The selective outpatient treatment of adults with imported falciparum malaria: a prospective cohort study.

Background: Current UK malaria treatment guidelines recommend admission for all patients diagnosed with falciparum malaria. However, evidence suggests that certain patients are at lower risk of severe malaria and death and may be managed as outpatients.

Aim: To prospectively assess the risk of post-treatment severe falciparum malaria in selected cases managed as outpatients.

Sunitinib Treatment Exacerbates Intratumoral Heterogeneity in Metastatic Renal Cancer.

Purpose: The aim of this study was to investigate the effect of VEGF-targeted therapy (sunitinib) on molecular intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mccRCC).

Experimental Design: Multiple tumor samples (n = 187 samples) were taken from the primary renal tumors of patients with mccRCC who were sunitinib treated (n = 23, SuMR clinical trial) or untreated (n = 23, SCOTRRCC study). ITH of pathologic grade, DNA (aCGH), mRNA (Illumina Beadarray) and candidate proteins (reverse phase protein array) were evaluated using unsupervised and supervised analyses (driver mutations, hypoxia, and stromal-related genes).

Aspergillus-Specific Lateral-Flow Device and Real-Time PCR Testing of Bronchoalveolar Lavage Fluid: a Combination Biomarker Approach for Clinical Diagnosis of Invasive Pulmonary Aspergillosis.

Clinical experience with the impact of serum biomarkers for invasive fungal disease (IFD) varies markedly in hemato-oncology. Invasive pulmonary aspergillosis (IPA) is the most common manifestation, so we evaluated biomarkers in bronchoalveolar lavage (BAL) fluid. An Aspergillus-specific lateral-flow device (LFD), quantitative real-time PCR (qPCR), and the galactomannan (GM) test were used with 32 BAL fluid samples from 32 patients at risk of IPA.

Elevating the Horizon: Emerging Molecular and Genomic Targets in the Treatment of Advanced Urothelial Carcinoma.

Despite recent advances in the identification of genomic alterations that lead to urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas continue to have poor clinical outcomes. In the present review, we focus on targeted therapies that have yielded the most promising results alone or combined with traditional chemotherapy, including the antiangiogenesis agent bevacizumab, the human epidermal growth factor receptor 2 antibody trastuzumab, and the tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing clinical trials that use innovative approaches, including dose-dense scheduling of singular chemotherapy combinations, prospective screening of tumor tissues for mutational targets and biomarkers to predict chemosensitivity before the determination of the therapeutic regimen, and novel agents that target proteins in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD-1] and anti-PD-ligand 1) that have shown significant potential in preclinical models and early clinical trials.

Achieving Quality Assurance of Prostate Cancer Surgery During Reorganisation of Cancer Services.

Background: National Health Service England recently oversaw a whole-scale reconfiguration of cancer services in London, UK, for a number of different cancer pathways. Centralisation of cancer surgery has occurred with prostate cancer (PCa) surgery only being commissioned at a single designated pelvic cancer surgical centre. This process has required surgeons to work in teams providing a hub-and-spoke model of care.

Evaluating variation in use of definitive therapy and risk-adjusted prostate cancer mortality in England and the USA.

Objectives: Prostate cancer mortality (PCM) in the USA is among the lowest in the world, whereas PCM in England is among the highest in Europe. This paper aims to assess the association of variation in use of definitive therapy on risk-adjusted PCM in England as compared with the USA.

Design: Observational study.

Do prostate cancer risk models improve the predictive accuracy of PSA screening? A meta-analysis.

Background: Despite the extensive development of risk prediction models to aid patient decision-making on prostate screening, it is unknown whether these models could improve predictive accuracy of PSA testing to detect prostate cancer (PCa). The objective of this study was to perform a systematic review to identify PCa risk models and to assess the model's performance to predict PCa by conducting a meta-analysis.

Design: A systematic literature search of Medline was conducted to identify PCa predictive risk models that used at least two variables, of which one of the variables was prostate-specific antigen (PSA) level.

