scholarly journals The Uncertain Benefit of Adjuvant Chemotherapy in Advanced Low-Grade Serous Ovarian Cancer and the Pivotal Role of Surgical Cytoreduction

2021 ◽  
Vol 10 (24) ◽  
pp. 5927
Author(s):  
Racheal Louise Johnson ◽  
Alexandros Laios ◽  
David Jackson ◽  
David Nugent ◽  
Nicolas Michel Orsi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Complete Cytoreduction ◽  
Low Grade ◽  
Serous Ovarian Cancer ◽  
Prognostic Features ◽  
Significant Survival ◽  
Surgical Complexity

In our center, adjuvant chemotherapy is routinely offered in high-grade serous ovarian cancer (HGSOC) patients but less commonly as a standard treatment in low-grade serous ovarian cancer (LGSOC) patients. This study evaluates the efficacy of this paradigm by analysing survival outcomes and by comparing the influence of different clinical and surgical characteristics between women with advanced LGSOC (n = 37) and advanced HGSOC (n = 300). Multivariate analysis was used to identify independent prognostic features for survival in LGSOC and HGSOC. Adjuvant chemotherapy was given in 99.7% of HGSOC patients versus in 27% of LGSOC (p < 0.0001). The LGSOC patients had greater surgical complexity scores (p < 0.0001), more frequent postoperative ICU/HDU admissions (p = 0.0002), and higher peri-/post-operative morbidity (p < 0.0001) compared to the HGSOC patients. The 5-year OS and progression-free survival (PFS) was 30% and 13% for HGSOC versus 57% and 21.6% for LGSOC, p = 0.016 and p = 0.044, respectively. Surgical complexity (HR 5.3, 95%CI 1.2–22.8, p = 0.024) and complete cytoreduction (HR 62.4, 95% CI 6.8–567.9, p < 0.001) were independent prognostic features for OS in LGSOC. This study demonstrates no clear significant survival advantage of chemotherapy in LGSOC. It highlights the substantial survival benefit of dynamic multi-visceral surgery to achieve complete cytoreduction as the primary treatment for LGSOC patients.

Adjuvant chemotherapy beneficial for select early-stage, low-grade serous ovarian cancer patients

2016 ◽  
Vol 141 ◽  
pp. 187-188
Author(s):  
S. Grabosch ◽  
J. Berger ◽  
S.E. Taylor ◽  
J.F. Lin ◽  
M. Courtney-Brooks ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Low Grade ◽  
Serous Ovarian Cancer

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

2020 ◽  
Vol 30 (4) ◽  
pp. 498-503 ◽  
Author(s):  
Jacek P Grabowski ◽  
Clara Martinez Vila ◽  
Rolf Richter ◽  
Eliane Taube ◽  
Helmut Plett ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Serous Ovarian Cancer ◽  
Ki67 Expression ◽  
Residual Mass ◽  
Ovarian Cancers ◽  
Free Interval ◽  
Neo Adjuvant Chemotherapy

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.

scholarly journals Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3727
Author(s):  
Dafne Jacome Sanz ◽  
Juuli Raivola ◽  
Hanna Karvonen ◽  
Mariliina Arjama ◽  
Harlan Barker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lipid Metabolism ◽  
Cell Survival ◽  
Drug Testing ◽  
Cancer Metabolism ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Low Grade ◽  
Serous Ovarian Cancer

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.

Cost-effectiveness of maintenance hormonal therapy in patients with advanced low grade serous ovarian cancer

2021 ◽  
Vol 160 (1) ◽  
pp. 206-213
Author(s):  
Andra Nica ◽  
Ji Young Jennifer Lee ◽  
Nicole Look Hong ◽  
Taymaa May
Keyword(s):  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Hormonal Therapy ◽  
Low Grade ◽  
Serous Ovarian Cancer

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Li ◽  
Xue Cheng ◽  
Rong Rong ◽  
Yan Gao ◽  
Xiuwu Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Paraffin Section ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Systematic Analysis ◽  
Cox Regression Analysis ◽  
Genes Expression ◽  
High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

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