Overall survival (OS) in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy: An interim analysis.

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

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Salvage radiation therapy for localized recurrent ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000247 ◽

2019 ◽

Vol 29 (5) ◽

pp. 916-921

Author(s):

Alicia Smart ◽

Yu-Hui Chen ◽

Teresa Cheng ◽

Martin King ◽

Larissa Lee

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Clear Cell ◽

Recurrent Ovarian Cancer ◽

Salvage Radiotherapy ◽

Platinum Sensitive ◽

Long Term Survivors ◽

Disease Free

IntroductionTo evaluate clinical outcomes for patients with localized recurrent ovarian cancer treated with salvage radiotherapy.MethodsIn a retrospective single institutional analysis, we identified 40 patients who received salvage radiotherapy for localized ovarian cancer recurrence from January 1995 to June 2011. Recurrent disease was categorized as: pelvic peritoneal (45%, 18), extraperitoneal/nodal (35%, 14), or vaginal (20%, eight). Actuarial disease-free and overall survival estimates were calculated by Kaplan–Meier and prognostic factors evaluated by the Cox proportional hazards model.ResultsMedian follow-up was 42 months. Median patient age was 54 years (range, 27–78). Histologic subtypes were: serous (58%, 23), endometrioid (15%, six), clear cell (13%, five), mucinous (8%, three), and other (8%, three). At the time of salvage radiotherapy, surgical cytoreduction was performed in 60% (24) and 68% (27) had platinum-sensitive disease. Most patients (63%, 25) received salvage radiotherapy at the time of first recurrence. Relapse after salvage radiotherapy occurred in 29 patients at a median time of 16 months and was outside the radiotherapy field in 62%. 18 At 3 years, disease-free and overall survival rates were 18% and 80%, respectively. On multivariate analysis, non-serous histology (hazards ratio 0.3, 95% CI 0.1–0.7) and platinum-sensitivity (hazards ratio 0.2, 95% CI 0.1–0.5) were associated with lower relapse risk. Platinum-sensitivity was also associated with overall survival (hazards ratio 0.4, 95% CI 0.1–1.0). Four patients (10%) were long-term survivors without recurrence 5 years after salvage radiotherapy. Of the five patients with clear cell histology, none experienced relapse at the time of last follow-up.DiscussionPatients with non-serous and/or platinum-sensitive ovarian cancer had the greatest benefit from salvage radiotherapy for localized recurrent disease. Although relapse was common, radiotherapy prolonged recurrence for > 1 year in most patients and four were long-term survivors.

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KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01775-9 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Marta De Donato ◽

Gabriele Babini ◽

Simona Mozzetti ◽

Marianna Buttarelli ◽

Alessandra Ciucci ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Prognostic Marker ◽

Late Stage ◽

Therapeutic Target ◽

Family Members ◽

High Grade ◽

Serous Ovarian Cancer

Abstract Background In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way. Methods To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors. Results Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction. Conclusions Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.

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Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000672 ◽

2016 ◽

Vol 26 (4) ◽

pp. 671-679 ◽

Cited By ~ 28

Author(s):

Hans-Christian Bösmüller ◽

Philipp Wagner ◽

Janet Kerstin Peper ◽

Heiko Schuster ◽

Deborah Lam Pham ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Clinical Outcome ◽

Prognostic Value ◽

Intraepithelial Lymphocytes ◽

High Grade ◽

Serous Ovarian Cancer ◽

Term Survival ◽

Cell Counts

ObjectiveIncreased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103+ TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC.MethodsThe density of intratumoral CD3+ and CD103+ lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4+, CD8+, CD56+, FoxP3+, and TCRγ+ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome.ResultsBoth the presence of CD103+ cells, as well as high numbers of intraepithelial CD3+ lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3high/CD103high tumors showed a 5-year survival rate at 90%, CD3low/CD103high at 63%, and CD3low/CD103low at 0% (P < 0.001).ConclusionsThese results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.

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