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      Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score

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          Abstract

          Background

          Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system.

          Methods

          Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated.

          Results

          Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228–549; n=43), 130 days (47–467; n=129) and 44 days (22–77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01).

          Conclusions

          The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

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          Most cited references15

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          A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study.

          Components of the systemic inflammatory response, combined to form inflammation-based prognostic scores (modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI), Prognostic Nutritional Index (PNI)) have been associated with cancer specific survival. The aim of the present study was to compare the prognostic value of these scores. Patients (n=27,031) who had an incidental blood sample taken between 2000 and 2007 for C-reactive protein, albumin, white cell, neutrophil, lymphocyte and platelet counts, as well as a diagnosis of cancer (Scottish Cancer Registry) were identified. Of this group 8759 patients who had been sampled within two years following their cancer diagnosis were studied. On follow up, there were 5163 deaths of which 4417 (86%) were cancer deaths. The median time from blood sampling to diagnosis was 1.7 months. An elevated mGPS, NLR, PLR, PI and PNI were predictive of a reduced cancer specific survival independent of age, sex and deprivation and tumour site (all p<0.001). The area under the receiver operator curves was greatest for mGPS and PI. Specifically, in colorectal cancer, an elevated mGPS and PI were predictive of a reduced cancer specific survival independent of age, sex, deprivation and tumour stage (both p<0.001). The results of the present study show that systemic inflammation-based scores, in particular the mGPS and PI, have prognostic value in cancer independent of tumour site. Based on the present results and the existing validation literature, the mGPS should be included in the routine assessment of all patients with cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy.

            Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients. Patients with MM who had systemic therapy at participating institutes were studied. Potential prognostic factors such as age, gender, performance status, histologic subtype, and baseline laboratory parameters, including NLR, were analyzed. Overall survival from commencement of therapy was determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed with significant factors (P ≤ 0.05) to determine their independent effect. A total of 173 MM patients undergoing systemic therapy including 119 patients receiving first-line therapy and 54 patients receiving second- or third-line therapy were included in this retrospective evaluation. Forty-two percent of patients had an elevated NLR at baseline. The following variables were predictive of survival: female gender (P = 0.044), epithelioid histologic subtype (P < 0.001), baseline white blood cell count less than 8.3 × 10⁹/L (P = 0.008), baseline platelet count 400 × 10⁹/L or less (P = 0.05), and NLR of 5 or less (P < 0.001). After multivariate analysis, histologic epithelioid subtype [hazard ratio (HR) = 2.0; 95% confidence interval (CI) = 1.3-2.9; P = 0.001], and NLR less than 5 (HR = 2.7; 95% CI = 1.8-3.9; P < 0.001) remained independent predictors. The 1-year survival rate was 60% versus 26%, whereas the 2-year survival rate was 34% versus 10% for NLR less than 5 and 5 or greater, respectively. In the separate analyses of chemotherapy-naive and previously treated patient groups, NLR was an independent predictor of survival in both groups. Our results indicate that NLR is an independent predictor of survival for patients with MM undergoing systemic therapy. ©2010 AACR.
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              Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B.

              To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B (CALGB). Between June 1984 and September 1994, 337 patients with malignant mesothelioma and no prior chemotherapy were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels. The eligibility criteria for all studies were virtually identical. Patient characteristics include the following: age older than 60 years (63%); male (83%); performance status (PS) of 0 or 1 (81%); chest pain (60%); definite asbestos exposure (62%); >5% weight loss (41%); and pleural involvement (94%). Median survival time (MST) for the 10 treatment regimens ranged from 3.9 to 9.8 months (overall=7.2; 95% confidence interval [CI], 6.5 to 8.3), with 1-year survival between 14% and 50% (overall=27%; 95% CI, 23 to 33%). Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics. Univariate analyses show that patients with poor Eastern Cooperative Oncology Group PS, chest pain, dyspnea, platelet count (PLT) >400,000/microL, weight loss, serum lactate dehydrogenase (LDH) level >500 IU/L, pleural involvement, low hemoglobin (HGB) level, high WBC count, and increasing age over 75 years have a worse prognosis. With decreasing risk ratio, multivariate Cox analyses showed that pleural involvement, LDH >500 IU/L, poor PS, chest pain, PLT >400,000/microL, nonepithelial histology, and increasing age older than 75 years jointly predict poor survival. PS was the most important prognostic split in the regression tree. Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST (2-year survival) of 13.9 (38%) in 36 patients, 9.5 (21%) in 36 patients, 9.2 (10%) in 146 patients, 6.5 (3%) in 33 patients, 4.4 (0%) in 73 patients, and 1.4 (0%) in 13 patients (p or =14.6. The worst survival (MST= 1.4 months) occurred for patients with PS= 1/2 and WBC > or =15.6/microL.
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                Author and article information

                Journal
                Thorax
                Thorax
                thoraxjnl
                thorax
                Thorax
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0040-6376
                1468-3296
                December 2014
                6 August 2014
                : 69
                : 12
                : 1098-1104
                Affiliations
                [1 ]Academic Respiratory Unit, University of Bristol , Bristol, UK
                [2 ]North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust , Bristol, UK
                [3 ]Pragmatic Clinical Trials Unit, Queen Mary University of London , London, UK
                [4 ]Thoracic Oncology, The Netherlands Cancer Institute, Antonie van Leeuwenhoek Hospital , Amsterdam, The Netherlands
                [5 ]Respiratory Department, Sir Charles Gairdner Hospital , Perth, Australia
                [6 ]Centre for Asthma, Allergy & Respiratory Research, School of Medicine & Pharmacology, University of Western Australia , Perth, Australia
                Author notes
                [Correspondence to ] Dr Nick A Maskell, Academic Respiratory Unit, Second Floor, Learning and Research Building, Southmead Hospital, University of Bristol, Bristol BS10 5NB, UK; nick.maskell@ 123456bristol.ac.uk
                Article
                thoraxjnl-2014-205285
                10.1136/thoraxjnl-2014-205285
                4251306
                25100651
                d527ae4c-d302-40d8-978f-88e58e3c5ba7
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 17 February 2014
                : 1 July 2014
                : 17 July 2014
                Categories
                1506
                Lung Cancer
                Original article
                Custom metadata
                unlocked

                Surgery
                pleural disease,lung cancer,mesothelioma
                Surgery
                pleural disease, lung cancer, mesothelioma

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