Niraparib as First-Line Maintenance Therapy in Patients with Stage III Ovarian Cancer and No Visible Residual Disease: AR1ZE Real-World Study.

Introduction: Niraparib was approved for first-line (1L) maintenance (1LM) treatment of patients with advanced epithelial ovarian cancer (EOC) following the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial. PRIMA was restricted to patients at higher risk of progression (excluded stage III EOC with no visible residual disease [NVRD] after primary cytoreductive surgery [PCS]). This retrospective study evaluated the potential impact of excluding stage III EOC with NVRD from PRIMA by assessing real-world treatment outcomes following 1LM niraparib monotherapy in this patient population.

Granulomatosis with polyangiitis with cardiac and large vessel involvement: a case report with a constellation of rare complications.

Background: Granulomatosis with polyangiitis (GPA) is an autoimmune multisystem disorder characterized by small vessel vasculitis with granulomatous inflammation. In this report, we describe a unique case of GPA who presented with complete heart block (CHB) and developed complications due to intracranial large vessel involvement.

Case Summary: A 47-year-old gentleman presented with CHB with a background history of arthralgia and blood-tinged nasal discharge.

Clinical trial screening in gynecologic oncology: Defining the need and identifying best practices.

Background: Evidence is limited in gynecologic cancers on best practices for clinical trial screening, but the risk of ineffective screening processes and subsequent under-enrollment introduces significant cost to patient, healthcare systems, and scientific advancement. Absence of a defined screening process makes determination of who and when to screen potential patients inconsistent allowing inefficiency and potential introduction of biases. This is especially germane as generative artificial intelligence (AI), and electronic health record (EHR) integration is applied to trial screening.

The Role of the Public Health Workforce in Securing Political Commitment for Tackling Childhood Obesity in Local Government.

Local government is well placed to provide leadership for the national ambition in England to halve childhood obesity by 2030 and has delegated authority for many policies thought necessary for effective action. However, with currently constrained local government finances, resources may not be prioritized for the wide range of policies and interventions necessary. Thus, local political commitment is vital for directing local government investment to tackle the issue.

Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Objectives: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

Methods: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years.

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer.

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection.

Standard of care treatment for stage IVB cervical cancer: A systematic review and meta-analysis.

Objective: Our aim was to perform a systematic review and meta-analysis evaluating the efficacy of standard treatment for stage IVB cervical cancer.

Method: Databases were searched for Phase III trials evaluating stage IVB CC patients according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Systematic review included Phase III trials evaluating first-line treatment of stage IVB cervical cancer (CC).

Patient-reported outcomes in the subpopulation of patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy compared with chemotherapy alone in the ENGOT-EN6-NSGO/GOG3031/RUBY trial.

Objective: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial.

Methods: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression.

Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

Background: The phase III PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

Introduction: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy.

Methods: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy.

Prescribers and patients drive maintenance therapy patterns in a community oncology practice: National guidelines versus the real-world experience.

Objective: Previous studies have shown that first-line (1L) maintenance therapy (MT) with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab improves outcomes among patients with advanced ovarian cancer (OC); however, these treatments are underutilized. This study aimed to provide a real-world understanding of MTs among patients with advanced OC who received 1L platinum-based chemotherapy (PBC).

Methods: A retrospective chart review using iKnowMed electronic health records to identify patients aged ≥18 years with advanced OC who initiated 1L PBC between January 1, 2018-December 31, 2020.

Dostarlimab for the Treatment of Endometrial Cancer: A Review.

There have been many recent changes in the treatment of endometrial cancer, most recently with the US Food and Drug Administration's (FDA) approval of dostarlimab in conjunction with standard-of-care chemotherapy in the frontline setting for mismatch repair-deficient (dMMR) populations. This review sought to summarize the publications and studies that have led to this practice-changing approval. Dostarlimab is an immune checkpoint inhibitor with a favourable safety profile and proven efficacy in the treatment of endometrial cancer, particularly dMMR endometrial cancer.

A systematic review of stage IVA cervical cancer treatment: Challenges in the management of an understudied group.

Objective: Stage IVA patients comprise a small proportion of participants in cervical cancer trials, yet survival outcomes are disproportionately poor. We aim to perform a systematic review evaluating stage IVA cervical cancer.

Methods: This systematic review was completed via PRISMA 2020 guidelines using two databases.

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification.

Purpose: Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity.

The impact of varying levels of residual disease following cytoreductive surgery on survival outcomes in patients with ovarian cancer: a meta-analysis.

Background: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease.

Methods: Medline, Embase, and Cochrane databases (January 2011 - July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies.

Randomized Controlled Trial of Durotomy as an Adjunct to Routine Decompressive Surgery for Dogs With Severe Acute Spinal Cord Injury.

Although many interventions for acute spinal cord injury (SCI) appear promising in experimental models, translation directly from experimental animals to human patients is a large step that can be problematic. Acute SCI occurs frequently in companion dogs and may provide a model to ease translation. Recently, incision of the dura has been highlighted in both research animals and human patients as a means of reducing intraspinal pressure, with a view to improving perfusion of the injured tissue and enhancing functional recovery.

Cytochrome P450 inhibitor/inducer treatment patterns among patients in the United States with advanced ovarian cancer who were prescribed or were eligible for poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors in the first-line maintenance setting.

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC.

Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.

Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases.

Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

Objective: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy.

Methods: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death.

Telephone Health Coaching and Remote Exercise Monitoring (TeGeCoach) in Peripheral Arterial Occlusive Disease—a Randomized Controlled Trial.

Background: Supervised exercise programs are used to treat intermittent claudication (IC). Home-based exercise programs have been developed to lower barriers to participation. We studied the effects of one such exercise program (TeGeCoach) on self-reported walking ability in patients with IC.

Projected health and economic effects of the increase in childhood obesity during the COVID-19 pandemic in England: The potential cost of inaction.

Background: The prevalence of overweight and obesity in young children rose sharply during the COVID-19 pandemic. Here we estimate the potential future health and economic effects of these trends in England.

Methods: Using publicly available annual Body Mass Index (BMI) data from 2006-2022, we calculated the increase in overweight/obesity prevalence (BMI ≥85th reference percentile) during the COVID-19 pandemic among children aged 4-5 and 10-11, and variation by deprivation and ethnicity.