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Annals of Surgical Oncology

, Volume 26, Issue 8, pp 2357–2366 | Cite as

Management of Malignant Pleural Mesothelioma in the Elderly Population

  • Vivek Verma
  • Rodney E. Wegner
  • Ethan B. Ludmir
  • Shaakir Hasan
  • Athanasios Colonias
  • Surbhi Grover
  • Joseph S. Friedberg
  • Charles B. SimoneIIEmail author
Thoracic Oncology

Abstract

Background

The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72 years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients.

Methods

The National Cancer Database was queried for patients aged ≥ 80 years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan–Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients.

Results

Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p < 0.001). Differences between all groups persisted following propensity matching (all comparisons p < 0.05). For the 8% of patients who underwent specified definitive surgery (95% of whom received pleurectomy/decortication), 30- and 90-day mortality rates were 11.0% and 28.5%, respectively. The median length of postoperative hospitalization was 6 days, with 30-day readmission occurring in 7.5% of patients.

Conclusions

The majority of elderly MPM patients in the US are observed, which was associated with poorer OS than chemotherapy and/or surgery. Although highly selected surgery/chemotherapy patients were associated with the longest OS, given the high biases in database studies and high perioperative mortality rates, careful patient selection for combined modality approaches in this population is imperative.

Notes

Acknowledgments

This study has not been previously presented or published elsewhere, either in part or in full.

Author Contributions

VV takes responsibility for, and is the guarantor of, the content of this manuscript, including the data and analysis. VV, REW, EBL, SH, AC, SG, JSF, and CBS contributed substantially to the study design, data analysis and interpretation, and the writing of this manuscript.

Funding

No research support was received for this study.

Disclosure

Vivek Verma, Rodney E. Wegner, Ethan B. Ludmir, Shaakir Hasan, Athanasios Colonias, Surbhi Grover, Joseph S. Friedberg, and Charles B. Simone II declare they have no conflicts of interest.

Supplementary material

10434_2019_7351_MOESM1_ESM.tif (21 kb)
Supplementary Fig. 1 Comparison of overall survival between treatment paradigms in patients < 80 years of age (TIFF 20 kb)

