nuclear medicine methods play a fundamental role in the diagnosis and staging of patients with lung cancer. Imaging is essential in the detection, characterisation, staging and follow-up of lung cancer. Due to the increasing evidence, low-dose chest computed tomography (CT) screening for the early detection of lung cancer is being introduced to the clinical routine in several countries. Radiomics and radiogenomics are emerging fields reliant on artificial intelligence to improve diagnosis and personalised risk stratification. Ultrasound- and CT-guided interventions are minimally invasive methods for the diagnosis and treatment of pulmonary malignancies. In this review, we put more emphasis on the new developments in the imaging of lung cancer.

Imaging of pleural disease.

The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or by abnormal accumulation of air or liquid. Chest radiographs are often the first imaging tests to point to a pleural pathology. With the exception of pneumothorax, and due to the inherent limitations of chest radiographs, ultrasound and/or computed tomography are usually required to further characterise the pleural pathology and guide management. This review summarises the utility of different imaging tools in the management of pleural disease and discusses new and evolving tools in imaging of the pleura.

Imaging in pleural Mesothelioma: A review of the 16th International Conference of the International Mesothelioma Interest Group.

Imaging continues to gain a greater role in the assessment and clinical management of patients with mesothelioma. This communication summarizes the oral presentations from the imaging session at the 2023 International Conference of the International Mesothelioma Interest Group (iMig), which was held in Lille, France from June 26 to 28, 2023. Topics at this session included an overview of best practices for clinical imaging of mesothelioma as reported by an iMig consensus panel, emerging imaging techniques for surgical planning, radiologic assessment of malignant pleural effusion, a radiomics-based transfer learning model to predict patient response to treatment, automated assessment of early contrast enhancement, and tumor thickness for response assessment in peritoneal mesothelioma.

Leveraging the pleural space for anticancer therapies in pleural mesothelioma.

Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.