Skip to main content

The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma

Abstract

Background

Pleural mesothelioma is a rare but aggressive form of cancer. Local recurrence represents the majority of treatment failures and overall survival (OS) outcomes remain dismal. Adding locoregional treatment with radiotherapy after surgical resection has been considered but its role remains uncertain.

Objective

The purpose of this study was to evaluate the outcomes of adjuvant radiation therapy (RT) for patients with malignant pleural mesothelioma.

Methods

The National Cancer Data Base (NCDB) was queried (2004–2013) for patients with malignant mesothelioma. Patients were divided into three groups: observation, surgery alone, and surgery followed by adjuvant RT. Statistics included Fisher’s exact or Chi square tests to analyze categorical proportions between groups, Kaplan–Meier analysis to evaluate OS, and Cox proportional hazards modeling to determine variables associated with OS. Propensity matching was performed to make comparisons between homogenous groups.

Results

Overall, the surgery plus radiotherapy group had a higher median survival (21.4 months) compared with surgery alone (16.59 months) [p < 0.001]. RT was more likely to be delivered after extrapleural pneumonectomy than with lung-sparing surgical approaches. On multivariable analysis, receipt of surgery plus radiotherapy, chemotherapy administration, and higher socioeconomic status were associated with improved OS (p < 0.0001). After propensity matching, receipt of surgery plus radiotherapy and chemotherapy administration were still associated with improved OS (p < 0.05).

Conclusions

In the treatment of malignant pleural mesothelioma, adjuvant radiotherapy after surgical intervention was associated with improved OS. This study is the largest study of adjuvant radiotherapy to date, and our findings highlight the need for additional prospective data.

This is a preview of subscription content, access via your institution.

References

  1. Matsuo Y, Shibuya K, Okubo K, et al. Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma. Acta Oncol. 2017;56(7):957–962.

    Article  PubMed  Google Scholar 

  2. Robinson BWS, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366(9483):397–408.

    Article  CAS  PubMed  Google Scholar 

  3. Okubo K, Sonobe M, Fujinaga T, et al. Survival and relapse pattern after trimodality therapy for malignant pleural mesothelioma. Gen Thorac Cardiovasc Surg. 2009;57(11):585–590.

    Article  PubMed  Google Scholar 

  4. Kristensen CA, Nøttrup TJ, Berthelsen AK, et al. Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma. Radiother Oncol. 2009;92(1):96–99.

    Article  PubMed  Google Scholar 

  5. Rice DC, Smythe WR, Liao Z, et al. Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2007;69(2):350–357.

    Article  PubMed  Google Scholar 

  6. Taioli E, Wolf AS, Camacho-Rivera M, et al. Determinants of survival in malignant pleural mesothelioma: a surveillance, epidemiology, and end results (SEER) study of 14,228 patients. PLoS One. 2015;10(12):e0145039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohri N, Taioli E, Liu B, et al. Radiation therapy for localized malignant pleural mesothelioma: a propensity score-matched analysis of the National Cancer Data Base. J Radiat Oncol. 2017;6(3):265–272.

    Article  Google Scholar 

  8. Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15(3):683–690.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bott MJ, Patel AP, Verma V, et al. Patterns of care in hilar node-positive (N1) non-small cell lung cancer: a missed treatment opportunity? J Thorac Cardiovasc Surg. 2016;151(6):1549–1558.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Haque W, Verma V, Butler EB, Teh BS. Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as part of multimodal management of low grade glioma. J Neurooncol. 2017;133(2):369–375.

    Article  PubMed  Google Scholar 

  11. Haque W, Verma V, Butler EB, Teh BS. Definitive chemoradiation at high volume facilities is associated with improved survival in glioblastoma. J Neurooncol. 2017;135(1):173–181.

    Article  PubMed  Google Scholar 

  12. Haque W, Verma V, Fakhreddine M, Hatch S, Butler EB, Teh BS. Addition of chemotherapy to definitive radiotherapy for IB1 and IIA1 cervical cancer: analysis of the National Cancer Data Base. Gynecol Oncol. 2017;144(1):28–33.

    Article  PubMed  Google Scholar 

  13. Haque W, Lewis GD, Verma V, Darcourt JG, Butler EB, Teh BS. The role of adjuvant chemotherapy in locally advanced bladder cancer. Acta Oncol. 2018;57(4):509–515.

    Article  PubMed  Google Scholar 

  14. Haque W, Verma V, Lewis GD, Lo SS, Butler EB, Teh BS. Utilization of radiotherapy and stereotactic body radiation therapy for renal cell cancer in the USA. Futur Oncol. 2018;14(9):819–827.

