ObjectiveOvarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival.MethodsPredictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment.ResultsIn a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36–1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05–0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40–1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42–1.40, P = 0.386).ConclusionIn the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance to adjuvant chemotherapy, PFS, and overall survival were analyzed in univariate analyses and in multivariate analyses adjusted for age, performance score, surgical outcome, stage, grade, and histological subtype. Serum HE4 levels predicted chemotherapy resistance, PFS, and overall survival correlated significantly (p < 0.001) in the univariate analyses; but after adjustment in a multivariate model, serum HE4 was insignificant, except in a subgroup analysis of postmenopausal women, where serum HE4 significantly predicted resistance to chemotherapy and progression-free survival. HE4 tissue protein expression predicted PFS (p = 0.022) and overall survival (p = 0.047) in the univariate analysis, while HE4 tissue protein expression failed to predict these outcomes in the adjusted multivariate analyses. Serum HE4 or HE4 tissue protein expression are not independent factors of chemotherapy resistance or survival in patients with EOC, but serum HE4 might predict chemotherapy resistance and PFS in postmenopausal women.

decreased among women <70 years of age but was stable for women ≥70 years during 2005-2018.• The proportion of patients with advanced EOC not undergoing debulking surgery increased from 2005 to 2018.• During the same period, the proportion of patients having 0 cm residual disease after debulking surgery increased.• During the same period, cancer-specific survival increased for both younger and older EOC patients.

Background/Aim: The aim of the study was to compare platinum resistance and treatment-free interval (TFI) following treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS) in women with advanced epithelial ovarian cancer (EOC). Patients and Methods: The study included patients diagnosed with primary EOC, stage IIIC or IV, between 2005 and. Patients were grouped according to first-line treatment (PDS vs. NACT-IDS). Date of second-line treatment initiation was used to evaluate platinum sensitivity. Results: The study population included 521 patients, of which 371 (71%) and 150 (29%) underwent PDS and NACT-IDS, respectively. We found no difference in platinum resistance between groups. Platinum-sensitive patients treated with NACT-IDS had a shorter median TFI (372 vs. 497 days, p=0.042). Similarly, patients with no residual tumor after IDS had a shorter median TFI (280 vs. 302 days, p=0.005). Conclusion: NACT-IDS may shorten the TFI after first-line platinum-based chemotherapy.Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies (1, 2). Most women are diagnosed in advanced stages (The International Federation of Gynecology and Obstetrics (FIGO) stage III-IV), for which the prognosis is poor (3). The traditional treatment for EOC is primary debulking surgery (PDS) followed by adjuvant platinum-based chemotherapy (4). However, in the last decade, the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has increased (5, 6).For PDS, complete tumor resection has a profoundly positive impact on survival (7, 8). However, while randomized controlled trials comparing PDS to NACT-IDS demonstrated superior surgical outcomes for NACT-IDS, this finding did not translate into better survival (9, 10). Another important factor regarding survival is platinum sensitivity to first-line chemotherapy since platinumresistant disease is associated with poor prognosis (4,(11)(12)(13). The potential risk of developing platinum resistance rises with increasing tumor burden (14). Accordingly, patients treated with chemotherapy before debulking surgery may be more susceptible to developing resistance to chemotherapy.Hypothetically, the reason why the superior surgical outcomes of NACT-IDS do not translate into better survival could in part be explained by a greater likelihood of developing platinum resistance when treated with NACT-IDS than when treated with PDS. Thus, the present study compared platinum resistance and treatment-free interval (TFI) after first-line treatment with PDS or NACT-IDS. Patients and MethodsStudy population. This study included patients treated at Copenhagen University Hospitals, Rigshospitalet or Herlev Hospital, and identified in the Danish Gynecological Cancer Database (DGCD) (15) between January 2005 and May 2013 with primary epithelial stage IIIC or IV cancer in the ovaries, fallopian tubes, or peritoneum. We selected two university hospitals from the greater Copenhagen region...

BACKGROUND:This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced highgrade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. Cancer 2022;128:3080-3089.

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