Quality Gaps and Comparative Effectiveness of Management Strategies for Recurrent Malignant Pleural Effusions.
ABSTRACT: BACKGROUND:Guidelines for recurrent malignant pleural effusions (MPEs) recommend definitive procedures, such as indwelling pleural catheters (IPCs) or pleurodesis, over repeat thoracentesis. We hypothesized that many patients have multiple thoracenteses rather than definitive procedures and that this results in more procedures and complications. METHODS:Retrospective cohort study using SEER-Medicare data from 2007 to 2011. Patients 66 to 90 years of age with an MPE were included. The primary outcome was whether patients with rapidly recurring MPE, defined as recurrence within 2 weeks of first thoracentesis, received guideline consistent care. Guideline consistent care was defined as a definitive second pleural procedure. RESULTS:Thoracentesis for MPE was performed in 23,431 patients. A second pleural procedure because of recurrence was required in 12,967 (55%). Recurrence was rapid in 7,565 (58%) of the 12,967 patients that had a recurrence. Of the 7,565 patients with rapid recurrence, 1,811 (24%) received guideline consistent care. Definitive pleural procedures compared with repeat thoracentesis resulted in fewer subsequent pleural procedures (0.62 vs 1.44 procedures per patient, respectively; P < .0001), fewer pneumothoraxes (< 0.0037 vs 0.009 pneumothoraxes per patient, respectively; P = .001), and fewer ED procedures (0.02 vs 0.04 ED procedures per patient, respectively; P < .001). Repeat thoracentesis and IPCs resulted in fewer inpatient days compared with chest tube or thoracoscopic pleurodesis (0.013 vs 0.013 vs 0.085 vs 0.097 inpatient days per day of life, respectively; P < .001). CONCLUSIONS:Guideline consistent care using definitive procedures compared with repeat thoracentesis was associated with fewer subsequent procedures and complications; however, pleurodesis resulted in more inpatient days.
Project description:BACKGROUND:Talc pleurodesis (TP) and indwelling pleural catheter (IPC) are used for the management of malignant pleural effusion (MPE). Our meta-analysis was conducted to assess the efficacy and safety of both treatments among patients with MPE. METHODS:We acquired pertinent randomized controlled trials (RCTs) by searching PubMed, ScienceDirect, the Cochrane Library, Scopus, Ovid Medline, Embase, Web of Science, and Google Scholar. The endpoints included survival, pleurodesis rates, total drainage, further pleural interventions, hospital days, symptoms, quality of life (QoL), and complications. RESULTS:We included four high-quality RCTs. Both treatments were effective among patients with MPE and no previous pleurodesis, with comparable survival and equivalent relief of breathlessness. Additionally, the TP group had higher pleurodesis rates, less total drainage, and fewer all-grade complications (including catheter blockage and cellulitis). However, patients in the TP group had more pleural procedures and relatively longer hospital stays. Additionally, no apparent difference was detected in QoL. CONCLUSIONS:TP has better pleurodesis rates, less total drainage, and fewer all-grade complications. However, TP has more pleural procedures and is not feasible for patients with trapped lungs. IPC has fewer further pleural interventions and shorter hospital stays. However, IPC has the nuisance of long-term in situ draining.
Project description:Background:It is known that malignant pleural effusion (MPE) recurs rapidly, in a considerable number of patients. However, some patients do not have MPE recurrence. Since MPE is associated with an average survival of 4-7 months, accurate prediction of prognosis may help recognize patients at higher risk of pleural recurrence, aiming to individualize more intensive treatment strategies. Methods:A prospectively assembled database of cases with pleural effusion treated at a single institution analyzed a subset of patients with symptomatic MPE. Prognostic factors for pleural recurrence were identified by univariable analysis using Kaplan-Meier method and the log-rank test was used for the comparison between the curves. Univariate and multiple Cox regression models were used to evaluate the risk (HR) of recurrence. Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables. Results:A total of 288 patients were included in the analysis. Recurrence-free survival was of 76.6% at 6 months and 73.3% at 12 months. Univariable analysis regarding factors affecting postoperative recurrence was: lymphocytes, platelets, pleural procedure, chemotherapy lines and number of metastases. The independent factors for recurrence-free survival were pleural procedure and chemotherapy lines. Patients who were submitted to pleurodesis had a protective factor for recurrence, with an HR =0.34 (95% CI, 0.15-0.74, P=0.007). On the other hand, patients submitted to the 1st and 2nd line of palliative CT had, respectively, an HR risk = 2.81 (95% CI, 1.10-7.28, P=0.034) and HR =3.23 (95% CI, 1.33-7.84, P=0.010). Conclusions:patients receiving the first or second line of systemic treatment have a higher risk of MPE recurrence when compared to patients who underwent MPE treatment before starting the systemic treatment. The definitive treatment of MPE, such as pleurodesis, was associated with a lower risk of MPE recurrence.
