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The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc–IV high-grade serous ovarian cancer

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Abstract

Objective

No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc–IV high-grade serous ovarian cancer (HG-SOC).

Materials and Methods

A total of 129 IIIc–IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test.

Results

The median number of NAC cycle was 3 (range 1–8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months).

Conclusion

NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

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Fig. 1
Fig. 2

Abbreviations

IDS:

Interval cytoreduction surgery

PDS:

Primary debulking surgery

NAC:

Neoadjuvant chemotherapy

OS:

Overall survival

PFS:

Progression free survival

EOC:

Epithelial ovarian cancer

References

  1. Siegel RL et al (2015) Cancer statistics for Hispanics/Latinos, 2015. CA Cancer J Clin 65(6):457–480

    Article  PubMed  Google Scholar 

  2. Jung KW et al (2015) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2012. Cancer Res Treat 47(2):127–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chen W (2015) Cancer statistics: updated cancer burden in China. Chin J Cancer Res 27(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  4. Torre LA et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108

    Article  PubMed  Google Scholar 

  5. Bast RC Jr, Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 9(6):415–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen W et al (2015) Annual report on status of cancer in China, 2011. Chin J Cancer Res 27(1):2–12

    Article  PubMed  PubMed Central  Google Scholar 

  7. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29

    Article  PubMed  Google Scholar 

  8. Hoskins WJ et al (1994) The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 170(4):974–979 (discussion 979–980)

  9. Bristow RE et al (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20(5):1248–1259

    Article  PubMed  Google Scholar 

  10. Elattar A et al (2011) Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 8:CD007565

  11. Vergote I, Amant F, Leunen K (2010) Neoadjuvant chemotherapy in advanced ovarian cancer: what kind of evidence is needed to convince US gynaecological oncologists? Gynecol Oncol 119(1):1–2

    Article  PubMed  Google Scholar 

  12. Chi DS et al (2006) What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol 103(2):559–564

    Article  CAS  PubMed  Google Scholar 

  13. Vergote I et al (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363(10):943–953

    Article  CAS  PubMed  Google Scholar 

  14. Bian C et al (2016) Primary debulking surgery vs. neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer. Arch Gynecol Obstet 293(1):1–6

    Article  Google Scholar 

  15. Petrillo M et al (2014) Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer. Am J Obstet Gynecol 211(6):632 e1–e8

  16. da Costa Miranda V et al (2014) Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: safety and effectiveness. Gynecol Oncol 132(2):287–291

    Article  PubMed  Google Scholar 

  17. Giannopoulos T et al (2006) Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Eur J Gynaecol Oncol 27(1):25–28

    CAS  PubMed  Google Scholar 

  18. Lee SJ et al (2006) Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. J Obstet Gynaecol Res 32(1):99–106

    Article  CAS  PubMed  Google Scholar 

  19. Bilici A et al (2010) Neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients with unresectable, advanced stage epithelial ovarian cancer: a single centre experience. Arch Gynecol Obstet 282(4):417–425

    Article  CAS  PubMed  Google Scholar 

  20. Wright AA et al (2016) Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: society of gynecologic oncology and american society of clinical oncology clinical practice guideline. J Clin Oncol 34(28):3460–3473

    Article  PubMed  Google Scholar 

  21. Bristow RE, Chi DS (2006) Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol 103(3):1070–1076

    Article  CAS  PubMed  Google Scholar 

  22. Onda T, Yoshikawa H (2011) Neoadjuvant chemotherapy for advanced ovarian cancer: overview of outcomes and unanswered questions. Expert Rev Anticancer Ther 11(7):1053–1067

    Article  PubMed  Google Scholar 

  23. Taşkın S et al (2013) Neoadjuvant chemotherapy equalizes the optimal cytoreduction rate to primary surgery without improving survival in advanced ovarian cancer. Arch Gynecol Obstet 288(6):1399–1403

    Article  PubMed  Google Scholar 

  24. Vasudev NS et al (2011) The prognostic and predictive value of CA-125 regression during neoadjuvant chemotherapy for advanced ovarian or primary peritoneal carcinoma. Arch Gynecol Obstet 284(1):221–227

    Article  CAS  PubMed  Google Scholar 

  25. Angioli R et al (2013) Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecol Oncol 128(3):579–583

    Article  CAS  PubMed  Google Scholar 

  26. Seifert H et al (2015) Poor performance status (PS) is an indication for an aggressive approach to neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer (EOC). Gynecol Oncol 139(2):216–220

