Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales

Our plain-English summary of Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales, by A. Linton, N. Pavlakis, R. O'Connell, et al (British Journal of Cancer, 2014).

The study

• Authors: A. Linton, N. Pavlakis, R. O'Connell, M. Soeberg, S. Kao, S. Clarke, J. Vardy, N. van Zandwijk
• Journal: British Journal of Cancer
• Published: 2014;111(9):1860-9
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.

Methods: All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).

Results: We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%).

Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).

Conclusions: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.

In plain English

This study examined 910 people with malignant pleural mesothelioma who registered with the New South Wales Dust Diseases Board in 2002–2009 and were compensated for occupational asbestos exposure, looking for factors linked to survival. Median survival was 10.0 months. In an adjusted analysis of 557 patients, shorter survival was associated with age over 70, male sex, non-epithelioid tumour type (hazard ratio 2.00, 95% CI 1.62 to 2.48), tumours negative for the marker calretinin (hazard ratio 2.13, 95% CI 1.50 to 3.02), high platelet counts, low haemoglobin and higher neutrophil–lymphocyte ratio. The roughly 6% who had extrapleural pneumonectomy, a radical operation, had a median survival of 24.7 months versus 9.5 months for others. Patients were not randomly assigned to surgery. About one in four patients lived at least 20 months; a third of these had neither chemotherapy nor radical surgery. The authors concluded that calretinin was strongly associated with survival and that this surgery and pemetrexed-based chemotherapy seemed capable of producing a survival benefit. They also built a risk score, which they said needs testing in a separate group.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of a compensation-board database of patients with malignant pleural mesothelioma, assessing prognostic factors (Kaplan–Meier and Cox regression) and developing a risk score (Prognostic Index)
• Who was studied: 910 patients with malignant pleural mesothelioma who registered with the NSW Workers' Compensation Dust Diseases Board between 1 January 2002 and 31 December 2009. They were drawn from 1121 registered patients after excluding those living or treated outside NSW, primary peritoneal cases and those lacking clinical information. Mortality was followed up to 27 June 2012. The authors estimated that Board registrants are about 70% of NSW Cancer Registry mesothelioma cases. Patients were 90% male, with a median age of 72 at diagnosis. Data from 557 patients were included in the multivariate analyses.
• Exposure: Occupational asbestos exposure in NSW, which was the basis for compensation. Fiber types were not reported. Years of exposure were estimated from occupational history and age at first exposure: median age at first exposure 18 years, median cumulative exposure 24 years. Exposure duration was not clearly associated with survival (log-rank P = 0.22). The main factors studied were patient, tumour, blood-test and treatment characteristics.
• Main results:
  • Median survival for the whole study population was 10.0 months from diagnosis, ranging from 0 to 123.6 months.
  • Median survival was 13.4 months for patients with epithelioid subtype, compared with 7.2 months (biphasic) and 5.4 months (sarcomatoid); p less than 0.001.
  • Data from 557 patients were included in the multivariate analyses.
  • In multivariate analysis (557 patients), age over 70 and male sex were associated with poorer survival. ECOG performance status was not an independent prognostic factor.
  • In multivariate analysis, tumours negative for calretinin were associated with about twice the mortality risk of calretinin-positive tumours (HR 2.13, 95% CI 1.50 to 3.02).
  • In multivariate analysis, non-epithelioid subtypes had about twice the mortality risk of epithelioid histology (HR 2.00; 95% CI 1.62 to 2.48).
  • In multivariate analysis, two blood-test results were associated with increased risk of death: platelet count of 400 or more (HR 1.39; 95% CI 1.13 to 1.70) and low haemoglobin (HR 1.27; 95% CI 1.02 to 1.58).
  • Higher neutrophil–lymphocyte ratio, analysed as a continuous variable, was independently associated with poorer prognosis (HR 1.04; 95% CI 1.02 to 1.06).
  • Patients who had extrapleural pneumonectomy (6.4% of the study population) had a median survival of 24.7 months from diagnosis. Patients who did not have radical surgery had a median survival of 9.5 months.
  • Treating surgery as a time-dependent variable, unadjusted for other factors, extrapleural pneumonectomy was associated with lower mortality (HR 0.41, 95% CI 0.30 to 0.56; p less than 0.001).
  • A separate analysis of 721 patients alive at 4 months also found a survival advantage for extrapleural pneumonectomy (HR 0.42, 95% CI 0.29 to 0.60; p less than 0.001), independent of other variables.
  • Median survival from diagnosis by chemotherapy received: 15.8 months with pemetrexed-based chemotherapy, 10.4 months with other regimens (P = 0.017), and 6.6 months with no chemotherapy.
  • In the multivariable table (557 patients), receiving pemetrexed compared with no chemotherapy had a hazard ratio of 0.94 (95% CI 0.78 to 1.13; P = 0.49), which was not statistically significant. Surgical intervention had a hazard ratio of 0.61 (95% CI 0.42 to 0.89; P = 0.011).
  • About one in four patients survived at least 20 months, twice the median. Of these long survivors, 66% received chemotherapy and 16% had radical surgery.
  • A third of the long survivors received neither chemotherapy nor radical surgery.
  • The new risk score had a C statistic of 0.747, which the authors described as moderate performance. Median survival was 6.6 months for its 'high-risk' group and 16.6 months for its 'low-risk' group. In the authors' comparison, it separated good and poor prognosis better than the EORTC score.
• The authors' conclusion: The authors concluded that calretinin expression is strongly associated with survival. They also concluded that extrapleural pneumonectomy and pemetrexed-containing chemotherapy seem capable of producing a survival benefit that remains after accounting for 'good prognosis' factors.
• Limitations the authors state:
  • Stage was estimated from CT scans rather than PET or surgical staging. More patients were classed as early stage than in previous studies, so stage was left out of the multivariate analysis and the risk score.
  • The calretinin-negative group was small: 8.6% of patients tested.
  • The analysis starting at 4 months was based on non-randomised comparisons and included only patients who survived to 4 months.
  • The authors could not compare their score with the CALGB model because key variables were missing from the retrospective records.
  • The risk score has not been validated and needs testing in a large independent series of patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Histology, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Calretinin, Chemotherapy.

Related studies

• Validation of prognostic factors in malignant pleural mesothelioma: a retrospective analysis of data from patients seeking compensation from the New South Wales Dust Diseases Board — S.C. Kao, J. Vardy, et al. (2013)
• Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes — A. Linton, M. Soeberg, et al. (2017)
• Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy — S.C. Kao, S. Klebe, et al. (2011)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Patterns in the incidence, mortality and survival of malignant pleural and peritoneal mesothelioma, New South Wales, 1972-2009 — M.J. Soeberg, N. Creighton, et al. (2016)
• PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy — B.K. Bitanihirwe, M. Meerang, et al. (2014)

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