Project description:Malignant pleural effusions (MPE) are frequent consequences of malignant disease and significantly impair the quality of life (QoL) of patients. There are two main options for the palliation of MPE-related symptoms: obliterating the pleural space by pleurodesis to prevent further fluid reaccumulation, or chronically draining the pleural fluid with an indwelling pleural catheter (IPC). There is controversy as to which approach is superior each having advantages and drawbacks. Pleurodesis offers a higher chance of rapid resolution of the pleural effusion with an intervention that is time limited but at the expense of a more invasive procedure, the need for a hospital stay and a higher need for repeat procedures. IPC offers an outpatient solution which is less invasive but at the cost of prolonged catheter drainages and care in a significant portion of patients who will not achieve pleurodesis. Impact on QoL, symptom relief and costs do not appear to be significantly different between the two options. Treatment of MPE should be tailored to the patient's functional status, comorbidities, prognosis and personal preferences as well as local expertise. Hybrid approaches using pleurodesis techniques and IPC concomitantly may come into play in the near future to further improve patient care.
Project description:BACKGROUND AND OBJECTIVE:The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS:Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS:A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P?=?0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P?=?0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P?<?0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P?<?0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P?<?0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION:Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.
Project description:Pleural abrasion has been widely used to control the recurrence of primary spontaneous pneumothorax (PSP). However, controversy still exists regarding the advantages and disadvantages of pleural abrasion compared with other interventions in preventing the recurrence of PSP.The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 15, 2014 to identify randomized controlled trials (RCTs) that compared the effects of pleural abrasion with those of other interventions in the treatment of PSP. The study outcomes included the PSP recurrence rate and the occurrence rate of adverse effects.Mechanical pleural abrasion and apical pleurectomy after thoracoscopic stapled bullectomy exhibited similarly persistent postoperative air leak occurrence rates (p = 0.978) and 1-year PSP recurrence rates (p = 0.821), whereas pleural abrasion led to reduced residual chest pain and discomfort (p = 0.001) and a smaller rate of hemothorax (p = 0.036) than did apical pleurectomy. However, the addition of minocycline pleurodesis to pleural abrasion did not reduce the pneumothorax recurrence rate compared with apical pleurectomy (3.8% for both procedures) but was associated with fewer complications. There was no statistical difference in the pneumothorax recurrence rate between mechanical pleural abrasion and chemical pleurodesis with minocycline on either an intention-to-treat basis (4 of 42 versus 0 of 42, p = 0.12; Fisher exact test) or after exclusions (2 of 40 versus 0 of 42, p = 0.24; Fisher exact test). Pleural abrasion plus minocycline pleurodesis also did not reduce the pneumothorax recurrence rate compared with pleural abrasion alone (p = 0.055). Moreover, pleural abrasion plus minocycline pleurodesis was associated with more intense acute chest pain. The postoperative overall recurrence rate in patients who underwent staple line coverage with absorbable cellulose mesh and fibrin glue was similar to that with mechanical abrasion after thoracoscopic bullectomy (13.8% vs. 14.2%, respectively; p = 0.555), but staple line coverage resulted in less postoperative residual pain than mechanical abrasion (0.4% vs.3.2%; p<0.0001). Pleural abrasion after thoracoscopic wedge resection did not decrease the recurrence of pneumothorax compared with wedge resection alone (p = 0.791), but the intraoperative bleeding and postoperative pleural drainage rates were higher when pleural abrasion was performed.In addition to resulting in the same pneumothorax recurrence rate, thoracoscopic pleural abrasion with or without minocycline pleurodesis is safer than apical pleurectomy in the treatment of PSP. However, minocycline pleurodesis with or without pleural abrasion is not any more effective than pleural abrasion alone. Moreover, additional mechanical abrasion is not safer than additional staple line coverage with absorbable cellulose mesh and fibrin glue after thoracoscopic bullectomy because of increased postoperative pain. Additionally, pleural abrasion after thoracoscopic wedge resection should not be recommended for routine application due to the greater incidence of adverse effects than wedge resection alone. However, further large-scale, well-designed RCTs are needed to confirm the best procedure.
