Anna C. Bibby

Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.

Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years. This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised. This article on mesothelioma describes pathogenesis, symptoms, diagnostic approaches and treatment options http://ow.ly/cjkb305aQGz

Pleural biopsies in undiagnosed pleural effusions; Abrams vs image-guided vs thoracoscopic biopsies.

Purpose of review Pleural biopsies are often necessary if a pleural effusion remains undiagnosed after radiological imaging and pleural fluid analysis. There are many methods of obtaining pleural biopsies, including blind or image-guided procedures, closed-bevel or cutting-edge needles, and percutaneous or thoracoscopic approaches. This article will review recent research relating to these methods, aiming to provide an overview of the strengths and limitations of each technique. Recent findings Historically pleural biopsies were undertaken using a blind closed ‘Abrams’ needle method. However, low diagnostic yields and high complication rates are seen with this technique compared with newer methods. Recent research compares image-guided, cutting-needle approaches to traditional Abrams biopsies, and evaluates the role of medical thoracoscopy in comparison to other techniques. Summary Thoracoscopic biopsies are the gold standard for investigating pleural disease. However, this service is not universally available and may be unsuitable for some patients. Image-guided cutting-needle biopsies under computed tomography or ultrasound guidance have high diagnostic rates and are useful in a wide patient population. The main role of Abrams biopsies is in the diagnosis of tuberculous pleuritis in resource-poor settings.

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion

BACKGROUND Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single‐blind basis. Follow‐up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between‐group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012–000599–40.)

What is the role of a specialist regional mesothelioma multidisciplinary team meeting? A service evaluation of one tertiary referral centre in the UK

Background Multidisciplinary team meetings are standard care for cancer in the UK and Europe. Professional bodies recommend that mesothelioma cases should be discussed at specialist multidisciplinary team meetings. However, no evidence exists exploring the role of the specialist mesothelioma multidisciplinary team meeting. Objectives To evaluate the clinical activity of 1 specialist mesothelioma multidisciplinary team meeting and to determine how often a definitive diagnosis was made, whether the core requirements of the meeting were met and whether there was any associated benefit or detriment. Design and setting A service evaluation using routinely collected data from 1 specialist mesothelioma multidisciplinary team meeting in a tertiary referral hospital in the South-West of England. Participants All cases discussed between 1/1/2014 and 31/12/2015. Outcome measures The primary outcome measure was whether a definitive diagnosis was made. Secondary outcomes included whether treatment advice was offered, information on clinical trials provided or further investigations suggested. Additional benefits of the multidisciplinary team meeting and time taken from referral to outcome were also collected. Results A definitive diagnosis was reached in 171 of 210 cases discussed (81%). Mesothelioma was diagnosed in 153/210 (73%). Treatment advice was provided for 127 of 171 diagnostic cases (74%) and further investigations suggested for all 35 non-diagnostic cases. 86/210 cases (41%) were invited to participate in a trial, of whom 43/86 (50%) subsequently enrolled. Additional benefits included the avoidance of postmortem examination if the coroner was satisfied with the multidisciplinary team decision. The overall process from referral to outcome dispatch was <2 weeks in 75% of cases. Conclusions This specialist mesothelioma multidisciplinary team meeting was effective at making diagnoses and providing recommendations for further investigations or treatment. The core requirements of a specialist mesothelioma multidisciplinary team meeting were met. The process was timely, with most outcomes returned within 2 weeks of referral.

Medical and oncological management of malignant mesothelioma.

Mesothelioma is an aggressive cancer, for which no curative oncological treatment currently exists. This article outlines the options for managing malignant pleural effusions, describes the developments in chemotherapy over the past 10 years and summarizes the evidence for prophylactic and palliative radiotherapy.

