Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer

Abstract

ObjectiveLow-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.MethodsPatients 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).ResultsA 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).ConclusionsThis 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.

Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA

“…Our result indicates no notable differences in the efficacy of curcumin vs. nanocurcumin on the ovarian morphological outcomes. However, nanocurcumin resulted in better outcomes when compared with curcumin in Ki-67 expressions, known prognostic markers, and predictors for chemotherapy outcomes in ovarian cancer ( Mahadevappa et al, 2017 ; Grabowski et al, 2020 ). We believe that a longer duration of treatment with nanocurcumin might result in better overall outcomes and survival in our ovarian cancer model.…”

Low-Grade Serous Carcinoma of the Ovary: The Current Status

“…Ki-67 < 3.6% is associated with substantially longer therapy-free intervals. Additionally, Ki-67 ≥ 4.0% correlates with a superior response rate to chemotherapy [ 67 ]. Therefore, the Ki-67 index is a valuable tool as a prognostic factor, biomarker for therapy outcome, and complete resection predictor in LGSC.…”

Prognostic significance of Ki67 during neoadjuvant chemotherapy in primary unresectable ovarian cancer

“…On the other hand, in low-grade serous ovarian cancer, lower pretherapeutic Ki67 levels are associated with a longer treatment-free interval but a lower chemotherapy response rate. 18,19 This conflicting result may be due to the diametric evidence of lower drug-sensitivity of cancer cells and their indolent progression coming down to protraction of RFS. From such a point of view, monitoring the patients by post-NACT Ki67 and the change in Ki67 score during NACT may be a biologically superior way to predict the therapeutic outcome.…”

“…Numerous studies have reported that high pretherapeutic proliferation index has been shown to correlate with response to chemotherapy and clinical outcome in ovarian cancer patients when they were treated in conventional modality with primary surgery followed by chemotherapy, 16,17 while our NACT study showed no significant association between pre‐NACT Ki67 level and survival. On the other hand, in low‐grade serous ovarian cancer, lower pretherapeutic Ki67 levels are associated with a longer treatment‐free interval but a lower chemotherapy response rate 18,19 . This conflicting result may be due to the diametric evidence of lower drug‐sensitivity of cancer cells and their indolent progression coming down to protraction of RFS.…”