Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK.

Introduction: Head and neck cancer is the eighth most common cancer in the UK. Current standard of care treatment for patients with recurrent/metastatic squamous cell head and neck carcinoma (HNSCC) is platinum-based chemotherapy combined with the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, cetuximab. However, most patients will have poor median overall survival (OS) of 6-9 months despite treatment.

Old Age Psychiatry.

Objective: Older Chinese people in New Zealand underutilise mental health services. Lack of recognition of mental health issues and awareness of available treatment is a potential barrier to accessing care. This study investigated depression literacy in older Chinese people.

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer.

Background: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC).

Methods: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

Purpose: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.

Materials And Methods: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC).

Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia.

Purpose: Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL.

Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.

Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients with neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffin-embedded (FFPE), and fresh frozen (FF) samples.

Ketonuria and Seizure Control in the Medium Chain Triglyceride and Classic Ketogenic Diets.

We hypothesized that children receiving medium-chain triglyceride ketogenic diet (MCTKD) experience similar seizure reduction despite lower ketosis compared with classic ketogenic diet (CKD). Children initiating CKD or MCTKD were enrolled in a prospective observational study. Forty-five children completed 6 months of KD (n = 17 MCTKD, n = 28 CKD).

Neutropenia in Children Treated With Ketogenic Diet Therapy.

Objectives: The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy.

Methods: A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed.

Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors.

Background: Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined.

Objective: This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs.

Patients And Methods: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109).

Development of a novel patient focussed symptom severity index for use in assessing and treating inflammatory conditions of the lactating breast: a Delphi study.

Aim: To investigate the content and face validity of a patient-reported outcome measure used by Australian physiotherapists in the assessment of inflammatory conditions of the lactating breast.

Methods: Sixty one experts representing 'women who previously had inflammatory conditions of the lactating breast' (48%), 'clinicians' (38%) and 'academics' (8%) interested in women's health and 7% unidentified participants were invited to complete a three round Delphi study.

Results: Ninety five percent of participants agreed that overall, the patient-reported outcome measure was appropriate for use in assessing and treating inflammatory conditions of the lactating breast.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

Background: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required.

Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours.

Background: Bone metastases are associated with a worse outcome in patients with neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive of skeletal involvement. We investigated the role of circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors of skeleton invasion.

Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

This corrects the article DOI: 10.1038/nature22364.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study.

Tracking the Evolution of Non-Small-Cell Lung Cancer.

Background: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.

Methods: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy.

Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours.

Background: Neuroendocrine tumours (NET) overexpress somatostatin receptors (SSTR) that can be targeted for therapy. Somatostatin receptor expression is routinely measured by molecular imaging but the resolution is insufficient to define heterogeneity. We hypothesised that SSTR expression could be measured on circulating tumour cells (CTCs) and used to investigate heterogeneity of expression and track changes during therapy.

GPs' perspectives on managing the NHS Health Check in primary care: a qualitative evaluation of implementation in one area of England.

Objectives: To evaluate the implementation of the National Health Service (NHS) Health Check programme in one area of England from the perspective of general practitioners (GPs).

Design: A qualitative exploratory study was conducted with GPs and other healthcare professionals involved in delivering the NHS Health Check and with patients. This paper reports the experience of GPs and focuses on the management of the Heath Check programme in primary care.

Enumeration and Molecular Characterisation of Circulating Tumour Cells in Endometrial Cancer.

Background: This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC).

Method: Between October 2012 and February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform.

Early Changes in Circulating Tumor Cells Are Associated with Response and Survival Following Treatment of Metastatic Neuroendocrine Neoplasms.

Purpose: To investigate posttreatment circulating tumor cell (CTC) counts in patients with neuroendocrine neoplasms (NENs) as a predictive biomarker for disease progression and overall survival (OS).

Experimental Design: Patients with metastatic NENs commencing therapy were prospectively recruited (n = 138). Blood samples were obtained for evaluation of CTCs using the CellSearch platform and for chromogranin A (CgA) at baseline, three to five (median, 4.

A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer.

We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days.

Can children with hyperlipidemia receive ketogenic diet for medication-resistant epilepsy?

The very-high-fat ketogenic diet can worsen lipid levels in children with pre-existing hyperlipidemia by increasing serum lipoproteins and reducing antiatherogenic high-density lipoproteins. A retrospective chart review of 160 children treated with the ketogenic diet from September 2000 to May 2011 was performed. Twelve children with pre-existing hyperlipidemia were identified.

Evidence for different mechanisms of 'unhooking' for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples.

Background: DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy.

Voice familiarity engages auditory cortex.

Familiarity with a speaker's voice has been shown to enhance its auditory processing, implicating physiological effects at the level of the auditory cortex, although auditory cortical involvement has not previously been demonstrated. Eleven healthy right-handed male participants performed two tasks during blood oxygenation level-dependent functional MRI at 1.5 T.

Sustained tumor regression of human colorectal cancer xenografts using a multifunctional mannosylated fusion protein in antibody-directed enzyme prodrug therapy.

Purpose: Antibody-directed enzyme prodrug therapy (ADEPT) requires highly selective antibody-mediated delivery of enzyme to tumor. MFE-CP, a multifunctional genetic fusion protein of antibody and enzyme, was designed to achieve this by two mechanisms. First by using a high affinity and high specificity single chain Fv antibody directed to carcinoembryonic antigen.