Advertisement

Annals of Surgical Oncology

, Volume 14, Issue 2, pp 500–508 | Cite as

Circulating CA125 in Patients with Peritoneal Mesothelioma Treated with Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

  • Dario Baratti
  • Shigeki Kusamura
  • Antonia Martinetti
  • Ettore Seregni
  • Daniela G. Oliva
  • Barbara Laterza
  • Marcello DeracoEmail author
Article

Abstract

Background

Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP.

Methods

Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules ≤ 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined.

Results

Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy.

Conclusions

CA125 was elevated in the majority of patients with PM in the present series. Serial maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.

Keywords

CA125 Peritoneal mesothelioma Peritonectomy Intraperitoneal hyperthermic perfusion Serum tumor markers Loco-regional chemotherapy 

Notes

Acknowledgments

The authors are indebted to Cristiana Carniti, MD, PhD for assistance in writing the manuscript.

References

  1. 1.
    Antman K, Shemin R, Ryan L, et al. Malignant mesothelioma: prognostic variables in a registry of 180 patients. The Dana-Farber Cancer Institute and Brigham and Women’s Hospital experience over two decades, 1965–1985. JCO 1988; 6:147–153Google Scholar
  2. 2.
    Antman KH, Blum RH, Greenberger JS, et al. Multimodality therapy for malignant mesothelioma based on a study of natural history. Am J Med 1980; 68:356–362PubMedCrossRefGoogle Scholar
  3. 3.
    Eltabbakh GH, Piver MS, Hempling RE. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol 1999; 70:6–12PubMedCrossRefGoogle Scholar
  4. 4.
    Sugarbaker PH. Peritonectomy procedures. Surg Oncol Clin North Am 2003; 12:703–727CrossRefGoogle Scholar
  5. 5.
    Stewart JH, Perry S, Levine EA. Intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy:current status and future directions. Ann Surg Oncol 2005; 12:765–777PubMedCrossRefGoogle Scholar
  6. 6.
    Deraco M, Casali P, Inglese MG, et al. Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. J Surg Oncol 2003; 83:147–53PubMedCrossRefGoogle Scholar
  7. 7.
    Park BJ, Alexander HR, Libutti SK, et al. Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP). Ann Surg Oncol 1999; 6:582–590PubMedCrossRefGoogle Scholar
  8. 8.
    Sebbag G, Yan H, Shmookler BM, et al. Results of treatment of 33 patients with peritoneal mesothelioma. Br J Surg 2000; 87:1587–1593PubMedCrossRefGoogle Scholar
  9. 9.
    Loggie BW, Fleming RA, McQuellon RP, et al. Prospective trial for the treatment of malignant peritoneal mesothelioma. Am Surg 2001; 67:999–1003PubMedGoogle Scholar
  10. 10.
    Sugarbaker PH, Welch LS, Mohamed F, et al. A review of peritoneal mesothelioma at the Washington Cancer Institute. Surg Oncol Clin North Am 2003; 12:605–621CrossRefGoogle Scholar
  11. 11.
    Feldman AL, Libutti SK, Pingpank JF, et al. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol 2003; 21:4560–4567PubMedCrossRefGoogle Scholar
  12. 12.
    Nonaka D, Kusamura S, Baratti D, et al. Diffuse malignant mesothelioma of the peritoneum. Cancer 2005; 104:2181–2188PubMedCrossRefGoogle Scholar
  13. 13.
    Brigand C, Monneuse O, Mohamed F, et al. Peritoneal mesothelioma treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy: results of a prospective study. Ann Surg Oncol 2006; 13:405–412PubMedCrossRefGoogle Scholar
  14. 14.
    Bagshawe KD, Rustin GJ. (1995) Circulating tumour markers. In: Peckham M, Pinedo H, Veronesi U, eds. Oxford Textbook of Oncology. Oxford University Press, Oxford, UK, pp 412–420Google Scholar
  15. 15.
    Weiss SW. World Health Organization Istological Classification of tomors. Histological typing of soft tissue tumours. 2nd edition. Berlin: Springer-Verlag, 1994Google Scholar
  16. 16.
    Oken MM, Creech RH, Tormey, et al. Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:649–655Google Scholar
  17. 17.
    Esquivel JE, Sugarbaker PH. Elective surgery in recurrent colon cancer with peritoneal seeding: when to and when not to. Cancer Ther 1998; 1:321–325Google Scholar
  18. 18.
    Jaquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 1996; 15:49–58Google Scholar
  19. 19.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92:205–216PubMedCrossRefGoogle Scholar
  20. 20.
    Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Soc 1958; 53:457–481Google Scholar
  21. 21.
    Cox DR. Regression models and life tables (with discussion). J R Stat Soc B 1972; 34:187–220Google Scholar
  22. 22.
    Hayes AJ, Mostyn-Jones A, Koban MU, et al. Serum vascolar growth factor as a tumor marker in soft tissue sarcoma. Br J Surg 2004; 91:242–247PubMedCrossRefGoogle Scholar
  23. 23.
    Robinson BW, Creaney J, Lake R, et al. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 2003; 362:1612–1616PubMedCrossRefGoogle Scholar
  24. 24.
    Pass HI, Lott D, Lonardo F, et al. Asbestos exposure, pleural mesothelioma and serum osteopontin level. N Engl J Med 2005; 353:1564–1573PubMedCrossRefGoogle Scholar
  25. 25.
    Hedman M, Arnberg H, Wernlund J, et al. Tissue polypeptide antigen (TPA), hyaluronian and CA125 as serum markers in malignant mesothelioma. Anticancer Res 2003, 23:531–536PubMedGoogle Scholar
  26. 26.
    Simsek H, Kadayifci A, Okan E. Importance of serum CA125 levels in malignant peritoneal mesothelioma. Tumour Biol 1996; 17:1–4PubMedCrossRefGoogle Scholar
  27. 27.
    Bast RC, Feeney M, Lazarus H, et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981; 68:1331–1337PubMedCrossRefGoogle Scholar
  28. 28.
    Rustin GJS, Timmers P, Nelstrop P, Shreeves G, Bentzen SM, Baron B, et al. Comparison of CA-125 and Standard Definitions of Progression of Ovarian Cancer in the Intergroup Trial of Cisplatin and Paclitaxel Versus Cisplatin and Cyclophosphamide Journal of Clinical Oncology 2006; 24:45–51PubMedCrossRefGoogle Scholar
  29. 29.
    Kerin MJ, McAnena OJ, O’Malley VP, et al. CA15–3: its relationship to clinical stage and progression to metastatic disease in breast cancer. Br J Surg 1989; 76:838–839PubMedCrossRefGoogle Scholar
  30. 30.
    Ordonez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol 1998; 22:1203–1214PubMedCrossRefGoogle Scholar
  31. 31.
    Bateman AC, al-Talib RK, Newman Y, et al. Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression. Histopathology 1997; 30:49–56PubMedCrossRefGoogle Scholar
  32. 32.
    Duan HJ, Itoh N, Yamagami O, et al. Diffuse malignant peritoneal mesothelioma in a young woman with a high serum level of CA125. Acta Pathol Jpn 1991; 41:158–163PubMedGoogle Scholar
  33. 33.
    Almudevar Bercero E, Garcia-Rostan Perez GM, Garcia Bragado F, et al. Prognostic value of high serum levels of CA-125 in malignant secretory peritoneal mesotheliomas affecting young women. A case report with differential diagnosis and review of the literature. Histopathology 1997; 31:267–273PubMedCrossRefGoogle Scholar
  34. 34.
    Kebapci M, Vardareli E, Adapinar B, et al. CT findings and serum CA125 levels in malignant peritoneal mesothelioma: report of 11 new cases and review of the literature. Eur Radiol 2003; 13:2620–2626PubMedCrossRefGoogle Scholar
  35. 35.
    Begent R, Rustin GJ. Tumour markers: from carcinoembryonic antigen to products of hybridoma technology. Cancer Surv 1989; 8:107–21PubMedGoogle Scholar
  36. 36.
    Van Ruth S, Hart AA, Bonfrer JM, et al. Prognostic value of baseline and serial carcinoembryonic antigen and carbohydrate antigen 19.9 measurements in patients with pseudomyxoma peritonei treated with cytoreduction and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 2002; 9:961–967PubMedCrossRefGoogle Scholar
  37. 37.
    Garcia-Carbonero R, Paz-Arez L. Systemic chemotherapy in the management of malignant peritoneal mesothelioma. Eur J Surg Oncol 2006; 32:676–681PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Dario Baratti
    • 1
  • Shigeki Kusamura
    • 1
  • Antonia Martinetti
    • 2
  • Ettore Seregni
    • 2
  • Daniela G. Oliva
    • 1
    • 3
  • Barbara Laterza
    • 1
  • Marcello Deraco
    • 1
    Email author
  1. 1.Department of SurgeryNational Cancer InstituteMilanItaly
  2. 2.Department of Nuclear MedicineNational Cancer InstituteMilanItaly
  3. 3.Department of SurgeryUniversity of MessinaMessinaItaly

Personalised recommendations