Skip to main content

Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series

Abstract

Purpose

Cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy is standard of care for diffuse malignant peritoneal mesothelioma (DMPM), but there is variability among institutions in the administration of adjuvant chemotherapy. Characterization of the largest series of DMPM patients treated at a single institution and identification of the demographic, disease, and treatment factors associated with overall survival were sought.

Patients and Methods

All DMPM patients who underwent initial cytoreductive surgery with the intention to undergo intraperitoneal chemotherapy and a second-look operation from 1995 to 2016 at our institution were retrospectively reviewed. The primary endpoint was overall survival.

Results

A total of 204 DMPM patients underwent initial cytoreduction. Median overall survival was 32 months from initial cytoreduction. Independent baseline prognostic factors of improved overall survival were female sex, age < 60 years, and epithelioid histology. Independent treatment factors associated with improved overall survival were attempted resection at initial operation, residual disease < 0.5 cm at the end of the initial operation, and dwell intraperitoneal chemotherapy.

Conclusions

Cytoreductive surgery with intraoperative and dwell intraperitoneal chemotherapy is a feasible approach for DMPM. Expanded access to these therapies may offer benefit to a larger population of patients. Demographic and operative parameters associated with overall survival in this large cohort are consistent with previous reports. In the context of this treatment protocol, dwell intraperitoneal chemotherapy is associated with longer overall survival.

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

Fig. 1
Fig. 2

References

  1. Turaga KK, Deraco M, Alexander HR. Current management strategies for peritoneal mesothelioma. Int J Hyperthermia. 2017;33(5):579–81.

    Article  Google Scholar 

  2. Sugarbaker PH. Five Reasons why cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy must be regarded as the new standard of care for diffuse malignant peritoneal mesothelioma. Ann Surg Oncol. 2010;17(6):1710–2.

    Article  Google Scholar 

  3. Turner KM, Varghese S, Alexander HR Jr. Surgery for peritoneal mesothelioma. Curr Treat Opt Oncol. 2011;12(2):189–200.

    Article  Google Scholar 

  4. Leinwand JC, Chabot JA, Kluger MD. Preventing recurrence of diffuse malignant peritoneal mesothelioma. Expert Rev Anticancer Ther. 2016;16(9):989–95.

    CAS  Article  Google Scholar 

  5. Deraco M, Bartlett D, Kusamura S, Baratti D. Consensus statement on peritoneal mesothelioma. J Surg Oncol. 2008;98(4):268–72.

    Article  Google Scholar 

  6. 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(5):827–34.

    CAS  Article  Google Scholar 

  7. Saxena A, Chua TC. Results of systemic pemetrexed-based combination chemotherapy versus cytoreductive surgery and hyperthermic intraperitoneal cisplatin and doxorubicin on survival in malignant peritoneal mesothelioma. Lung Cancer. 2009;66(2):269–70.

    Article  Google Scholar 

  8. Alexander HR Jr, Bartlett DL, Pingpank JF, Libutti SK, Royal R, Hughes MS, Holtzman M, Hanna N, Turner K, Beresneva T, Zhu Y. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery. 2013;153:779–86.

    Article  Google Scholar 

  9. Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, Gilly FN, Levine EA, Shen P, Mohamed F, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.

    Article  Google Scholar 

  10. Kluger MD, Taub RN, Hesdorffer M, Jin Z, Chabot JA. Two-stage operative cytoreduction and intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma: Operative morbidity and mortality in phase I and II trials. Eur J Surg Oncol. 2010;36(10):997–1003.

    CAS  Article  Google Scholar 

  11. Garcia-Carbonero R, Paz-Ares L. Systemic chemotherapy in the management of malignant peritoneal mesothelioma. Eur J Surg Oncol. 2006;32(6):676–81.

    CAS  Article  Google Scholar 

  12. Jänne PA, Wozniak AJ, Belani CP, Keohan ML, Ross HJ, Polikoff JA, Mintzer DM, Taylor L, Ashland J, Ye Z, Monberg MJ, Obasaju CK. 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(1):40–6.

    Article  Google Scholar 

  13. Schutte W, Blankenburg T, Lauerwald K, Schreiber J, Bork I, Wollscgkaeger B, Treutler D, Schneider CP, Bonner R. A multicenter phase II study of gemcitabine and oxaliplatin for malignant pleural mesothelioma. Clin Lung Cancer. 2003;4(5):294–7.

    Article  Google Scholar 

  14. Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, Liu Y, Blatter J, Visseren-Grul C, Stahel R. Malignant peritoneal mesothelioma—results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent. Lung Cancer. 2009;64(2):211–8.

    CAS  Article  Google Scholar 

  15. Reck M, Stahel RA, von Pawel J, Karthaus M, Korfee S, Serke M, Schuette WH, Eschbach C, Fink TH, Leschinger MI, Manegold C. Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. Respir Med. 2010;104(1):142–8.

    Article  Google Scholar 

  16. Markman M. Continued uncertainty regarding hyperthermic intraperitoneal chemotherapy in malignant peritoneal mesothelioma. J Clin Oncol. 2010;28(24):e418.

