Advertisement

International Journal of Clinical Oncology

, Volume 24, Issue 10, pp 1273–1283 | Cite as

Thrombotic events induce the worse prognosis in ovarian carcinomas and frequently develop in ovarian clear cell carcinoma

  • Kazuki Takasaki
  • Morikazu MiyamotoEmail author
  • Masashi Takano
  • Hiroaki Soyama
  • Tadashi Aoyama
  • Hiroko Matsuura
  • Hideki Iwahashi
  • Hiroki Ishibashi
  • Takahiro Sakamoto
  • Kenichi Furuya
Original Article
  • 84 Downloads

Abstract

Background

This study aimed to examine the clinical significance and risk factors of thromboembolic events (TEEs) in patients with ovarian carcinoma.

Methods

Patients with ovarian carcinoma treated at our hospital between 2000 and 2017 were identified. The risk factors of TEEs, including venous TEEs and arterial TEEs, and the association between TEEs and prognosis were investigated. Patients with TEEs were classified into two groups: those with severe TEEs, defined as patients who required urgent treatment for deep vein thrombosis, massive pulmonary embolism, acute myocardial infarction, and symptomatic cerebral infarction, and those with mild TEEs. The risk factors of severe TEEs and the association between severe TEEs and prognosis were investigated.

Results

A total of 369 patients were enrolled. Among them, 53 patients (14.4%) were complicated with TEEs. Clear cell carcinoma (CCC) was a greater risk factor of TEEs than serous carcinoma (hazard ratio [HR] = 2.81, p = 0.03). In multivariate analysis for survival, TEEs were a prognostic factor of poor progression-free survival (PFS; HR = 2.90, p < 0.01) and overall survival (OS; HR = 2.89, p < 0.01). Among 53 patients with TEEs, 17 (32.1%) developed severe TEEs. CCC was strongly associated with severe TEEs (HR = 42.6, p = 0.02). Multivariate analysis for survival demonstrated that severe TEEs were a risk factor of worse PFS (HR = 4.34, p < 0.01) and OS (HR = 3.30, p = 0.03).

Conclusion

TEEs induced poor prognosis and was associated with CCC. A standard treatment for CCC should be included in the strategy of TEEs.

Keywords

Ovarian cancer Thromboembolic events Venous thromboembolism Arterial thromboembolism Clear cell carcinoma 

Notes

Funding

None.

Compliance with ethical standards

Conflicts of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Informed consent

Informed consent was not obtained because our study was a retrospective analysis.