Project description:Malignant pleural effusions (MPEs) remain a common problem, with 40,000 new cases in the United Kingdom each year and up to 250,000 in the United States. Traditional management of MPE usually involves an inpatient stay with placement of a chest drain, followed by the instillation of a pleural sclerosing agent such as talc, which aims to minimise further fluid build-up. Despite a good success rate in studies, this approach can be expensive, time-consuming and inconvenient for patients. More recently, an alternative method has become available in the form of indwelling pleural catheters (IPCs), which can be inserted and managed in an outpatient setting. It is currently unknown whether combining talc pleurodesis with IPCs will provide improved pleural symphysis rates over those of IPCs alone.IPC-PLUS is a patient-blind, multicentre randomised controlled trial (RCT) comparing the combination of talc with an IPC to the use of an IPC alone for inducing pleurodesis in MPEs. The primary outcome is successful pleurodesis at five weeks post-randomisation. This study will recruit 154 patients, with an interim analysis for efficacy after 100 patients, and aims to help to define the future gold standard for outpatient management of patients with symptomatic MPEs.IPC-PLUS is the first RCT to examine the practicality and utility of talc administered via an IPC. The study remains in active recruitment and has the potential to significantly alter how patients requiring pleurodesis for MPE are approached in the future.This trial was registered with Current Controlled Trials (identifier: ISRCTN73255764 ) on 23 August 2012.
Project description:BACKGROUND:Malignant pleural effusion (MPE) causes substantial symptomatic burden in advanced malignancy. Although pleural fluid cytology is a commonly accepted gold standard of diagnosis, its low diagnostic yield is a challenge for clinicians. The aim of this study was to determine whether pro-cathepsin D can serve as a novel biomarker to discriminate between MPE and benign pleural effusion (BPE). METHODS:This study included 81 consecutive patients with exudative pleural effusions who had underwent thoracentesis or pleural biopsy. Pleural fluid and serum were collected as a standard procedure for all individuals at the same time. The level of pro-cathepsin D was measured by the sandwich enzyme-linked immunosorbent assay method. RESULTS:Though there were no significant differences in plasma pro-cathepsin D between the two groups, the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group (0.651 versus 0.590?pg/mL, P?=?0.034). The discriminative power of pleural fluid pro-cathepsin D for diagnosing MPE was moderate, with 81% sensitivity and 53% specificity at a pro-cathepsin D cut-off ?0.596?pg/mL (area under the curve: 0.656). Positive and negative predictive values for MPE were 38 and 89%, respectively, with pro-cathepsin D cut-off value (>?0.596?pg/mL). CONCLUSIONS:The level of pleural fluid pro-cathepsin D was found to be significantly higher in MPE than in BPE. Although results of this study could not support the sole use of pleural fluid pro-cathepsin D to diagnose MPE, pleural fluid pro-cathepsin D can be added to pre-existing diagnostic methods for ruling-in or ruling-out MPE.
Project description:Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.
Project description:Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis.To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion.This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n?=?146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included.Participants were randomized (1:1) to indwelling pleural catheter (n?=?74) or talc pleurodesis (n?=?72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia).The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events.Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P?=?.03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P?<?.001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events).Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion.anzctr.org.au Identifier: ACTRN12611000567921.
Project description:Background: Malignant pleural effusion (MPE) is a common condition that indicates advanced malignancy, incurability and short life expectancy. While MPE incidence is increasing worldwide, prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. Objective: To discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in MPE. To combine clinical, radiologic, and pleural fluid biologic parameters in order to build a score that forecasts survival. Conclusions: The PROMISE score is the first prospectively validated prognostic model for MPE that combines biological and clinical parameters to accurately estimate 3-month mortality.