Evaluation of ex vivo drug combination optimization platform in recurrent high grade astrocytic glioma: An interventional, non-randomized, open-label trial protocol.

Introduction: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients.

A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).

Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA).

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

Background: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM.

Methods: Forty-four patients with GCPM received IP PTX (40 mg/m, Days 1, 8), oral capecitabine (1000 mg/m twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m, Day 1) in 21-day cycles.

Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.

Purpose: RET is an estrogen response gene with preclinical studies demonstrating cross-talk between the RET and estrogen receptor (ER) pathways. We investigate the role of lenvatinib, a multikinase inhibitor with potent activity against RET, in patients with metastatic breast cancer.

Patients And Methods: Patients with advanced ER+/HER2- breast cancer were treated with lenvatinib plus letrozole in a phase Ib/II trial.

A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours.

Background: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

Methods: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m, with or without sunitinib 12.

Third generation EGFR TKIs: current data and future directions.

Acquired T790 M mutation is the commonest cause of resistance for advanced non-small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutant patients who had progressed after first line EGFR TKI (tyrosine kinase inhibitor). Several third generation EGFR TKIs which are EGFR mutant selective and wild-type (WT) sparing were developed to treat these patients with T790 M acquired resistant mutation. Osimertinib is one of the third generation EGFR TKIs and is currently the most advanced in clinical development.

Development of PARP inhibitors in gynecological malignancies.

PARP inhibitors demonstrate synthetic lethality in tumors with BRCA1/2 mutations and other homologous recombination repair deficiencies by interfering with DNA repair and causing direct toxicity to DNA through PARP trapping. PARP inhibitors have been shown to be beneficial in the treatment of BRCA1/2-mutated ovarian cancers, which has led to a shift in the treatment paradigm of this disease. Further studies to establish the role of PARP inhibitors during earlier stages of treatment are ongoing.

Translating gastric cancer genomics into targeted therapies.

Gastric cancer is a common disease with limited treatment options and a poor prognosis. Many gastric cancers harbour potentially actionable targets, including over-expression and mutations in tyrosine kinase pathways. Agents have been developed against these targets with varying success- in particular, the use of trastuzumab in HER2-overexpressing gastric cancers has resulted in overall survival benefits.

Best practice in the treatment of advanced squamous cell lung cancer.

The management of advanced stage nonsmall cell lung cancer (NSCLC) has been altered by the recognition of histology-based treatment and the use of targeted therapy. Whilst outcomes have improved with adenocarcinoma, treatment options are still limited in advanced stage squamous cell lung cancer. With advances in the molecular characterization of squamous cell cancers (SCCs), new potential targets have been identified.

Record-based, stepwise screening for type 2 diabetes integrated into an annual cardiovascular care review system: Findings from a UK general practice.

Aims: Screening high-risk individuals for type 2 diabetes (T2DM) is recommended by many organisations. We report results from a pragmatic stepwise T2DM screening programme integrated into an annual review system in a UK general practice.

Methods: Patients with hypertension, cardiovascular disease or chronic kidney disease attending an annual review were screened for dysglycaemia by random blood glucose (RBG) measurement.

Noninvasive and invasive ventilation in acute respiratory failure associated with bronchiectasis.

Purpose: To describe the outcomes of patients with bronchiectasis and acute respiratory failure (ARF) treated with noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) after a failure of conservative measures, and to identify the predictors of hospital mortality and NIV failure.

Methods: Retrospective review of bronchiectatic patients on NIV (n = 31) or IMV (n = 26) for ARF over 8 years in a medical intensive care unit (ICU) experienced in NIV.

Results: At baseline, the NIV group had more patients with acute exacerbations without identified precipitating factors (87.