Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.

The VALTIVE1 study protocol: a study for the validation of Tie2 as the first tumour vascular response biomarker for VEGF inhibitors.

Background: Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene.

Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.

Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.

Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial.

Objective: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction.

Methods: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction.

Real-World Concordance between Germline and Tumour Status in Epithelial Ovarian Cancer.

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour / testing followed by germline testing in patients with a positive tumour test result. This testing model relies on tumour / tests being able to detect all types of pathogenic variant. We analysed germline and tumour test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre.

Unexpected Diastereomer Formation and Interconversions in Cyclohexane-1,2-diacetal Derivatization of a Glucuronic Acid Thioglycoside.

Reactions of a glucuronic acid (GlcA) β-thioglycoside with cyclohexadione show initial formation of the two anticipated all-trans decalin-type O2,O3 and O3,O4 cyclohexane-1,2-diacetals (CDAs) along with an epimer of the main O2,O3 acetal. This trans-cis isomer is then interconverted leading to higher amounts of the two all-trans products. Isomerization studies indicate slow interconversion between the all-trans CDA acetals, with only one undergoing significant interconversion with the minor 2,3-diastereomer.

Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial.

Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.

Patients And Methods: Phase II trial with two entry points (EP1, EP2).

Is Reflex Germline Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour / variants. The value of germline testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour testing by the North West of England Genomic Laboratory Hub.

Home Parenteral Nutrition in Patients with Advanced Cancer: Quality Outcomes from a Centralized Model of Care Delivery.

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010-2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area.

Predicting the likelihood of a pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.

Aims: Clinical guidelines recommend testing both germline and tumour DNA for pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline PVs.

Methods: An observational study that included all tumour PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022.

Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.

Background: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment.

BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (n = 388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.

c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial.

Introduction: Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 (ClinicalTrials.

Psychosexual Morbidity in Women With Ovarian Cancer: Evaluation by Germline BRCA Gene Mutational Status.

Introduction: Up to 75% of women with ovarian cancer experience psychosexual morbidity and approximately 15-20% of women with ovarian cancer have a germline BRCA1/2 mutation (gBRCAm). However, psychosexual morbidity remains unexplored in women with gBRCAm ovarian cancer.

Aim: Given their younger age, genetic diagnosis, breast cancer risk, and increased prevalence of surgically-induced menopause, we aim to assess whether women with gBRCAm ovarian cancer experience distinct psychosexual morbidity.

Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial.

Background: Treatment outcomes remain poor in recurrent platinum-resistant ovarian cancer. Enadenotucirev, a tumor-selective and blood stable adenoviral vector, has demonstrated a manageable safety profile in phase 1 studies in epithelial solid tumors.

Methods: We conducted a multicenter, open-label, phase 1 dose-escalation and dose-expansion study (OCTAVE) to assess enadenotucirev plus paclitaxel in patients with platinum-resistant epithelial ovarian cancer.

The role of vascular endothelial growth factor inhibitors in the treatment of epithelial ovarian cancer.

Advanced epithelial ovarian, fallopian tube and primary peritoneal cancers (EOC) are a leading cause of gynaecological cancer-associated mortality and angiogenesis plays a key role in their growth. Vascular endothelial growth factor inhibitors (VEGFi) disrupt angiogenesis and improve the response rate, progression-free survival and in some cases, overall survival, when administered with and following cytotoxic chemotherapy, irrespective of the platinum sensitivity of EOC. Recent data have identified new indications for VEGFi in EOC: repeated exposure to VEGFi in the first- and then second-line treatment has sustained clinical efficacy; combinations of VEGFi with poly (ADP-ribose) polymerase inhibitors (PARPi) have proven effective as first-line or second-line maintenance regimens.

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study.

Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone.

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial.

Background: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS).

Patients And Methods: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance).

Image Contrast, Image Pre-Processing, and T Mapping Affect MRI Radiomic Feature Repeatability in Patients with Colorectal Cancer Liver Metastases.

Imaging biomarkers require technical, biological, and clinical validation to be translated into robust tools in research or clinical settings. This study contributes to the technical validation of radiomic features from magnetic resonance imaging (MRI) by evaluating the repeatability of features from four MR sequences: pre-contrast T1- and T2-weighted images, pre-contrast quantitative T1 maps (qT1), and contrast-enhanced T1-weighted images. Fifty-one patients with colorectal cancer liver metastases were scanned twice, up to 7 days apart.

Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial.

Background: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported.

Psychosexual morbidity in women with ovarian cancer.

Increasing numbers of women are surviving for longer with epithelial ovarian cancer. Consequently, there is increased focus on long-term quality of life in national guidance. Psychosexual morbidity including vaginal dryness, pain during intercourse (dyspareunia), reduced libido, and negative perceived body image exacerbate stress and anxiety and impact intimate relationships.

ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy.

Background: Two novel biological agents-cediranib targeting angiogenesis, and olaparib targeting DNA repair processes-have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy.

Primary Objective: To assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse.