Addition of radiotherapy to surgery and chemotherapy improves survival in localized malignant pleural mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) study

Our plain-English summary of Addition of radiotherapy to surgery and chemotherapy improves survival in localized malignant pleural mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) study, by A.B. Thompson, T.J. Quinn, Z.A. Siddiqui, et al (Lung Cancer, 2020).

The study

• Authors: A.B. Thompson, T.J. Quinn, Z.A. Siddiqui, M.F. Almahariq, I.S. Grills, C.W. Stevens
• Journal: Lung Cancer
• Published: 2020;146:120-126
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a devastating disease with poor survival outcomes for most patients. Optimizing therapeutic approaches is thus vital, but has been hampered by a dearth of randomized trials to guide decision making. We used a population-level database to evaluate the impact of radiotherapy as a component of trimodality therapy on overall survival (OS) in MPM.

Methods: We retrospectively reviewed the SEER Radiation/Chemotherapy database for patients with MPM who received surgery and chemotherapy, with or without radiotherapy. A propensity score-matched analysis with inverse probability of treatment weighting (IPTW) was performed. Weight-adjusted univariate KM analysis was performed and doubly robust, IPTW-adjusted multivariable cox proportional hazards regression modeling was also performed to quantify the effect of radiotherapy on OS in trimodality therapy for MPM.

Results: 1015 patients were identified. 678 patients received surgery and chemotherapy, and 337 patients received trimodality therapy. For patients with localized disease, OS was significantly improved with trimodality therapy (HR 0.56, CI 0.4 - 0.8, p = 0.001), which persisted with IPTW adjustment (HR 0.65, CI 0.49 - 0.95, p = 0.0248). No significant benefit was seen for patients with regional or distant disease. On multivariate analysis, positive predictors of survival after IPTW adjustment were female sex, diagnosis after 2005, and left-sided disease.

Conclusions: These findings support a significant benefit to OS by incorporating radiotherapy as a component of trimodality therapy for patients with localized MPM compared to only surgery and chemotherapy. It does not provide a significant overall survival benefit for patients with regional or metastatic disease.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

This retrospective study used the US Surveillance, Epidemiology, and End Results (SEER) cancer registry. It looked at 1015 patients with malignant pleural mesothelioma who had surgery and chemotherapy. Of these, 678 had only those two treatments and 337 also received radiotherapy, called trimodality therapy. The study did not look at asbestos exposure. The authors used statistical weighting (IPTW) to make the two groups comparable. Across all patients, adding radiotherapy was not linked to significantly longer survival after weighting (hazard ratio for death 0.91, 95% CI 0.79 to 1.04), and weighted median survival was 15 versus 18 months. In patients with localized disease, trimodality therapy was linked to longer survival after weighting (hazard ratio 0.68, CI 0.5 to 0.95, p = 0.025). Median survival was 15 versus 22 months and 5-year survival 5.7% versus 15.6%. No significant benefit was seen in regional or distant disease. The authors concluded that trimodality therapy including radiation is associated with improved survival in localized disease. They noted possible residual confounding, possible registry coding errors, and missing details on chemotherapy type and on radiation dose or intent.

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 population-based cancer registry (SEER), with propensity-score weighting (inverse probability of treatment weighting, IPTW), Cox regression and a landmark analysis
• Who was studied: 1015 patients in the SEER 18 registry (United States) with microscopically confirmed malignant pleural mesothelioma who underwent surgery and received chemotherapy, diagnosed between 1975/1976 and 2016. Of these, 678 had surgery plus chemotherapy and 337 had trimodality therapy.
• Exposure: Treatment, not asbestos: radiotherapy added to surgery and chemotherapy (trimodality therapy), compared with surgery and chemotherapy alone. Asbestos exposure was not studied.
• Main results:
  • All patients, before weighting: trimodality therapy was associated with improved overall survival (HR 0.83, 0.72-0.95, p = 0.008).
  • All patients, after IPTW weighting: trimodality therapy was no longer associated with improved overall survival (HR 0.91, 0.79 to 1.04, p = 0.167). It was also not significant in the doubly robust multivariable model (HR 0.89, CI 0.77 to 1.03, p = 0.1275).
  • All patients, IPTW-adjusted: median overall survival was 15 months with surgery plus chemotherapy versus 18 months with trimodality therapy (not significant).
  • Localized disease, unadjusted: HR 0.56 (CI 0.4-0.8, p = 0.001). Median overall survival was 15 vs. 24 months, 2-year survival 26.1% vs. 48.1%, and 5-year survival 5.9% vs. 21.3% (surgery plus chemotherapy vs. trimodality).
  • Localized disease, after IPTW adjustment: trimodality therapy was associated with improved overall survival (HR 0.68, CI 0.5-0.95, p = 0.025).
  • Localized disease, IPTW-adjusted: median overall survival was 15 vs 22 months, 2-year survival 26.1% vs. 41.1%, and 5-year survival 5.7% vs. 15.6% (surgery plus chemotherapy vs. trimodality).
  • Localized disease, 3-month landmark analysis with IPTW adjustment: HR 0.71, CI 0.5 to 1.0, p = 0.05.
  • After IPTW adjustment, only patients with localized disease showed a statistically significant survival benefit from trimodality therapy. No significant benefit was seen in regional or distant disease.
  • IPTW-adjusted multivariable analysis, positive predictors of survival: female sex (HR 0.74, 0.62-0.89), diagnosis in 2006-2016 (HR 0.7, 0.51-0.96) and left-sided disease (HR 0.86, 0.74-0.99).
  • Negative predictors of survival in the multivariable analysis: age 70 or older (IPTW-adjusted HR 1.73, 1.27-2.36), male sex, and non-epithelioid histology.
• The authors' conclusion: The authors concluded that trimodality therapy including radiation is associated with improved overall survival for patients with localized malignant pleural mesothelioma. They observed no survival advantage in regional or advanced disease.
• Limitations the authors state:
  • Despite IPTW adjustment, residual confounding between the two treatment groups, including from factors not recorded in SEER, remains possible.
  • Coding errors in the SEER database are possible and could affect the results.
  • No details were available on the type of chemotherapy given.
  • No details were available on radiation dose, or on whether radiation was given with adjuvant, salvage or palliative intent.

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: Chemotherapy, Pleural Mesothelioma, Epidemiology, SEER, Trimodality Therapy, Overall Survival, Multivariate Analysis.

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• Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy — S. Bölükbas, C. Manegold, et al. (2011)
• Second-line gemcitabine-based chemotherapy regimens improve overall 3-year survival rate in patients with malignant pleural mesothelioma: a multicenter retrospective study — H. Mutlu, S. Gündüz, et al. (2014)

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