Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study.

Purpose: The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor, prevents oestrogen resistance in animal models and reduces osteoclast activity. We aimed to evaluate the efficacy of saracatinib addition to aromatase inhibitors (AI) in patients with hormone receptor-positive metastatic breast cancer.

Total Pelvic Exenteration surgery - Considerations for healthcare professionals.

Background: Associated with considerable risk of morbidity, Total Pelvic Exenteration (TPE) is a life-altering procedure involving a significant prolonged recovery. As a result, and with the view of achieving the best outcomes and lessen short and long-term morbidities, a well-thought-out and coordinated multidisciplinary team approach, is crucial to the provision of safe and high-quality care.

Method: Using a nominal group technique and qualitative methodology, this article explores the current practices in the care of oncology patients who undergo TPE surgery, in a tertiary cancer centre, by highlighting considerations of a collaboratively multi-disciplinary team.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial.

Background: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8.

Cost-effectiveness analysis of the Oncotype DX Breast Recurrence Score test in node-positive early breast cancer.

Aims: Given the high rate of adverse events and high cost of adjuvant chemotherapy, it is optimal to avoid its use when endocrine therapy is equally effective at preventing distant recurrence of early breast cancer. The Oncotype DX test is a predictive and prognostic multigene assay used to guide adjuvant chemotherapy decisions in early breast cancer based on a Recurrence Score (RS) result. A model-based cost-effectiveness analysis compared the Oncotype DX test to clinical risk tools alone for HR+/HER2- node-positive (1-3 axillary lymph nodes) early breast cancer patients based on results from the RxPONDER trial.

Breast tumour volume and blood flow measured by MRI after one cycle of epirubicin and cyclophosphamide-based neoadjuvant chemotherapy as predictors of pathological response.

Objectives: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response.

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).

Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial.

Background: The ICON8 study reported no significant improvement in progression-free survival (a primary endpoint) with weekly chemotherapy compared with standard 3-weekly treatment among patients with epithelial ovarian cancer. All ICON8 patients were eligible to take part in the accompanying health-related quality-of-life study, which measured the effect of treatment on self-reported wellbeing, reported here.

Methods: In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC-IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m paclitaxel weekly).

Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7).

Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months).

Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre.

Background: Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies.

Methods: Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012-March 2018.

Results: One hundred ninety-six women were identified with HR+/HER2- MBC.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.

Background: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study.

Objective: Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK.

Methods: Between May 2013 and April 2015, patients with high-risk stage IIIB-IV advanced ovarian cancer received bevacizumab (7.

High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum.

Background: Approximately half of high-grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency.

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.

Objectives: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.

Methods: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease.

Long-term outcome after surgical treatment of intra-articular tibial plateau fractures in skiers.

Introduction: Tibial plateau fractures occur frequently during downhill skiing. There is a lack of information about the outcome and development of posttraumatic osteoarthritis after internal fixation of such fractures at long-term follow-up in skiers.

Materials And Methods: A population of 83 skiers was followed up in a case series after internal fixation of intra-articular tibial plateau fractures AO-OTA 41 B1-B3 and C1-C3.

Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer.

Objective: In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease.

Methods: Patients with stage IIB-IV or high-risk (grade 3/clear-cell) stage I-IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.

Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials.

Background: Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations.

Methods: We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma.

A functional form for a representative individual arterial input function measured from a population using high temporal resolution DCE MRI.

Purpose: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted.

Methods: Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer.

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests.

Long-term radiographic appearance of calcium-phosphate synthetic bone grafts after surgical treatment of tibial plateau fractures.

Objectives: Synthetic bone grafts (SBGs) are widely used to fill bone defects after fracture reduction. This study assessed the long-term resorption of two different calcium phosphate products (A=ChronOS™ inject and B=Norian SRS; both DePuy Synthes, Oberdorf, Switzerland) used in the surgical treatment of tibial plateau fractures.

Design: Long-term clinical and radiologic follow-up of 52 patients after surgical treatment of intraarticular tibial plateau fractures augmented with SBGs.

Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes.

Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer. DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial.

30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study.

Background: 30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved.

Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK.

Aims: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally.

Materials And Methods: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL).

The Cost-Effectiveness of Bevacizumab in Advanced Ovarian Cancer Using Evidence from the ICON7 Trial.

Background: Bevacizumab is used extensively in the treatment of cancer, including advanced ovarian cancer, for which results of the International Collaborative Ovarian Neoplasm (ICON) 7 trial have been recently reported. The National Institute for Health and Care Excellence's (NICE's) recent decision not to recommend bevacizumab for advanced ovarian cancer was not based on evidence related to the unlicensed lower dosage (7.5 mg/kg) of the drug despite its use in the English National Health Service (NHS) and the ICON7 trial.