High-grade Serous Ovarian Cancer Research Articles

3D organoid models for predicting drug response in platinum-sensitive, high-grade serous ovarian cancer

3D organoid models for predicting drug response in platinum-sensitive, high-grade serous ovarian cancer

Homologous recombination status in BRCA wild-type patients as a predictor of disease volume and surgical outcome in patients with high-grade serous ovarian cancer

Homologous recombination status in BRCA wild-type patients as a predictor of disease volume and surgical outcome in patients with high-grade serous ovarian cancer

Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

Use of DNA methyltransferase inhibitor and poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) in the treatment of PARPi-resistant, high-grade serous ovarian cancer

Use of DNA methyltransferase inhibitor and poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) in the treatment of PARPi-resistant, high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Efficacy and safety of alpelisib plus olaparib versus chemotherapy among patients with platinum-resistant or refractory high-grade serous ovarian cancer without BRCA mutation: Primary analysis of the EPIK-O trial

Efficacy and safety of alpelisib plus olaparib versus chemotherapy among patients with platinum-resistant or refractory high-grade serous ovarian cancer without BRCA mutation: Primary analysis of the EPIK-O trial

Does cancer appearance reflect genetic status? The relationship between the gross appearance of high-grade serous ovarian cancer and BRCA mutation status

Does cancer appearance reflect genetic status? The relationship between the gross appearance of high-grade serous ovarian cancer and BRCA mutation status

Association of high-grade serous ovarian cancer sample clonality with clinical outcomes

Association of high-grade serous ovarian cancer sample clonality with clinical outcomes

Impact of the tumor microenvironment in splenic metastasis in high-grade serous ovarian cancer revealed by quantitative proteomics

Impact of the tumor microenvironment in splenic metastasis in high-grade serous ovarian cancer revealed by quantitative proteomics

Focal adhesion kinase inhibitors as maintenance therapy in a homologous recombination repair proficient high-grade serous ovarian cancer murine model

Focal adhesion kinase inhibitors as maintenance therapy in a homologous recombination repair proficient high-grade serous ovarian cancer murine model

P53 functional status is associated with survival among high-grade serous ovarian cancer patients with copy number signature one

p53 functional status is associated with survival among high-grade serous ovarian cancer patients with copy number signature one

A spatial proteomic study of platinum-refractory, high-grade serous ovarian cancer implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment

A spatial proteomic study of platinum-refractory, high-grade serous ovarian cancer implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment

Spatial transcriptomics characterizes high-grade serous ovarian cancer and its precursor lesions

Spatial transcriptomics characterizes high-grade serous ovarian cancer and its precursor lesions

RAS/RAF/MEK mutated high-grade serous ovarian cancer susceptible to Raf inhibition in vitro but not in vivo

RAS/RAF/MEK mutated high-grade serous ovarian cancer susceptible to Raf inhibition in vitro but not in vivo

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71years) and 77years (IQR 70-82years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25months and 23months, respectively (p = 0.38) with a median follow-up of 20months (IQR 11-29months). The 1year disease-specific mortality for both groups was 18%. Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Prognostic factors and overall survival among patients with ovarian cancer in the pre-PARP inhibitor era: the OCRWE-Finland study.

Despite recent treatment advances in ovarian cancer (OC), more real-world evidence studies investigating patient outcomes are needed. OCRWE-Finland was an observational cohort study investigating OC outcomes in Finland during the pre-PARP inhibitor era. Patients were diagnosed with OC between 2014 and 2019 in Finland. This analysis reports baseline characteristics of all patients, patients with high-grade serous OC (HGSOC), and overall survival (OS) for patients with HGSOC. Among 1,711 patients diagnosed with OC, 867 (51%) had HGSOC. The absence versus presence of visible residual disease post-debulking surgery was associated with improved OS for patients at stage III (n = 303; median: NR vs. 43 months; p = 0.005), but not stage IV (n = 118; median: 37 months vs. 40 months; p = 0.96). Bevacizumab treatment at any line at stages III/IV improved OS in the short-term only. Receiving versus not receiving bevacizumab at first-line for patients with visible residual disease post-debulking surgery was associated with improved OS at stage III (median: 48 months vs. 36 months; p = 0.003), but not stage IV (median: 42 months vs. 37 months; p = 0.26). Multivariate Cox regression analyses showed that stage IV at initial diagnosis and the presence of R2 classification post-debulking surgery resulted in poorer OS. In the pre-PARP inhibitor era, the absence versus presence of visible residual disease post-debulking surgery was associated with improved OS in stage III, but not stage IV HGSOC. First-line bevacizumab seemed to be beneficial in patients with stage III HGSOC and visible residual disease.

