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Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer
  1. Jacek P Grabowski1,
  2. Clara Martinez Vila2,
  3. Rolf Richter1,
  4. Eliane Taube3,
  5. Helmut Plett1,4,
  6. Elena Braicu1 and
  7. Jalid Sehouli1
  1. 1 Department of Gynecology with Center of Oncological Surgery, Virchow Campus Clinic, Charite Universitatsmedizin Berlin, Berlin, Germany
  2. 2 Department of Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain
  3. 3 Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany
  4. 4 Department of Gynecology and Gynecologic Oncology, Kliniken-Essen-Mitte, Essen, Germany
  1. Correspondence to Dr Jacek P Grabowski, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin 13353, Germany; jacek.grabowski{at}charite.de

Abstract

Objective Low-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy.

Methods Patients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI).

Results A total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response).

Conclusions This is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

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Footnotes

  • Contributors Guarantor of the integrity of the study: JPG, JS, CMV. Study concepts: JPG, JS. Study design: JPG, JS. Definition of intellectual content: JPG, JS, EB, ET. Literature research: JPG, CMV. Clinical studies: JPG, CMV, ET, EB, HP, JS. Data acquisition: JPG, CMV, RR, EB, ET. Analysis: JPG, CMV, RR, JS. Statistical analysis: JPG, RR, CMV, JS. Manuscript preparation: JPG, CMV, JS. Manuscript editing: JPG, CMV, JS. Manuscript review: JPG, CMV, JS, RR.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available. NA.