    Article  PubMed  Google Scholar 

  27. Vallius T et al (2015) 18 F-FDG-PET/CT can identify histopathological non-responders to platinum-based neoadjuvant chemotherapy in advanced epithelial ovarian cancer. Gynecol Oncol 140(1):29–35

    Article  PubMed  Google Scholar 

  28. Pölcher M et al (2010) Changes in Ki-67 labeling indices during neoadjuvant chemotherapy for advanced ovarian cancer are associated with survival. Int J Gynecol Cancer 20(4):555–560

    Article  PubMed  Google Scholar 

  29. Pölcher M et al (2010) Foxp3+ cell infiltration and granzyme B+/Foxp3+ cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother 59(6):909–919

    Article  PubMed  Google Scholar 

  30. Samar MM et al (2015) Vascular endothelial growth factor expression correlates with serum CA125 and represents a useful tool in prediction of refractoriness to platinum-based chemotherapy and ascites formation in epithelial ovarian cancer. Oncotarget 6(29):28491–28501

    Article  Google Scholar 

  31. Xu X et al (2013) Secondary cytoreduction surgery improves prognosis in platinum-sensitive recurrent ovarian cancer. J Exp Clin Cancer Res 32:61

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chen X et al (2013) Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma. Hum Pathol 44(11):2373–2384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen X et al (2013) CA-125 level as a prognostic indicator in type I and type II epithelial ovarian cancer. Int J Gynecol Cancer 23(5):815–822

    Article  PubMed  PubMed Central  Google Scholar 

  34. Xu X et al (2013) Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer. J Ovarian Res 6:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang F et al (2013) CA-125-indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery. J Ovarian Res 6(1):14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Therasse P et al (2000) 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 92(3):205–216

    Article  CAS  PubMed  Google Scholar 

  37. Dai-yuan M et al (2013) A meta-analysis: neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma FIGO stageIII and IV. World J Surg Oncol 11:267

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kehoe S et al (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 386(9990):249–257

    Article  PubMed  Google Scholar 

  39. Fagotti A et al (2016) Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer 59:22–33

    Article  PubMed  Google Scholar 

  40. Onda T et al (2016) Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. Eur J Cancer 64:22–31

    Article  PubMed  Google Scholar 

  41. Kang S (2015) Neoadjuvant chemotherapy for ovarian cancer: do we have enough evidence? Lancet 386(9990):223–224

    Article  PubMed  Google Scholar 

  42. van Meurs HS et al (2013) Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Eur J Cancer 49(15):3191–3201

    Article  PubMed  Google Scholar 

  43. Cornelis S et al (2012) Role of neoadjuvant chemotherapy in the management of stage IIIC–IV ovarian cancer: survey results from the members of the European Society of Gynecological Oncology. Int J Gynecol Cancer 22(3):407–416

    Article  PubMed  Google Scholar 

  44. Vergote I et al (2011) Neoadjuvant chemotherapy is the better treatment option in some patients with stage IIIc to IV ovarian cancer. J Clin Oncol 29(31):4076–4078

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Chemotherapy, Jiangsu Cancer Hospital, 42# Baiziting Street, Nanjing, 210009, Jiangsu, People’s Republic of China

    Xia Xu

  2. Department of Gynecologic Oncology, Jiangsu Cancer Hospital, 42# Baiziting Street, Nanjing, 210009, Jiangsu, People’s Republic of China

    Fei Deng, Mengmeng Lv & Xiaoxiang Chen

Authors
  1. Xia Xu
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  2. Fei Deng
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  3. Mengmeng Lv
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  4. Xiaoxiang Chen
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Corresponding author

Correspondence to Xiaoxiang Chen.

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Ethics approval and consent to participate

This retrospective study was approved by the institutional review board of Jiangsu Cancer Hospital, Nanjing Medical University, China. The informed consent requirement was waived. The committee’s reference number was Jiangsu Cancer Hospital’s Ethical Committee 2016-219.

Conflict of interest

The authors declare that they have no competing interests.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81472441), Natural Science Foundation of Jiangsu Province, China (No. BK20131439), and six major talent summit (No. 2013-wsn-62).

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Xu, X., Deng, F., Lv, M. et al. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc–IV high-grade serous ovarian cancer. Arch Gynecol Obstet 295, 451–458 (2017). https://doi.org/10.1007/s00404-016-4256-x

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