Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee

Our plain-English summary of Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee, by H.I. Pass, D. Giroux, C. Kennedy, et al (Journal of Thoracic Oncology, 2014).

The study

• Authors: H.I. Pass, D. Giroux, C. Kennedy, E. Ruffini, A.K. Cangir, D. Rice, H. Asamura, D. Waller, J. Edwards, W. Weder, H. Hoffmann, J.P. van Meerbeeck, V.W. Rusch, IASLC Staging Committee and Participating Institutions
• Journal: Journal of Thoracic Oncology
• Published: 2014;9(6):856-64
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure).

Methods: Supplementary prognostic variables were studied in three scenarios: (1) all data available, that is, patient pathologically staged and other CORE variables available (2) only clinical staging available along with CORE variables, and (3) only age, sex, histology, and laboratory parameters are known. Survival was analyzed by Kaplan-Meier, prognostic factors by log rank and stepwise Cox regression modeling after elimination of nonsignificant variables. p value less than 0.05 was significant.

Results: A total of 2141 patients with best tumor, node, metastasis (TNM) stages (pathologic with/without clinical staging) had nonmissing age, sex, histology, and type of surgical procedure. Three prognostic models were defined. Scenario A (all parameters): best pathologic stage, histology, sex, age, type of surgery, adjuvant treatment, white blood cell count (WBC) (≥15.5 or not), and platelets (≥400 k or not) (n = 550). Scenario B (no surgical staging): clinical stage, histology, sex, age, type of surgery, adjuvant treatment, WBC, hemoglobin (<14.6 or not), and platelets (n = 627). Scenario C (limited data): histology, sex, age, WBC, hemoglobin, and platelets (n = 906).

Conclusion: Refinement of these models could define not only the appropriate patient preoperatively for best outcomes after cytoreductive surgery but also stratify surgically treated patients after clinical and pathologic staging who do or do not receive adjuvant therapy.

In plain English

This study analyzed an international registry of patients with malignant pleural mesothelioma assembled by the International Association for the Study of Lung Cancer staging committee. Of 3101 patients diagnosed after 1995, 2141 had been staged and had complete data on age, sex, tumor histology and type of surgery. The authors tested whether further factors predicted survival beyond these core factors. Added to the core model, a history of asbestos exposure (yes or probable, versus no) was associated with worse survival (hazard ratio 1.151, p 0.0344, 1722 patients). So were no adjuvant chemotherapy or radiotherapy, weight loss, chest pain, low hemoglobin, high platelet count and high white blood cell count. Smoking history was not statistically significant. Asbestos exposure was eliminated from the 268-patient all-variable model and was not a candidate in the 550-patient model. In 550 patients with pathologic staging, the final model kept stage, histology, sex, age, surgery type, adjuvant treatment, platelets and white cell count. A model without staging (906 patients) kept histology, sex, age, platelets and white cell count. The authors noted extensive missing data and unstandardized chemotherapy records.

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 an international registry of surgically treated malignant pleural mesothelioma patients (prognostic factor modeling with Cox regression)
• Who was studied: 3101 patients diagnosed with malignant pleural mesothelioma after 1995 (registry period January 4, 1995 to August 18, 2009) from 15 data sources in North America, Europe, Asia and Australia. 2316 were staged, and 2141 had complete data on age, sex, histology and type of surgical procedure. Subsets of 268, 550, 627 and 906 patients were used for specific models.
• Exposure: Not an exposure study. A recorded history of asbestos exposure (yes/probable in 1259, no in 463, no data in 419 of the 2141) was one of several candidate prognostic variables. No fiber types are given.
• Main results:
  • In the CORE model (2141 patients), worse survival was associated with stage III vs I (hazard ratio 1.48), stage IV vs I (1.86), nonepithelioid histology (1.67), male sex (1.27), age 50 to 64 vs under 50 (1.26), age 65 and over vs under 50 (1.34), and palliative vs curative-intent surgery (1.70). Stage II vs I (1.17, p 0.0953) was not significant.
  • Each variable was added to the CORE model separately. Asbestos exposure (yes/probable vs no, 1722 patients) had a hazard ratio of 1.151 (p 0.0344); unadjusted it was 1.211 (p 0.002). No adjuvant therapy (1.551), weight loss (1.581), chest pain (1.306), hemoglobin under 14.6 (1.37), platelets 400 or more (1.767) and white cell count 15.5 or more (1.869) were also associated with worse prognosis.
  • Added to the CORE model, smoking history (802 patients) had a hazard ratio of 1.147 (p 0.113), which was not statistically significant. ECOG performance status, dyspnea and serum LDH were also not significant.
  • In the 268 patients with data on all candidate variables, asbestos exposure among them, the final stepwise model kept best stage, histology, sex, type of surgery, adjuvant treatment, weight loss and white cell count. Asbestos exposure was not retained.
  • In the final model with pathologic staging (550 patients), prognostic variables were pathologic stage, nonepithelioid histology (hazard ratio 1.8), male sex (1.7), age 50 or older (1.61), palliative surgery (1.67), no adjuvant treatment (1.7), platelets 400 or more (1.5) and white cell count 15.5 or more (2.39). Asbestos exposure was not one of the candidate variables evaluated in this model.
  • When clinical rather than pathologic stage was used (627 patients), the final model was similar, except that hemoglobin under 14.6 was also an independent prognostic variable (hazard ratio 1.41, p 0.0051).
  • In the presentation model without staging (906 patients), the final variables were histology (hazard ratio 1.798), sex (1.535), age, platelet count and white cell count. In this model, asbestos exposure added to age, histology and sex had a hazard ratio of 1.104 (p 0.1088), which was not significant.
• The authors' conclusion: The authors concluded that refining these models could help identify, before surgery, the patients likely to do best after cytoreductive surgery. They could also stratify surgically treated patients who do or do not receive adjuvant therapy. The authors described a poor-prognosis phenotype: males older than 50 with nonepithelial histology and elevated platelet and white cell counts.
• Limitations the authors state:
  • Chemotherapy data were not standardized for regimen or timing, and whether it was given before or after surgery could not be determined.
  • There was extensive missing data in this first registry (from 9.7% to 84.4% depending on the variable).
  • The analyses were compromised by the missing data.
  • Performance status may not have separated patients because most surgical patients were ECOG 0 or 1.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, IASLC, Staging, Lung Cancer, Histology, Metastasis, Cytoreductive Surgery, Adjuvant Therapy.

Related studies

• The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation — H. Pass, D. Giroux, et al. (2016)
• The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma — V.W. Rusch, K. Chansky, et al. (2016)
• The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma — D. Rice, K. Chansky, et al. (2016)
• 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)
• Initial analysis of the international association for the study of lung cancer mesothelioma database — V.W. Rusch, D. Giroux, et al. (2012)
• Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group — D. Rice, V. Rusch, et al. (2011)

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