Annals of Surgical Oncology

, Volume 23, Issue 5, pp 1468–1473 | Cite as

The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

  • Shigeki Kusamura
  • Pilar Adriana Torres Mesa
  • Antonello Cabras
  • Dario Baratti
  • Marcello DeracoEmail author
Gastrointestinal Oncology



We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM).


DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI).


A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively.


Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.


Overall Survival Median Overall Survival Histological Subtype Pemetrexed Cytoreductive Surgery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was partially supported by AIRC (Associazione Italiana per la Ricerca Contro il Cancro).

Conflict of interest

The authors declare that there is no conflict of interest.

Financial support

The present work did not receive any financial support.


  1. 1.
    Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366:397–40.CrossRefPubMedGoogle Scholar
  2. 2.
    Yang H, Testa JR, Carbone M. Mesothelioma epidemiology, carcinogenesis and pathogenesis. Curr Treat Options Oncol. 2008;9:147–157.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Moore AJ, Parker RJ, Wiggins J. Malignant mesothelioma. Orphanet J Rare Dis. 2008;3:34.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Antman KH, Osteen RT, Klegar KL, et al. Early peritoneal mesothelioma: a treatable malignancy. Lancet. 1985;2:977–81.CrossRefPubMedGoogle Scholar
  5. 5.
    Eltabbakh GH, Piver MS, Hempling RE, Recio FO, Intengen ME. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol. 1999;70:6–12.CrossRefPubMedGoogle Scholar
  6. 6.
    Helm JH, Miura JT, Glenn JA, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis. Ann Surg Oncol. 2015;22:1686–93.CrossRefPubMedGoogle Scholar
  7. 7.
    Schaub NP, Alimchandani M, Quezado M, et al. A Novel Nomogram for Peritoneal Mesothelioma Predicts Survival. Ann Surg Oncol. 2013;20:555–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Deraco M, Cabras A, Baratti D, Kusamura S. Immunohistochemical evaluation of minichromosome maintenance protein 7 (MCM7), topoisomerase IIα, and Ki-67 in diffuse malignant peritoneal mesothelioma patients using tissue microarray. Ann Surg Oncol. 2015. doi: 10.1245/s10434-015-4498-z.Google Scholar
  9. 9.
    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;103:839–849.CrossRefPubMedGoogle Scholar
  10. 10.
    Deraco M, Santoro N, Carraro O, et al. Peritoneal carcinomatosis: feature of dissemination. A review. Tumori. 1999;85:1–5.PubMedGoogle Scholar
  11. 11.
    Deraco M, Baratti D, Kusamura S, et al. Surgical technique of parietal and visceral peritonectomy for peritoneal surface malignancies. J Surg Oncol. 2009;100:321–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Rossi CR, Foletto M, Mocellin S, et al. Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study. Cancer. 2002; 94:492–499.CrossRefPubMedGoogle Scholar
  13. 13.
    Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20:1093–100.CrossRefPubMedGoogle Scholar
  14. 14.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40:373–383.CrossRefPubMedGoogle Scholar
  15. 15.
    Mery É, Hommell-Fontaine J, Capovilla M, et al. Peritoneal malignant mesothelioma: review and recent data. Ann Pathol. 2014;34:26–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Younan R, Kusamura S, Baratti D, et al. Morbidity, toxicity, and mortality classification systems in the local regional treatment of peritoneal surface malignancy. J Surg Oncol. 2008;98:253–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Royston P, Sauerbrei W. Building multivariable regression models with continuous covariates in clinical epidemiology—with an emphasis on fractional polynomials. Methods Inf Med. 2005;44:561–71.PubMedGoogle Scholar
  18. 18.
    Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: Issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15:361–87.CrossRefPubMedGoogle Scholar
  19. 19.
    Efron B, Tibshirani RJ. An introduction to the bootstrap. Chapman and Hall, Springer Science, New York, 1993.CrossRefGoogle Scholar
  20. 20.
    Hothorn T ZH. Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat. 2006;15:651–74.CrossRefGoogle Scholar
  21. 21.
    Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer. 2013;49:3140–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Harrell FE Jr. Regression modeling strategies with applications to linear models, logistic regression, and survival analysis. New York, Springer, 2001.Google Scholar
  24. 24.
    Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006; 25:127–141.CrossRefPubMedGoogle Scholar
  25. 25.
    Gouy S, Belghiti J, Uzan C, Canlorbe G, Gauthier T, Morice P. Accuracy and reproducibility of the peritoneal cancer index in advanced ovarian cancer during laparoscopy and laparotomy. Int J Gynecol Cancer. 2013;23:1699–703.CrossRefPubMedGoogle Scholar
  26. 26.
    Nonaka D, Kusamura S, Baratti D, et al. Diffuse malignant mesothelioma of the peritoneum: a clinicopathological study of 35 patients treated locoregionally at a single institution. Cancer. 2005; 104:2181–88.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Shigeki Kusamura
    • 1
  • Pilar Adriana Torres Mesa
    • 1
    • 2
  • Antonello Cabras
    • 3
  • Dario Baratti
    • 1
  • Marcello Deraco
    • 1
    Email author
  1. 1.Peritoneal Surface Malignancy Program, Department of SurgeryFondazione IRCCS Istituto Nazionale Tumori MilanoMilanItaly
  2. 2.European School of Peritoneal Surface Oncology (ESPSO)Centro Nacional de Oncología S.ABogotáColombia
  3. 3.Pathology departmentFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly

Personalised recommendations