Michael Darby

S17 Pleural Irrigation Trial (PIT): Standard Care Versus Pleural Irrigation, a Randomised Controlled Trial in Patients with Pleural Infection

Background Pleural infection remains common with an increasing incidence. It is associated with a high morbidity and mortality. Despite chest tube drainage and antibiotic therapy up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial but this has never been the tested in the form of a randomised controlled trial. Method Randomised controlled pilot study comparing saline irrigation (250ml normal saline intra-pleurally over one hour, 3 times a day for 3 days) plus best standard care, with best standard care alone, in patients with pleural infection (microbiology positive or pH<7.2 or purulent pleural fluid and clinical infection) requiring chest tube drainage, who had a residual pleural collection on baseline CT thorax. Primary outcome was percentage change in CT pleural volume from day 0 to day 3. Secondary outcomes included referral for surgery, hospital stay and adverse events. Results 47 patients approached, 38 randomised, 3 excluded (drain fell out/no residual fluid on CT/removal of consent). Saline irrigation results in significant reduction in CT pleural collection volume compared to standard care – Irrigation group 29.15% reduction (95% CI 16.2–62) vs Standard care 13.9% (95% CI –4.1–26.3) p<0.04. There was also a significant reduction in the need for thoracic surgery in the irrigation group 9/17 vs 2/18 p=0.01 (OR 9.0, 95% CI 1.56–51.9). No differences were seen in length of hospital stay or fall in inflammatory markers (CPR, WCC and procalcitinin). The safety profile of saline irrigation was good with no serious complications and adverse events did not differ between groups. Conclusion Saline irrigation improves fluid drainage in pleural infection (as measured by volumetric CT), leading to reduction in referral for surgery. No change in hospital stay was noted. This study now needs to be repeated as a large multicentre RCT powered to look at mortality and length of hospital stay.

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma

Purpose The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. Patients and methods 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from 18F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan–Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. Results PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan–Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with 18F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. Conclusions 18F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

S21 A prospective study using serum mesothelin to monitor malignant pleural mesothelioma

Background Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients. Methods This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT scans were performed following the completion of chemotherapy, or from baseline in the BSC group. Changes in mesothelin were correlated with radiological progression and overall survival. Results Forty-one patients with MPM were recruited and followed up for a minimum of 12 months (range 12–21 months). The majority of patients (n=23) received chemotherapy with pemetrexed and cisplatin. Across the cohort a 10% rise in serum mesothelin could predict radiological progression with a sensitivity of 96% (IQR; 79–100) and specificity of 74% (IQR; 50–91) (figure 1). Sensitivity fell to 80% in sarcomatoid only disease. Patients with a rising mesothelin at 6 months had significantly worse overall survival (175 days) compared to stable/falling levels (448 days) (p=0.003). Conclusions This is the first study to assess serum mesothelin’s ability to detect progression of MPM following chemotherapy or during BSC. A 10% rise in serum mesothelin level showed excellent sensitivity at predicting progressive disease. Mesothelin measurement has several advantages over serial CT imaging including reducing hospital visits and cost. Abstract S21 Figure 1

The physiological consequences of different distributions of diffuse pleural thickening on CT imaging

OBJECTIVE Diffuse pleural thickening (DPT) refers to extensive visceral pleural fibrosis with adhesion formation to the parietal pleura obliterating the pleural space. The radiological definition of DPT remains controversial with most of the literature requiring the presence of an obliterated costophrenic angle (CPA) for defining DPT. We conducted a study to investigate the variable distributions of DPT and associated lung function deficit. METHODS 85 patients referred to a pleural clinic with suspected pleural thickening were screened for our study. Data were collected from 37 patients with DPT confirmed on CT by size criteria (≥3 mm thick, ≥5 cm wide and ≥8 cm in length), and 21 controls with pleural plaques but no other pleuroparenchymal pathology. 27 patients were excluded. Groups were matched to age, body mass index and smoking history. RESULTS The percentage of predicted forced vital capacity showed a gradual decline from 98.9% for the control group to 83.5% in the DPT without CPA obliteration group (p < 0.05), to 79.5% in the unilateral DPT group (p < 0.001) and 66.7% in the bilateral group (p < 0.001). Similar reductions were seen in the percentage of predicted total lung capacity in the DPT with no CPA obliteration group and the bilateral DPT group. CONCLUSION Our study shows an incremental reduction in the forced vital capacity and total lung capacity in DPT without CPA obliteration, unilateral and bilateral DPT when compared with a matched control group. Advances in knowledge: Different distributions of DPT including no CPA obliteration can cause respiratory impairment, with bilateral DPT being the worst affected.

S37 Comparison of dynamic contrast enhanced MRI (DCE-MRI) parameters with integrated PET-CT and serum mesothelin in the baseline assessment of malignant pleural mesothelioma

Integrated PET-CT scans and serum mesothelin measurement have shown early promise in predicting prognosis and evaluating treatment response in malignant pleural mesothelioma (MPM) but may be less reliable with sarcomatoid histology or prior talc pleurodesis. Dynamic Contrast Enhanced-MRI (DCE-MRI) with pharmacokinetic analysis is a novel metabolic imaging modality providing a measure of tumour blood flow and angiogenesis. We prospectively examined the relationship between pharmacokinetic parameters on DCE-MRI with PET-CT, serum mesothelin and histological sub-type in MPM patients at diagnosis. Method 30 pre-treatment patients with a histologically proven MPM underwent DCE-MRI and integrated PET-CT and serum mesothelin assay (MESOMARK) at a single visit. SUVmax and total glycolytic volume (TGV) were reported from PET-CT scans with TGV calculated using MIM software version 4.2.2 (MIMvista corp.). Gadolinium washout rate (GWR) on DCE-MRI was defined at a region of interest from a straight line fit to the kinetic curve data (CAD software—ViewForum R6.3 V1L3, Philips Medical Systems) between peak enhancement in the first 2 min and the last data point. Results 70% (21/30) epithelioid and 30% (9/30) sarcomatoid histology. 43% (13/30) had undergone prior talc pleurodesis. Histology did not statistically significantly affect SUVmax, TGV or GWR. Serum mesothelin was significantly greater in the epithelioid group (3.2 nM/l (2.0, 6.3) vs 0.6 nM/l (0.5, 0.8) p<0.001). There was no significant difference in mesothelin, SUVmax, TGV or GWR between talc pleurodesed and non-pleurodesed patients in the whole group, but in the epithelioid sub-group there was a trend to significantly higher TGV with talc pleurodesis (talc: 2799 (1931,11257) no talc: 955.5(146.8,2354) p=0.053) that was not observed with GWR (p=0.4179). While SUVmax strongly correlated to TGV (r=0.725, p<0.001), there was no correlation between GWR and TGV (r=0.203, p=0.282) or between mesothelin levels and any of the imaging values. Conclusion Metabolic imaging has been proposed as an important component of the assessment and management of patients with malignant pleural mesothelioma. Gadolinium washout rate on DCE-MRI may be less sensitive to talc pleurodesis than PET-CT parameters and MRI is a cheaper, more readily available modality that involves shorter patient appointment times, warranting further study in MPM prognostic evaluation and treatment response monitoring.