Nutritional management in chyle leaks and chylous effusions

Chyle leaks occur when there is interruption to the lymphatic ducts that transport chyle around the body. The loss of this protein-rich, calorie-rich fluid can cause serious complications including dehydration, malnutrition and immunosuppression. Treatment of chyle leaks depends on the underlying cause, which may be surgical, secondary to malignant invasion or the result of a medical condition. Nutritional support is vital and leads to spontaneous leak closure in many cases. Nutritional management options include total bowel rest with parenteral nutrition, enteral feeding with specialized formula, or oral diet with supplementation. At present there is no consensus regarding which approach is superior. In reality, most patients with chyle leaks are managed with a combination or oral and enteral feeding, but further work is needed to clarify the optimum management strategy.

Recurrence rates in primary spontaneous pneumothorax: a systematic review and meta-analysis

Primary spontaneous pneumothorax (PSP) recurrence rates vary widely in the published literature, with limited data describing the factors that influence recurrence. The aims of this systematic review were to determine an estimation of PSP recurrence rates and describe risk factors for recurrence. A systematic review was conducted of all studies reporting PSP recurrence. Electronic searches were performed to identify English language publications of randomised trials and observational studies. The population was adults with PSP, who underwent conservative management, pleural aspiration or chest drainage. The outcome of interest was recurrence. Articles were screened and data extracted from eligible studies by two reviewers. Of 3607 identified studies, 29 were eligible for inclusion, comprising 13 548 patients. Pooled 1-year and overall recurrence rates were 29.0% (95% CI 20.9–37.0%) and 32.1% (95% CI 27.0–37.2%), respectively. Female sex was associated with increased recurrence (OR 3.03, 95% CI 1.24–7.41), while smoking cessation was associated with a four-fold decrease in risk (OR 0.26, 95% CI 0.10–0.63). I2 for random effects meta-analysis was 94% (p<0.0001), reflecting high heterogeneity between studies. This systematic review demonstrates a 32% PSP recurrence rate, with greatest risk in the first year. Female sex was associated with higher risk, suggesting possible sex-specific pathophysiology. PSP has a 32% recurrence rate, with almost all the risk in the first year. Smoking cessation decreases this risk four-fold. Females may be at higher risk, possibly due to sex-specific pathogenic mechanisms. http://ow.ly/Mty730kPi9z

P12 Exploring the characteristics of patients with mesothelioma who decline chemotherapy: a prospective cohort of 200 patients