Development and validation of an ultra-high performance LC-MS/MS assay for intracellular SN-38 in human solid tumour cell lines: comparison with a validated HPLC-fluorescence method.

A simple and rapid ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) method has been developed for measuring intracellular concentrations of the anticancer agent 7-ethyl-10-hydroxycamptothecin (SN-38) in tumour cells using camptothecin (CPT) as internal standard. SN-38 extraction was carried out using acidified acetonitrile. SN-38 and CPT were separated on a PFP column using gradient elution with acidified water and acetonitrile.

A phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer.

Background: Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) inhibitor) demonstrate activity in metastatic clear cell renal cancer. The combination of these agents has a broad spectrum of relevant activity. The combination is explored in this phase Ib study.

Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and volume.

Purpose: Repeatability of baseline FDG-PET/CT measurements has not been tested in ovarian cancer. This dual-center, prospective study assessed variation in tumor 2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake, tumor diameter, and tumor volume from sequential FDG-PET/CT and contrast-enhanced computed tomography (CECT) in patients with recurrent platinum-sensitive ovarian cancer.

Experimental Design: Patients underwent two pretreatment baseline FDG-PET/CT (n = 21) and CECT (n = 20) at two clinical sites with different PET/CT instruments.

A C++ program to calculate sample sizes for cost-effectiveness trials in a Bayesian framework.

Cost-Effectiveness Analysis (CEA) has become an increasingly important component of clinical trials. However, formal sample size calculations for such studies are not common. One of the reasons for this might be due to the absence of readily available computer software to perform complex calculations, particularly in a Bayesian setting.

Whole blood stem cell reinfusion and escalated dose melphalan in castration-resistant prostate cancer: a phase 1 study.

Purpose: Nontaxane-based chemotherapeutic options in castrate-resistant prostate cancer (CRPC) are limited despite the long natural history of the disease. We carried out a phase 1 dose-escalation study of the alkylating agent melphalan with autologous stem cell transplantation, comparing rapid changes in circulating tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response.

Experimental Design: Cohorts of individuals with advanced CRPC received high-dose intravenous melphalan, and autologous blood was returned to patients during treatment.

Increased haematopoietic progenitor cells are associated with poor outcome in patients with metastatic renal cancer treated with sunitinib.

Background: Haematopoietic progenitor cells (HPCs) are present in blood in metastatic renal cell cancer (mRCC). We investigate their expression in mRCC patients treated with sunitinib and correlate their expression with plasma growth factor levels [insulin-like growth factor (IGF)-1].

Methods: Circulating HPCs (CD34(+)/CD45(+)) and plasma IGF-1 levels were measured at specific sequential time points (0, 6, 18 and 28 weeks) in 43 untreated mRCC patients receiving sunitinib (50 mg for 28 days followed by 14-day off treatment).

A synergistic interaction between lapatinib and chemotherapy agents in a panel of cell lines is due to the inhibition of the efflux pump BCRP.

Lapatinib is a specific HER1 and 2 targeted tyrosine kinase inhibitor now widely used in combination with chemotherapy in the clinical setting. In this work, we investigated the interactions between lapatinib and specific chemotherapy agents (cisplatin, SN-38, topotecan) in a panel of cell lines [breast (n = 2), lung (n = 2), testis (n = 4)]. A high-sensitivity cell proliferation/cytotoxicity ATP assay and flow cytometry were used to determine cell viability, apoptosis, and the effect of the drugs on cell-cycle distribution.

The relative activity of cisplatin, oxaliplatin and satraplatin in testicular germ cell tumour sensitive and resistant cell lines.

Background: Germ cell tumours (GCT) can become resistant to cisplatin, which is associated with a relatively poor prognosis. Oxaliplatin and satraplatin have been developed to overcome cisplatin resistance in other cancers, but their effect in cisplatin resistant (cisR) GCTs is unclear. In this work we address this issue by comparing their efficacy in three paired sensitive and cisR GCT cell lines.