References

  1. 1.
    National Comprehensive Cancer Network. Malignant pleural mesothelioma. Version 2.2018. https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf. Accessed 1 Nov 2018.
  2. 2.
    Bovolato P, Casadio C, Bille A, et al. Does surgery improve survival of patients with malignant pleural mesothelioma?: a multicenter retrospective analysis of 1365 consecutive patients. J Thorac Oncol. 2014;9:390–6.CrossRefGoogle Scholar
  3. 3.
    Sugarbaker DJ, Gill RR, Yeap BY, et al. Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection. J Thorac Cardiovasc Surg. 2013;145:955–63.CrossRefGoogle Scholar
  4. 4.
    Lang-Lazdunski L, Bille A, Belcher E, et al. Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma. J Thorac Oncol. 2011;6:1746–52.CrossRefGoogle Scholar
  5. 5.
    Zhu TC, Liang X, Kim MM, et al. An IR navigation system for pleural PDT. Front Phys. 2015;3:9.CrossRefGoogle Scholar
  6. 6.
    Simone CB 2nd, Cengel KA. Photodynamic therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol. 2014;41:820–30.CrossRefGoogle Scholar
  7. 7.
    Damhuis RA, Khakwani A, De Schutter H, et al. Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England. Lung Cancer. 2015;89:212–7.CrossRefGoogle Scholar
  8. 8.
    Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–44.CrossRefGoogle Scholar
  9. 9.
    Treasure T, Lang-Lazdunski L, Waller D, et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol. 2011;12:763–72.CrossRefGoogle Scholar
  10. 10.
    Stahel RA, Riesterer O, Xyrafas A, et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol. 2015;16:1651–8.CrossRefGoogle Scholar
  11. 11.
    Marinaccio A, Binazzi A, Marzio DD, et al. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer. 2012;130:2146–54.CrossRefGoogle Scholar
  12. 12.
    Boffetta P, Malvezzi M, Pira E, Negri E, La Vecchia C. International analysis of age-specific mortality rates from mesothelioma on the basis of the international classification of diseases, 10th revision. J Glob Oncol. 2018;4:1–15.CrossRefGoogle Scholar
  13. 13.
    Bilimoria K, Stewart A, Winchester D, Ko C. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15:683–90.CrossRefGoogle Scholar
  14. 14.
    Ho DE, Kosuke I, King G, Stuart EA. MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw. 2011;42:1–28.CrossRefGoogle Scholar
  15. 15.
    Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10:150–61.CrossRefGoogle Scholar
  16. 16.
    Verma V, Ahern CA, Berlind CG, et al. Survival by histologic subtype of malignant pleural mesothelioma and the impact of surgical resection on overall survival. Clin Lung Cancer. 2018;19:e901–12.CrossRefGoogle Scholar
  17. 17.
    Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg. 2004;128:138–46.CrossRefGoogle Scholar
  18. 18.
    Krug LM, Pass HI, Rusch VW, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27:3007–13.CrossRefGoogle Scholar
  19. 19.
    Van Schil PE, Baas P, Gaafar R, et al. Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. Eur Respir J. 2010;36:1362–9.CrossRefGoogle Scholar
  20. 20.
    Bovolato P, Casadio C, Bille A, et al. Does surgery improve survival of patients with malignant pleural mesothelioma?: A multicenter retrospective analysis of 1365 consecutive patients. J Thorac Oncol. 2014;9:390–6.CrossRefGoogle Scholar
  21. 21.
    Linton A, Pavlakis N, O’Connell R, et al. Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales. Br J Cancer. 2014;111:1860–9.CrossRefGoogle Scholar
  22. 22.
    Lauk O, Hoda MA, de Perrot M, et al. Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 mesothelioma patients from three high-volume institutions. Ann Thorac Surg. 2014;98:1748–54.CrossRefGoogle Scholar
  23. 23.
    McMillan RR, Berger A, Sima CS, et al. Thirty-day mortality underestimates the risk of early death after major resections for thoracic malignancies. Ann Thorac Surg. 2014;98:1769–75.CrossRefGoogle Scholar
  24. 24.
    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;151:478–84.CrossRefGoogle Scholar
  25. 25.
    Sharkey AJ, Tenconi S, Nakas A, Waller DA. The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication. Eur J Cardiothorac Surg. 2016;49:1632–41.CrossRefGoogle Scholar
  26. 26.
    Sharkey AJ, Bilancia R, Tenconi S, Nakas A, Waller DA. Extended pleurectomy decortication for malignant pleural mesothelioma in the elderly: the need for an inclusive yet selective approach. Interact CardioVasc Thorac Surg. 2017;25:696–702.CrossRefGoogle Scholar
  27. 27.
    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;12:1704–14.CrossRefGoogle Scholar
  28. 28.
    Williams T, Duraid H, Watson S, et al. Extended pleurectomy and decortication for malignant pleural mesothelioma is an effective and safe cytoreductive surgery in the elderly. Ann Thorac Surg. 2015;100:1868–74.CrossRefGoogle Scholar
  29. 29.
    Ceresoli GL, Castagneto B, Zucali PA, et al. Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials. Br J Cancer. 2008;99:51–6.CrossRefGoogle Scholar
  30. 30.
    Friedberg JS, Mick R, Culligan M, et al. Photodynamic therapy (PDT) and the evolution of a lung sparing surgical treatment for mesothelioma. Ann Thorac Surg. 2011;91:1738–45.CrossRefGoogle Scholar
  31. 31.
    Friedberg JS, Simone CB 2nd, Culligan MJ, et al. Extended pleurectomy-decortication-based treatment for advanced stage epithelial mesothelioma yielding a median survival of nearly three years. Ann Thorac Surg. 2017;103:912–9.CrossRefGoogle Scholar
  32. 32.
    Verma V, Ahern CA, Berlind CG, et al. Facility volume and postoperative outcomes for malignant pleural mesothelioma: a National Cancer Data Base analysis. Lung Cancer. 2018;120:7–13.CrossRefGoogle Scholar
  33. 33.
    Verma V, Ahern CA, Berlind CG, et al. Treatment of malignant pleural mesothelioma with chemotherapy preceding versus following surgical resection. J Thorac Cardiovasc Surg. 2019;157(2):758–766.e1.CrossRefGoogle Scholar
  34. 34.
    Chow WB, Rosenthal RA, Merkow RP, et al. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215:453–66.CrossRefGoogle Scholar
  35. 35.
    Mohanty S, Rosenthal RA, Russell MM, et al. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2016;222:930–47.CrossRefGoogle Scholar
  36. 36.
    Yang CJ, Yan BW, Meyerhoff RR, et al. Impact of age on long-term outcomes of surgery for malignant pleural mesothelioma. Clin Lung Cancer. 2016;17:419–26.CrossRefGoogle Scholar
  37. 37.
    Shaaban SG, Verma V, Choi JI, et al. Utilization of intensity-modulated radiation therapy for malignant pleural mesothelioma in the United States. Clin Lung Cancer. 2018;19:e685–92.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Vivek Verma
    • 1
  • Rodney E. Wegner
    • 1
  • Ethan B. Ludmir
    • 2
  • Shaakir Hasan
    • 1
  • Athanasios Colonias
    • 1
  • Surbhi Grover
    • 3
  • Joseph S. Friedberg
    • 4
  • Charles B. SimoneII
    • 5
    • 6
    Email author
  1. 1.Department of Radiation OncologyAllegheny General HospitalPittsburghUSA
  2. 2.Department of Radiation OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Radiation OncologyUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Surgery, Division of Thoracic SurgeryUniversity of Maryland Medical CenterBaltimoreUSA
  5. 5.Department of Radiation OncologyUniversity of Maryland School of MedicineBaltimoreUSA
  6. 6.New York Proton CenterNew YorkUSA

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