Duneesha de Fonseka

A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis

Introduction: Malignant pleural mesothelioma (MPM) is a rare cancer with a heterogeneous prognosis. Prognostic models are not widely utilized clinically. Classification and regression tree (CART) analysis examines the interaction of multiple variables with a given outcome. Methods: Between 2005 and 2014, all cases with pathologically confirmed MPM had routinely available histological, clinical, and laboratory characteristics recorded. Classification and regression tree analysis was performed using 29 variables with 18‐month survival as the dependent variable. Risk groups were refined according to survival and clinical characteristics. The model was then tested on an external international cohort. Results: A total of 482 cases were included in the derivation cohort; the median survival was 12.6 months, and the median age was 69 years. The model defined four risk groups with clear survival differences (p < 0.0001). The strongest predictive variable was the presence of weight loss. The group with the best survival at 18 months (86.7% alive, median survival 34.0 months, termed risk group 1) had no weight loss, a hemoglobin level greater than 153 g/L, and a serum albumin level greater than 43 g/L. The group with the worst survival (0% alive, median survival 7.5 months, termed risk group 4d) had weight loss, a performance score of 0 or 1, and sarcomatoid histological characteristics. The C‐statistic for the model was 0.761, and the sensitivity was 94.5%. Validation on 174 external cases confirmed the models ability to discriminate between risk groups in an alternative data set with fair performance (C‐statistic 0.68). Conclusions: We have developed and validated a simple, clinically relevant model to reliably discriminate patients at high and lower risk of death using routinely available variables from the time of diagnosis in unselected populations of patients with MPM.

Prognostication and monitoring of mesothelioma using biomarkers: a systematic review.

Background:Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic.Methods:A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence.Results:Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies.Conclusions:From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival.

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection the alteplase dose assessment for pleural infection therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open‐label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de‐escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open‐label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C‐reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22‐58] to 16% [8‐31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247‐2,984] over 72 h of therapy; P < 0.05) and a reduction in blood C‐reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pleural infection is safe and effective. This regimen should be tested in future randomized controlled trials.

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

Section 3: Clinical features which predict the presence of mesothelioma Recommendations Section 4: Staging systems Recommendation Section 5: Imaging modalities for diagnosing and staging Recommendations Section 6: Pathological diagnosis Recommendations

BTS guideline for the investigation and management of malignant pleural mesothelioma

The full guideline for the investigation and management of malignant pleural mesothelioma is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.

Local Anaesthetic (Medical) Thoracoscopy Services in the UK

Background: Local anaesthetic thoracoscopy (LAT) is an important procedure in the management pathway of patients with pleural effusions, particularly those with suspected malignancy. The last survey evaluating the use and development of LAT services in the UK was conducted over a decade ago. Objectives: We performed a survey of LAT practices in the UK to explore procedural preferences and variations in practice. Methods: The online survey was cascaded via regional pleural specialists to sites performing LAT. One response per site was accepted. Results: Thirty-seven responses were received from England, Scotland and Wales. Most centres have regular access to a dedicated list and a designated area to perform LAT. 97% of the centres have at least 2 trained thoracoscopists. Some variation in practice is seen with patient preparation pre-procedure and medication use. Other procedures, such as insertion of indwelling pleural catheters and adhesiolysis, are not uncommon to be undertaken at the time of LAT. Conclusions: Overall, the results are comparable, excepting some minor variations in patient preparation pre-procedure. We hope that this survey functions as an information resource for centres developing a LAT service or for those considering expansion.

Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial)

Introduction Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%–75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM. Methods Target is a multicentre randomised controlled trial, aiming to recruit 78 patients over a 30-month period, from 10 centres in the UK. Patients will be randomised to either the standard arm which is a second CT-guided biopsy, or the interventional arm, a positron emission tomography-CT scan followed by a targeted CT-guided biopsy. Patients will be followed up for 12 months (patients recruited in the last 6 months of recruitment will have 6 months of follow-up). MPM biomarker mesothelin will be checked at baseline, 6 month and 12 month follow-up appointments where patients are able to attend these appointments. Ethics and dissemination Ethical approval for this trial was granted by the South West—Exeter research and ethics committee (reference number 15/SW/0156). Results of the trial will be published in a peer-reviewed journal and presented at an international conference. Trial registration number ISRCTN14024829; Pre-results.

Nonmalignant Pleural Effusions: A Prospective Study of 356 Consecutive Unselected Patients

Background Pleural effusion secondary to a nonmalignant cause can represent significant morbidity and mortality. Nonmalignant pleural effusion (NMPE) is common, with congestive heart failure representing the leading cause. Despite this, there are limited data on mortality risk and associated prognostic factors. Methods We recruited 782 consecutive patients presenting to a pleural service between March 2008 and March 2015 with an undiagnosed pleural effusion. Further analysis was conducted in 356 patients with NMPE. Pleural biochemical analysis, cytologic analysis, thoracic ultrasonography, and chest radiography were performed. Echocardiography, CT imaging, radiologically guided biopsy, and medical thoracoscopy were undertaken as clinically indicated. Patients were followed for a minimum duration of 12 months, with the final diagnosis decided through independent review by two respiratory consultants. Results Of the 782 patients, 356 were diagnosed with NMPE (46%). These patients had a mean age of 68 years (SD, 17 years) with 69% of them being men. Patients with cardiac, renal, and hepatic failure had 1‐year mortality rates of 50%, 46%, and 25%, respectively. Bilateral effusions (hazard ratio [HR], 3.55; 95% CI, 2.22‐5.68) and transudative effusions (HR, 2.78; 95% CI, 1.81‐4.28) were associated with a worse prognosis in patients with NMPE, with a 57% and 43% 1‐year mortality rate, respectively. Conclusions This is the largest prospectively collected series in patients with NMPE, demonstrating that cases secondary to organ dysfunction have extremely high 1‐year mortality. In addition, the presence of bilateral and transudative effusions is an indicator of increased mortality. Clinicians should be aware of these poor prognostic features and guide management accordingly.

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.

Non-Malignant Pleural Effusions (NMPE)

Background Pleural effusion secondary to a nonmalignant cause can represent significant morbidity and mortality. Nonmalignant pleural effusion (NMPE) is common, with congestive heart failure representing the leading cause. Despite this, there are limited data on mortality risk and associated prognostic factors. Methods We recruited 782 consecutive patients presenting to a pleural service between March 2008 and March 2015 with an undiagnosed pleural effusion. Further analysis was conducted in 356 patients with NMPE. Pleural biochemical analysis, cytologic analysis, thoracic ultrasonography, and chest radiography were performed. Echocardiography, CT imaging, radiologically guided biopsy, and medical thoracoscopy were undertaken as clinically indicated. Patients were followed for a minimum duration of 12 months, with the final diagnosis decided through independent review by two respiratory consultants. Results Of the 782 patients, 356 were diagnosed with NMPE (46%). These patients had a mean age of 68 years (SD, 17 years) with 69% of them being men. Patients with cardiac, renal, and hepatic failure had 1‐year mortality rates of 50%, 46%, and 25%, respectively. Bilateral effusions (hazard ratio [HR], 3.55; 95% CI, 2.22‐5.68) and transudative effusions (HR, 2.78; 95% CI, 1.81‐4.28) were associated with a worse prognosis in patients with NMPE, with a 57% and 43% 1‐year mortality rate, respectively. Conclusions This is the largest prospectively collected series in patients with NMPE, demonstrating that cases secondary to organ dysfunction have extremely high 1‐year mortality. In addition, the presence of bilateral and transudative effusions is an indicator of increased mortality. Clinicians should be aware of these poor prognostic features and guide management accordingly.