Developing a DNA Methylation Signature to Differentiate High-Grade Serous Ovarian Carcinomas from Benign Ovarian Tumors.

Epithelial ovarian cancer (EOC) represents a significant health challenge, with high-grade serous ovarian cancer (HGSOC) being the most common subtype. Early detection is hindered by nonspecific symptoms, leading to late-stage diagnoses and poor survival rates. Biomarkers are crucial for early diagnosis and personalized treatment OBJECTIVE: Our goal was to develop a robust statistical procedure to identify a set of differentially methylated probes (DMPs) that would allow differentiation between HGSOC and benign ovarian tumors. Using the Infinium EPIC Methylation array, we analyzed the methylation profiles of 48 ovarian samples diagnosed with HGSOC, borderline ovarian tumors, or benign ovarian disease. Through a multi-step statistical procedure combining univariate and multivariate logistic regression models, we aimed to identify CpG sites of interest. We discovered 21 DMPs and developed a predictive model validated in two independent cohorts. Our model, using a distance-to-centroid approach, accurately distinguished between benign and malignant disease. This model can potentially be used in other types of sample material. Moreover, the strategy of the model development and validation can also be used in other disease contexts for diagnostic purposes.

Robotic Rectosigmoid Resection with Totally Intracorporeal Colorectal Anastomosis (TICA) for Recurrent Ovarian Cancer: A Case Series and Description of the Technique.

Most patients with ovarian cancer relapse within 2 years. Prospective randomized trials, such as DESKTOP III and SOC-I, have shown the role of secondary cytoreduction in improving oncological outcomes in selected patients, when complete tumor resection is achieved. Recent retrospective series suggest that minimally invasive surgery is a feasible option in oligometastatic recurrences, such as rectal ones. Five patients with an isolated rectal recurrence infiltrating the bowel wall underwent a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis. The procedure began with retroperitoneal access to manage the vascular structures, followed by visceral resection with a minimally invasive approach. The standard steps of an en-bloc pelvic resection, including intracorporeal end-to-end anastomosis, were performed. The treatment data were evaluated. The mean age of the patients was 54 years, and their mean body mass index was 30. All patients had at least one previous abdominal surgery and 60% had high-grade serous ovarian cancer at their initial diagnosis. Their mean platinum-free interval was 17.4 months. Complete secondary cytoreduction was achieved in all cases, with histopathology confirming bowel infiltration. The mean procedure duration was 294 min, with an estimated blood loss of 180 mL. No intraoperative complications occurred. The mean hospital stay was 8 days. One patient had a grade 2 postoperative complication. The mean follow-up period was 14 months, with only one patient experiencing a recurrence at the level of the abdominal wall. Robotic rectosigmoid resection is a viable option for complete cytoreduction in isolated recurrent ovarian cancer.

Metabolomic Analysis of Histological Composition Variability of High-Grade Serous Ovarian Cancer Using 1H HR MAS NMR Spectroscopy.

In this work, the HR MAS NMR (high-resolution magic-angle spinning nuclear magnetic resonance) spectroscopy technique was combined with standard histological examinations to investigate the metabolic features of high-grade serous ovarian cancer (HGSOC) with a special focus on the relation between a metabolic profile and a cancer cell fraction. The studied group consisted of 44 patients with HGSOC and 18 patients with benign ovarian tumors. Normal ovarian tissue was also excised from 13 control patients. The metabolic profiles of 138 tissue specimens were acquired on a Bruker Avance III 400 MHz spectrometer. The NMR spectra of the HGSOC samples could be discriminated from those acquired from the non-transformed tissue and were shown to depend on tumor purity. The most important features that differentiate the samples with a high fraction of cancer cells from the samples containing mainly fibrotic stroma are the increased intensities in the spectral regions corresponding to phosphocholine/glycerophosphocholine, phosphoethanolamine/serine, threonine, uridine nucleotides and/or uridine diphosphate (UDP) nucleotide sugars. Higher levels of glutamine, glutamate, acetate, lysine, alanine, leucine and isoleucine were detected in the desmoplastic stroma within the HGSOC lesions compared to the stroma of benign tumors. The HR MAS NMR analysis of the metabolic composition of the epithelial and stromal compartments within HGSOC contributes to a better understanding of the disease's biology.

The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions.

Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.