These findings will enable rational design of clinical trials aimed at combinatorial approaches to improve chemotherapy response and survival in HGSC patients.

High-grade serous ovarian cancer remains one of the most lethal malignancies in women. Despite recent advances in surgical and pharmaceutical therapies, survival rates remain poor. A major impediment in management of this disease, that continues to contribute to poor overall survival rates, is resistance to standard carboplatin-paclitaxel combination chemotherapies. In addition to tumor cell intrinsic mechanisms leading to drug resistance, there is increasing awareness of the crucial role of the tumor microenvironment in mediating natural immune defense mechanisms and selective pressures that appear to facilitate chemotherapy sensitivity. We provide an overview of some of the promising new genetic and immunological biomarkers in ovarian cancer and discuss their biology and their likely clinical utility in future ovarian cancer management.

High‐grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8+ T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8+ T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy‐naïve HGSCs. NanoString‐based profiling was performed to correlate expression of STAT1 target genes CXCL9, CXCL10 and CXCL11 with CD8A transcript expression in 143 primary tumours. Multiplexed cytokine analysis of pre‐treatment plasma from resistant and sensitive patients was performed to assess systemic levels of STAT1‐induced cytokines. STAT1 was validated as a prognostic and predictive biomarker in both univariate and multivariate models and its expression correlated significantly with intra‐epithelial CD8+ T cell infiltration in HGSC. STAT1 levels increased the prognostic and predictive value of intratumoural CD8+ T cells, confirming their synergistic role as biomarkers in HGSC. In addition, expression of STAT1 target genes (CXCL9, CXCL10 and CXCL11) correlated significantly with levels of, and CD8A transcripts from intratumoural CD8+ T cells within the resistant and sensitive tumours. Our findings provide compelling evidence that high levels of STAT1, STAT1‐induced chemokines and CD8+ T cells correlate with improved chemotherapy response in HGSC. These results identify STAT1 and its target genes as novel biomarkers of chemosensitivity in HGSC. These findings provide new translational opportunities for patient stratification for immunotherapies based on emerging biomarkers of inflammation in HGSC. An improved understanding of the role of interferon‐inducible genes will be foundational for developing immunomodulatory therapies in ovarian cancer.

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Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery. In this review, we highlight the most significant contributions of omics approaches and how the advent of immunomics can aid in personalized combination chemo-immunotherapy in ovarian cancer treatment. We further provide insights into immunogenomic correlates of pre-treatment tumour immune microenvironment and some of the potential interpretations of immunomic data that require further validation, based on stromal and immune contributions to biomarker signatures. We believe a comprehensive integrative approach via meta-analysis of large ovarian cancer molecular profiling data sets is urgently needed to define robust prognostic and predictive classifiers of disease progression and treatment response. These investigations will inform rationalized biomarker-driven combination chemo-immunotherapy trials for improving response and survival of ovarian cancer patients.

Objective The purpose of this guideline is to recommend systemic therapy options for women with recurrent epithelial ovarian cancer, including fallopian tube and primary peritoneal cancers. Methods This document updates the recommendations published in the 2011 Optimal Chemotherapy forRecurrent Ovarian Cancer guideline from Cancer Care Ontario. Draft recommendations were formulated based on evidence obtained through a systematic review of phase ii and iii randomized controlled trials (rcts). The draft recommendations underwent internal review by clinical and methodology experts, and external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. ResultsThe primary literature search yielded thirty-six primary research papers representing thirty rcts that met the eligibility criteria. The guideline provides recommendations for patients with serous tumour histologies and with recurrent, platinum-resistant, and platinum-sensitive ovarian cancer. ConclusionsThe body of evidence from trials that included olaparib and bevacizumab consistently shows a benefit in progression-free survival (pfs) without a corresponding benefit in overall survival (os). The Working Group for this guideline designated pfs, which is associated with symptom control, as a critical outcome. A finding of net benefit can therefore be concluded based on significant differences in pfs. However, that benefit is not without identified harms. Given the identified harms, patient involvement in the decision-making process must take into consideration the side effect profiles of olaparib and bevacizumab within the context of improved pfs but minimal change in os.

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