    Article  Google Scholar 

  17. Markman M. Current status of intraperitoneal antineoplastic drug delivery. Cancer Treat Res. 2007;134:153–69.

    CAS  PubMed  Google Scholar 

  18. Bartlett DL. HIPEC: the complexities of clinical trials. Ann Surg Oncol. 2008;15(5):1277–9.

    Article  Google Scholar 

  19. Hesdorffer ME, Chabot JA, Keohan ML, Fountain K, Talbot S, Gabay M, Valentin C, Lee SM, Taub RN. Combined resection, intraperitoneal chemotherapy, and whole abdominal radiation for the treatment of malignant peritoneal mesothelioma. Am J Clin Oncol. 2008;31(1):49–54.

    CAS  Article  Google Scholar 

  20. Malignant mesothelioma: Number of deaths by sex, race, age group, and median age at death, U.S. residents age 15 and over, 2005–2014. Mortality multiple cause-of-death data from National Center for Health Statistics, National Vital Statistics System. https://wwwn.cdc.gov/eworld/Data/897. Accessed 29 Aug 2019.

  21. Kim J, Bhagwandin S, Labow DM. Malignant peritoneal mesothelioma: a review. Ann Transl Med. 201;5(11):236.

    Article  Google Scholar 

  22. Yan TD, Edwards G, Alderman R, Marquardt CE, Sugarbaker PH. Morbidity and mortality assessment of cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma—a prospective study of 70 consecutive cases. Ann Surg Oncol. 2007;14(2):515–25.

    Article  Google Scholar 

  23. Cao C, Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH; Peritoneal Surface Malignancy Group. Importance of gender in diffuse malignant peritoneal mesothelioma. Ann Oncol. 2012;23(6):1494–8.

  24. Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH; Peritoneal Surface Oncology Group. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database*. Cancer. 2011;117(9):1855–63.

  25. Shavelle R, Vavra-Musser K, Lee J, Brooks J. Life expectancy in pleural and peritoneal mesothelioma. Lung Cancer Int. 2017;2017:2782590.

    Article  Google Scholar 

  26. Feldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, Steinberg SM, Liewehr DJ, Kleiner DE, Alexander HR. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol. 2003;21(24):4560–7.

    CAS  Article  Google Scholar 

  27. Flores RM, Zakowski M, Venkatraman E, et al. Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center. J Thorac Oncol. 2007;2(10):957–65.

    Article  Google Scholar 

  28. Saddoughi SA, Abdelsattar ZM, Blackmon SH. National trends in the epidemiology of malignant pleural mesothelioma: a national cancer data base study. Ann Thorac Surg. 2018;105(2):432–7.

    Article  Google Scholar 

  29. Letica-Kriegel AS, Leinwand JC, Sonett JR, Gorenstein LA, Taub RN, Chabot JA, Kluger MD. 50 Patients with malignant mesothelioma of both the pleura and peritoneum: a single-institution experience. Ann Surg Oncol. 2019.

  30. Heller DR, Chiuzan C, Taub RN, Leinwand JC, Greene AM, Bates GE, Chabot JA, Kluger MD. Recurrence of optimally treated malignant peritoneal mesothelioma with cytoreduction and heated intraperitoneal chemotherapy. Ann Surg Oncol. 2017;24(13):3818–24.

    Article  Google Scholar 

  31. Baratti D, Kusamura S, Cabras AD, Dileo P, Laterza B, Deraco M. Diffuse malignant peritoneal mesothelioma: failure analysis following cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol. 2009;16:463–72.

    CAS  Article  Google Scholar 

  32. Huang Y, Alzahrani NA, Liauw W, Morris DL. Repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent diffuse malignant peritoneal mesothelioma. Eur J Surg Oncol. 2015;41(10):1373–78.

    CAS  Article  Google Scholar 

  33. Wong J, Koch AL, Deneve JL, Fulp W, Tanvetyanon T, Dessureault S. Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience. Ann Surg Oncol. 2014;21(5):1480–86.

    Article  Google Scholar 

  34. Ihemelandu C, Bijelic L, Sugarbaker PH. Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome. Ann Surg Oncol. 2015;22(5):1680–85.

    Article  Google Scholar 

  35. Leinwand JC, Bates GE, Allendorf JD, Chabot JA, Lewin SN, Taub RN. Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(4):1101–4.

    Article  Google Scholar 

  36. Shetty SJ, Bathla L, Govindarajan V, Thomas P, Loggie BW. Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma. Am Surg. 2014;80(4):348–52.

    PubMed  Google Scholar 

  37. Helm JH, Miura JT, Glenn JA, Marcus RK, Larrieux G, Jayakrishnan TT, Donahue AE, Gamblin TC, Turaga KK, Johnston FM. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis. Ann Surg Oncol. 2015;22(5):1686–93.

    Article  Google Scholar 

  38. Sugarbaker PH, Chang D. Long-term regional chemotherapy for patients with epithelial malignant peritoneal mesothelioma results in improved survival. Eur J Surg Oncol. 2017;43(7):1228–35.

    CAS  Article  Google Scholar 

  39. Leinwand JC, Zhao B, Guo X, Krishnamoorthy S, Qi J, Graziano JH, Slavkovic VN, Bates GE, Lewin SN, Allendorf JD, Chabot JA, Schwartz LH, Taub RN. Quantitative X-ray computed tomography peritoneography in malignant peritoneal mesothelioma patients receiving intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(Suppl 3):S553–9.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael D. Kluger MD, MPH.

Ethics declarations

Disclosures

None.

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 18 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Leinwand, J.C., Taub, R.N., Chabot, J.A. et al. Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series. Ann Surg Oncol 27, 2539–2547 (2020). https://doi.org/10.1245/s10434-019-08139-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-08139-4