Introduction Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis. Treatment options are limited, and pemetrexed and cisplatin chemotherapy is the only intervention shown to extend life. Promising new therapies may provide alternate treatment options in the future. Chemotherapy uptake varies in MPM. Some centres report rates as low as 46% in eligible patients. The aim of this study was to explore the characteristics of patients who declined chemotherapy, and to determine which factors were associated with chemotherapy refusal. Methods Prospective data were collected on all patients diagnosed with MPM in one UK tertiary referral centre. Diagnosis of MPM and eligibility for chemotherapy were determined at the regional MPM multidisciplinary meeting. Patients were followed up until death or censored on 13/7/16. Patient characteristics were compared using chi-squared, Fishers Exact and unpaired T-tests. Kaplan Meier curves were drawn to compare survival between patients who accepted and declined chemotherapy. Logistic regression was used to assess associations between patient characteristics and chemotherapy uptake. Results 200 patients were diagnosed with MPM between 1/3/08 and 8/6/16. 150 (75%) were eligible for chemotherapy. 93/150 (62%) patients received chemotherapy, 46/150 (31%) declined and 11/150 (7.3%) patients did not receive it for other reasons. Patient characteristics are shown in Table 1. The group who declined chemotherapy were older (mean age 74.4 vs 68.4, p < 0.001), with a higher proportion of females (23.9% vs 10.8%, p = 0.041) and fewer patients with performance status (PS) 0 (17.4% vs 43%, p = 0.005). Patients who received chemotherapy had longer median survival (426 days vs 203 days, p = 0.001, HR 0.519, p = 0.015). The factors associated with chemotherapy refusal were age (regression coefficient 0.144, p < 0.001) and PS ≥ 1 (coefficient 1.052, p = 0.027). Conclusion This is the first study to report the characteristics of MPM patients who declined chemotherapy. Significant differences were seen compared with patients who received chemotherapy. Further research is needed to determine whether similar patterns are seen in other centres. Reasons for refusal were not collected, but the association with age and worse performance status may reflect concerns about chemotherapy toxicity. Qualitative research could explore patients’ reasons for refusing chemotherapy. Abstract P12 Table 1 Characteristics of patients who received chemotherapy and patients who declined chemotherapy Receivedchemo Declinedchemo p Total (n = 139) 93 (66.9) 46 (33.1) Gender, n (%)MaleFemale 83 (89.2)10 (10.8) 35 (76.1)11 (23.9) 0.041 Laterality, n (%)Right Left 54 (58.1)39 (41.9) 27 (58.7)19 (41.3) 0.943 Age, mean (SD) 68.4 (6.36) 74.4 (7.35) <0.001 Performance status, n (%)012 40 (43.0)48 (51.6)5 (5.4) 8 (17.4)32 (69.6)6 (13.0) 0.005 Histology, n (%)EpithelioidSarcomatoidBiphasicDesmoplasticNot specified 63 (67.7)15 (16.1)9 (9.7)2 (2.2)4 (4.3) 36 (78.3)6 (13.0)1 (2.2)1 (2.2)2 (4.3) 0.540 IMIG stage, n (%)IIIIIIIVNot documented 28 (30.1)4 (4.3)33 (35.5)16 (17.2)12 (12.9) 15 (32.6)2 (4.3)13 (28.2)8 (17.4)8 (17.4) 0.587 Symptoms, n (%)Asymptomatic Chest painBreathlessnessCoughSystemic symptoms (fatigue, weight loss or sweats) 6 (6.5)37 (41.9)76 (81.7)41 (44.1)38 (41.3) 0 (0)22 (47.8)39 (84.8)18 (39.1)22 (47.8) 0.0780.4700.5500.4990.367 Blood tests, median (IQR)Haemoglobin, g/dL, Neutrophils, x109/LLymphocytes,x109/LAlbumin, g/LNLR 138 (126–150)5.73 (4.80–7.00)1.6 (1.15–2.15)35 (31–38)4.00 (2.73–5.38) 132.5 (121–149)5.84 (4.28–7.00)1.32 (1.00–1.94)34 (30–38)4.18 (3.09–6.38) 0.2630.7290.0760.4560.255 Survival, days, median (IQR)HR (univariable cox proportional hazards)HR (multivariable cox proportional hazards) 426 (290–674)0.4970.519 203 (126–405) 0.0010.0010.015

Commentary: considerations for using the ‘Trials within Cohorts’ design in a clinical trial of an investigational medicinal product

BackgroundThe ‘trials within cohorts’ (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort.Main textTo date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations.We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule.ConclusionWe have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

Physiological predictors of Hypoxic Challenge Testing (HCT) outcomes in Interstitial Lung Disease (ILD)

BACKGROUND Pre-flight risk assessments are currently recommended for all Interstitial Lung Disease (ILD) patients. Hypoxic challenge testing (HCT) can inform regarding the need for supplemental in-flight oxygen but variables which might predict the outcome of HCT and thus guide referral for assessment, are unknown. METHODS A retrospective analysis of ILD patients attending for HCT at three tertiary care ILD referral centres was undertaken to investigate the concordance between HCT and existing predictive equations for prediction of in-flight hypoxia. Physiological variables that might predict a hypoxaemic response to HCT were also explored with the aim of developing a practical pre-flight assessment algorithm for ILD patients. RESULTS A total of 106 ILD patients (69 of whom (65%) had Idiopathic Pulmonary Fibrosis (IPF)) underwent HCT. Of these, 54 (51%) patients (of whom 37 (69%) had IPF) failed HCT and were recommended supplemental in-flight oxygen. Existing predictive equations were unable to accurately predict the outcome of HCT. ILD patients who failed HCT had significantly lower resting SpO2, baseline PaO2, reduced walking distance, FEV1, FVC and TLCO, but higher GAP index than those who passed HCT. CONCLUSIONS TLCO >50% predicted and PaO2 >9.42 kPa were independent predictors for passing HCT. Using these discriminators, a novel, practical pre-flight algorithm for evaluation of ILD patients is proposed.