    Article  CAS  Google Scholar 

  15. Fennell DA, Parmar A, Shamash J, et al. Statistical validation of the EORTC prognostic model for malignant pleural mesothelioma based on three consecutive phase II trials. J Clin Oncol. 2005;23(1):184–189.

    Article  PubMed  Google Scholar 

  16. Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol. 1998;16(1):145–152.

    Article  CAS  PubMed  Google Scholar 

  17. Rosenzweig KE, Fox JL, Zelefsky MJ, Raben A, Harrison LB, Rusch VW. A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma. Brachytherapy. 2005;4(1):30–33.

    Article  PubMed  Google Scholar 

  18. Rusch VW, Rosenzweig K, Venkatraman E, et al. A phase II trial of surgical resection and adjuvant highdose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2001;122(4):788–795.

    Article  CAS  PubMed  Google Scholar 

  19. Allen AM, Czerminska M, Jänne PA, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys. 2006;65(3):640–645.

    Article  PubMed  Google Scholar 

  20. Chi A, Liao Z, Nguyen NP, et al. Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma. J Thorac Oncol. 2011;6(6):1132–1141.

    Article  PubMed  Google Scholar 

  21. Patel PR, Yoo S, Broadwater G, et al. Effect of increasing experience on dosimetric and clinical outcomes in the management of malignant pleural mesothelioma with intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2012;83(1):362–368.

    Article  PubMed  Google Scholar 

  22. Tonoli S, Vitali P, Scotti V, et al. Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series. Radiother Oncol. 2011;101(2):311–315.

  23. Ahamad A, Stevens CW, Smythe WR, et al. Intensity-modulated radiation therapy: A novel approach to the management of malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003;55(3):768–775.

    Article  PubMed  Google Scholar 

  24. Buduhan G, Menon S, Aye R, Louie B, Mehta V, Vallières E. Trimodality Therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2009;88(3):870–876.

    Article  PubMed  Google Scholar 

  25. Du K, Both S, Friedberg J. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma. Cancer Biol Ther. 2010;10(5):425–429.

    Article  CAS  PubMed  Google Scholar 

  26. Verma V, Ahern CA, Berlind CG, et al. National Cancer Database report on pneumonectomy versus lung-sparing surgery for malignant pleural mesothelioma. J Thorac Oncol. 2017;12(11):1704–1714.

    Article  PubMed  Google Scholar 

  27. Batirel HF, Metintas M, Caglar HB, et al. Adoption of pleurectomy and decortication for malignant mesothelioma leads to similar survival as extrapleural pneumonectomy. J Thorac Cardiovasc Surg. 2016;151(2):478–484.

    Article  PubMed  Google Scholar 

  28. Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135(3):620–626.

  29. Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer. 2014;83(2):240–245.

    Article  PubMed  Google Scholar 

  30. Aisner DL, Bauman J, Chase Cancer Center Joe Chang FY, et al. NCCN guidelines panel disclosures-Farber/Brigham and Women’s Cancer Center NCCN guidelines version 2.2018 Malignant Pleural Mesothelioma. 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf. Accessed 18 Mar 2018.

  31. Scherpereel A, Astoul P, Baas P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J. 2010;35(3):479–495.

    Article  CAS  PubMed  Google Scholar 

  32. Rosenzweig KE, Zauderer MG, Laser B, et al. Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2012;83(4):1278–1283.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Minatel E, Trovo M, Bearz A, et al. Radical radiation therapy after lung-sparing surgery for malignant pleural mesothelioma: survival, pattern of failure, and prognostic factors. Int J Radiat Oncol Biol Phys. 2015;93(3):606–613.

    Article  PubMed  Google Scholar 

  34. Rimner A, Zauderer MG, Gomez DR, et al. Phase II study of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) as part of lung-sparing multimodality therapy in patients with malignant pleural mesothelioma. J Clin Oncol. 2016;34(23):2761–2768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

John H. Lee Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bin S. Teh MD.

Ethics declarations

Disclosure

Gary D. Lewis, Shraddha M. Dalwadi, Andrew Farach, E. Brian Butler, and Bin S. Teh declare that no conflicts of interest exist.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 14 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lewis, G.D., Dalwadi, S.M., Farach, A. et al. The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma. Ann Surg Oncol 26, 1879–1885 (2019). https://doi.org/10.1245/s10434-019-07235-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-07235-9