References

  1. 1.
    Baldwin LA, Huang B, Miller RW et al (2012) Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol 120:612–618CrossRefGoogle Scholar
  2. 2.
    Burgers A, Schmalfeldt B (2011) Ovarian cancer diagnosis and treatment. Dtsch Arztebl Int 108:635–641Google Scholar
  3. 3.
    Pujade-Lauraine E, Alexander J (2011) Update of randomized trials in recurrent disease. Ann Oncol Suppl 8:61–64Google Scholar
  4. 4.
    Coleman RL, Monk BJ, Sood AK et al (2013) Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol 10:211–224CrossRefGoogle Scholar
  5. 5.
    Naumann RW, Coleman RL (2011) Management strategies for recurrent platinum-resistant ovarian cancer. Drugs 71:1397–1412CrossRefGoogle Scholar
  6. 6.
    Li M, Li H, Liu F et al (2017) Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy. J Ovarian Res 10:9CrossRefGoogle Scholar
  7. 7.
    Fujiwara K, Shintani D, Nishikawa T (2016) Clear-cell carcinoma of the ovary. Ann Oncol Suppl 1:50–52.  https://doi.org/10.1093/annonc/mdw086 CrossRefGoogle Scholar
  8. 8.
    Miyamoto M, Takano M, Goto T et al (2013) Clear cell histology as a poor prognostic factor for advanced epithelial ovarian cancer: a single institutional case series through central pathologic review. J Gynecol Oncol 24:37–43CrossRefGoogle Scholar
  9. 9.
    Friedlander ML, Russel K, Millis S et al (2016) Molecular profiling of clear cell ovarian cancers: identifying potential treatment targets for clinical trials. Int J Gynecol Cancer 26:648–654CrossRefGoogle Scholar
  10. 10.
    Tan DS, Miller RE, Kaye SB (2013) New perspectives on molecular targeted therapy in ovarian clear cell carcinoma. Br J Cancer 108:1553–1559CrossRefGoogle Scholar
  11. 11.
    Sakurai M, Matsumoto M, Sakata A et al (2017) Expression of tissue factor in epithelial ovarian carcinoma is involved in the development of venous thromboembolism. Int J Gynecol Cancer 27:37–43CrossRefGoogle Scholar
  12. 12.
    Metcalf RL, Fry DJ, Swindell R et al (2014) Thrombosis in ovarian cancer: a case control study. Br J Cancer 110:1118–1124CrossRefGoogle Scholar
  13. 13.
    Cohen JG, Prendergast E, Geddings JE et al (2017) Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer. Gynecol Oncol 146:146–152CrossRefGoogle Scholar
  14. 14.
    Ye S, Yang J, Cao D et al (2015) Characteristic and prognostic implication of venous thromboembolism in ovarian clear cell carcinoma: a 12-year retrospective study. PLoS ONE 10:1–10Google Scholar
  15. 15.
    Kuroda H, Mabuchi S, Shigeta N et al (2014) Recurrent cerebral infarctions in patient with ovarian cancer: a fatal case of Trousseau’s syndrome. Gynecol Obstet 4:1–4CrossRefGoogle Scholar
  16. 16.
    Takano H, Nakajima K, Nagayoshi Y et al (2018) Clinical associations of Trousseau's syndrome associated with cerebral infarction and ovarian cancer. J Gynecol Oncol 29:67CrossRefGoogle Scholar
  17. 17.
    Tateo S, Mereu L, Salamano S et al (2005) Ovarian cancer and venous thromboembolic risk. Gynecol Oncol 99:119–125CrossRefGoogle Scholar
  18. 18.
    Greco PS, Bazzi AA, Mclean K et al (2017) Incidence and timing of thromboembolic events in patients with ovarian cancer undergoing neoadjuvant chemotherapy. Obstet Gynecol 129:979–985CrossRefGoogle Scholar
  19. 19.
    Satoh T, Oki A, Uno K et al (2007) High incidence of silent venous thromboembolism before treatment in ovarian cancer. Br J Cancer 97:1053–1057CrossRefGoogle Scholar
  20. 20.
    Sorensen HT, Mellemkjaer L, Steffensen FH et al (1998) The risk of a diagnosis of cancer after deep vein thrombosis or pulmonary embolism. N Engl J Med 338:1169–1173CrossRefGoogle Scholar
  21. 21.
    Naoi H, Hashimoto H, Kajimoto E et al (2013) Cerebral infarctions as manifestation of ovarian clear cell carcinoma: report of two cases and review of the literature. Int Canc Conf J 2:206–210CrossRefGoogle Scholar
  22. 22.
    Yang CM, Hsieh MY, Lin L et al (2013) Acute myocardial infarction in association with occult ovarian cancer. Acta Cardiol Sin 29:102–106CrossRefGoogle Scholar
  23. 23.
    Prat J, FIGO Committee on Gunecologic Oncology (2015) FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication. J Gynecol Oncol 26:87–89CrossRefGoogle Scholar
  24. 24.
    Ebina Y, Uchiyama M, Imafuki H et al (2018) Risk factors for deep venous thrombosis in women with ovarian cancer. Medicine (Baltimore) 97:1–6CrossRefGoogle Scholar
  25. 25.
    Uno K, Homma S, Satoh T et al (2007) Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 96:290–295CrossRefGoogle Scholar
  26. 26.
    Matsuo K, Hasegawa K, Yoshino K et al (2015) Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma. Eur J Cancer 51:1978–1988CrossRefGoogle Scholar
  27. 27.
    Koizume S, Miyagi Y (2015) Tissue factor-factor VII complex as a key regulator of ovarian cancer phenotypes. Biomarker Cancer 7:1–13Google Scholar
  28. 28.
    Duan Z, Foster R, Bell DA et al (2006) Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 12:5055–5063CrossRefGoogle Scholar
  29. 29.
    Coward J, Kullbe H, Chakravarty P et al (2011) Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res 17:6083–6096CrossRefGoogle Scholar
  30. 30.
    Lane D, Matte I, Rancourt C et al (2011) Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer 11:210CrossRefGoogle Scholar
  31. 31.
    Yoshikawa T, Miyamoto M, Aoyama T et al (2018) JAK2/STAT3 pathway as a therapeutic target in ovarian cancers. Oncol Lett 15:5772–5780Google Scholar
  32. 32.
    Yanaihara N, Hirata Y, Yamaguchi N et al (2015) Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary. Mol Carcinog 55:832–841CrossRefGoogle Scholar
  33. 33.
    Tetsche MS, Nørgaard M, Pedersen L et al (2006) Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study. BMC Cancer 6:189CrossRefGoogle Scholar
  34. 34.
    Einstein MH, Pritts EA, Hartenbach EM (2007) Venous thromboembolism prevention in gynecologic cancer surgery: a systematic review. Gynecol Oncol 105:813–819CrossRefGoogle Scholar
  35. 35.
    Miyamoto M, Takano M, Iwaya K et al (2014) X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary. Br J Cancer 110:2881–2886CrossRefGoogle Scholar
  36. 36.
    Miyamoto M, Takano M, Aoyama T et al (2017) Inhibition of autophagy protein LC3A as a therapeutic target in ovarian clear cell carcinomas. J Gynecol Oncol 28:33CrossRefGoogle Scholar
  37. 37.
    Chavan DM, Huang Z, Song K et al (2017) Incidence of venous thromboembolism following the neoadjuvant chemotherapy regimen for epithelial type of ovarian cancer. Medicine (Baltimore) 96:e7935CrossRefGoogle Scholar
  38. 38.
    Matsuura Y, Robertson G, Marsden DE et al (2007) (2007) Thromboembolic complications in patients with clear cell carcinoma of the ovary. Gynecol Oncol 104:406–410CrossRefGoogle Scholar
  39. 39.
    Kröger K, Weiland D, Ose C et al (2006) Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 17:297–303CrossRefGoogle Scholar
  40. 40.
    De Martino RR, Goodney PP, Spangler EL et al (2012) Variation in thromboembolic complications among patients undergoing commonly performed cancer operations. J Vasc Surg 55:1035–1040CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Kazuki Takasaki
    • 1
  • Morikazu Miyamoto
    • 1
    Email author
  • Masashi Takano
    • 2
  • Hiroaki Soyama
    • 1
  • Tadashi Aoyama
    • 1
  • Hiroko Matsuura
    • 1
  • Hideki Iwahashi
    • 1
  • Hiroki Ishibashi
    • 1
  • Takahiro Sakamoto
    • 1
  • Kenichi Furuya
    • 1
  1. 1.Department of Obstetrics and GynecologyNational Defense Medical College HospitalTokorozawaJapan
  2. 2.Department of Clinical OncologyNational Defense Medical College HospitalTokorozawaJapan

Personalised recommendations