Skip to main content
SpringerLink
Log in

Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM.

Methods

We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes.

Results

Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001).

Conclusions

Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Munkholm-Larsen S, Cao CQ, Yan TD. Malignant peritoneal mesothelioma. World J Gastrointest Surg. 2009;1:38–48.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Price B, Ware A. Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. Am J Epidemiol. 2004;159:107–12.

    Article  PubMed  Google Scholar 

  3. Yan TD, Welch L, Black D, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol. 2007;18:827–34.

    Article  CAS  PubMed  Google Scholar 

  4. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, 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.

    Article  CAS  PubMed  Google Scholar 

  5. van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005;23:6881–9.

    Article  PubMed  Google Scholar 

  6. Janne PA, Wozniak AJ, Belani CP, Keohan ML, Ross HJ, Polikoff JA, et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer. 2005;7:40–6.

    Article  CAS  PubMed  Google Scholar 

  7. Simon GR, Verschraegen CF, Janne PA, Langer CJ, Dowlati A, Gadgeel SM, et al. Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial. J Clin Oncol. 2008;26:3567–72.

    Article  CAS  PubMed  Google Scholar 

  8. Janne PA, Simon GR, Langer CJ, Taub RN, Dowlati A, Fidias P, et al. Phase II trial of pemetrexed and gemcitabine in chemotherapy-naive malignant pleural mesothelioma. J Clin Oncol. 2008;26:1465–71.

    Article  CAS  PubMed  Google Scholar 

  9. Swellengrebel HA, Zoetmulder FA, Smeenk RM, Smeenk RM, Antonini N, Verwaal VJ. Quantitative intra-operative assessment of peritoneal carcinomatosis—a comparison of three prognostic tools. Eur J Surg Oncol. 2009;35:1078–84.

    Article  CAS  PubMed  Google Scholar 

  10. Verwaal VJ, van Tinteren H, van Ruth S, Zoetmulder FA. Predicting the survival of patients with peritoneal carcinomatosis of colorectal origin treated by aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy. Br J Surg. 2004;91:739–46.

    Article  CAS  PubMed  Google Scholar 

  11. Bao P, Bartlett D. Surgical techniques in visceral resection and peritonectomy procedures. Cancer J. 2009;15:204–11.

    Article  PubMed  Google Scholar 

  12. Gusani NJ, Cho SW, Colovos C, Seo S, Franko J, Richard SD, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008;15:754–63.

    Article  PubMed  Google Scholar 

  13. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yan TD, Black D, Savady R, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol. 2007;14:484–92.

    Article  PubMed  Google Scholar 

  15. Austin F, Mavanur A, Sathaiah M, Steel J, Lenzner D, Ramalingam L, et al. Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms. Ann Surg Oncol. 2012;19:1386–93.

    Article  PubMed  Google Scholar 

  16. Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. New Engl J Med. 2006;354:34–43.

    Article  CAS  PubMed  Google Scholar 

  17. Rufian S, Munoz-Casares FC, Briceno J, Díaz CJ, Rubio MJ, Ortega R, et al. Radical surgery-peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol. 2006;94:316–24.

    Article  PubMed  Google Scholar 

  18. Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42.

    Article  PubMed  Google Scholar 

  19. Baratti D, Kusamura S, Cabras AD, Laterza B, Balestra MR, Deraco M. Lymph node metastases in diffuse malignant peritoneal mesothelioma. Ann Surg Oncol. 2010;17:45–53.

    Article  PubMed  Google Scholar 

  20. Schaub NP, Alimchandani M, Quezado M, Kalina P, Eberhardt JS, Hughes MS, et al. A novel nomogram for peritoneal mesothelioma predicts survival. Ann Surg Oncol. 2013;20:555–61.

    Article  PubMed  Google Scholar 

  21. Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366:397–408.

    Article  CAS  PubMed  Google Scholar 

  22. Fennell DA, Gaudino G, O’Byrne KJ, Mutti L, van Meerbeeck J. Advances in the systemic therapy of malignant pleural mesothelioma. Nat Clin Pract Oncol. 2008;5:136–47.

    Article  PubMed  Google Scholar 

  23. Palumbo C, Bei R, Procopio A, Modesti A. Molecular targets and targeted therapies for malignant mesothelioma. Curr Med Chem. 2008;15:855–67.

    Article  CAS  PubMed  Google Scholar 

  24. Bueno R, De Rienzo A, Dong L, Gordon GJ, Hercus CF, Richards WG, et al. Second generation sequencing of the mesothelioma tumor genome. PloS One. 2010;5:e10612.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Melaiu O, Cristaudo A, Melissari E, Di Russo M, Bonotti A, Bruno R, et al. A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma. Mutat Res. 2012;750:132–40.

    Article  CAS  PubMed  Google Scholar 

  26. Lopez-Rios F, Chuai S, Flores R, Shimizu S, Ohno T, Wakahara K, et al. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res. 2006;66:2970–9.

    Article  CAS  PubMed  Google Scholar 

  27. Deraco M, Nonaka D, Baratti D, Casali P, Rosai J, Younan R, et al. Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol. 2006;13:229–37.

    Article  PubMed  Google Scholar 

  28. Feldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, et al. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol. 2003;21:4560–7.

    Article  CAS  PubMed  Google Scholar 

  29. Witkamp AJ, de Bree E, Van Goethem R, Zoetmulder FA. Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev. 2001;27:365–74.

    Article  CAS  PubMed  Google Scholar 

  30. Kusamura S, Dominique E, Baratti D, Younan R, Deraco M. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98:247–52.

    Article  PubMed  Google Scholar 

  31. Yan TD, Haveric N, Carmignani CP, Chang D, Sugarbaker PH. Abdominal computed tomography scans in the selection of patients with malignant peritoneal mesothelioma for comprehensive treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cancer. 2005;103:839–49.

    Article  PubMed  Google Scholar 

  32. Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, et al. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database*. Cancer. 2011;117:1855–63.

    Article  PubMed  Google Scholar 

  33. Low RN, Barone RM. Combined diffusion-weighted and gadolinium-enhanced MRI can accurately predict the peritoneal cancer index preoperatively in patients being considered for cytoreductive surgical procedures. Ann Surg Oncol. 2012;19:1394–401.

    Article  PubMed  Google Scholar 

Download references

Disclosure

None.

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Deepa Magge MD, Frances Austin MD, Arun Mavanur MD, Magesh Sathaiah MD, Lekshmi Ramalingam MD, Heather Jones MPA-C, Amer H. Zureikat MD, Matthew Holtzman MD, Steven Ahrendt MD, James Pingpank MD, Herbert J. Zeh MD, David L. Bartlett MD & Haroon A. Choudry MD

  2. Clinical Research Office for Surgery and Trauma, University of Pittsburgh, Pittsburgh, PA, USA

    Mazen S. Zenati MD, MPH, PhD

Authors
  1. Deepa Magge MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mazen S. Zenati MD, MPH, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frances Austin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arun Mavanur MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Magesh Sathaiah MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lekshmi Ramalingam MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Heather Jones MPA-C
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amer H. Zureikat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Matthew Holtzman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Steven Ahrendt MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. James Pingpank MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Herbert J. Zeh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. David L. Bartlett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Haroon A. Choudry MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to David L. Bartlett MD or Haroon A. Choudry MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magge, D., Zenati, M.S., Austin, F. et al. Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis. Ann Surg Oncol 21, 1159–1165 (2014). https://doi.org/10.1245/s10434-013-3358-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-3358-y

Keywords

Search

Navigation