Prophylaxis for renal patients at risk of COVID-19 infection: results from the intranasal niclosamide randomised, double blinded, placebo controlled arm of the PROTECT-V platform trial.

Purpose: Despite vaccination, many patients remain vulnerable to COVID-19 infection and poorer outcomes, because of underlying health conditions resulting in sub-optimal vaccine responses. This study aims to demonstrate whether intranasal niclosamide confers additional protection against COVID-19 infection above standard preventative measures including vaccination.

Methods: PROTECT-V (PROphylaxis for paTiEnts at risk of COVID-19 infecTion) is a platform trial testing multiple pre-exposure COVID-19 prophylactic agents in vulnerable patients.

Quality of life in advanced-stage, asymptomatic, non-bulky follicular lymphoma treated with rituximab shows significant improvement compared with watchful-waiting.

Traditionally, patients with asymptomatic, advanced-stage follicular lymphoma were managed with a watchful-waiting approach until disease progression. The 'Watch and Wait' Phase-3 randomised international trial examined whether rituximab could delay the need for treatment and the effect on quality of life (QoL). In this article, we present the long-term results of the QoL aspect of the trial.

A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of Rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING).

Background: Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50-60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use.

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer, who were germline BRCA1 and BRCA2 wild type. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAF mutant advanced melanoma (INTERIM).

Background: BRAF+MEK inhibitors extend life expectancy of patients with BRAF mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen.

Refining the Intraoperative Identification of Suspected High-Grade Glioma Using a Surgical Fluorescence Biomarker: GALA BIDD Study Report.

Background: Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling.

Methods: We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery.

Results: A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled.

Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

Purpose: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI.

Method: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT.

Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib.

Objective: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial.

Patients And Methods: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50 mg once daily sunitinib for 12 days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12 days.

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource.

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn's disease (CD), including their impact on need for surgery.

Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission.

Trajectories of Haemoglobin and incident stroke risk: a longitudinal cohort study.

Background: Studies have demonstrated that high or low haemoglobin increases the risk of stroke. Previous studies, however, performed only a limited number of haemoglobin measurements, while there are dynamic haemoglobin changes over the course of a lifetime. This longitudinal cohort study aimed to classify the long-term trajectory of haemoglobin and examine its association with stroke incidence.

Routine preoperative brain CT in resectable non-small cell lung cancer - Ten years experience from a tertiary UK thoracic center.

Objectives: Although detection of brain metastasis can change treatment intent in non-small cell lung carcinoma (NSCLC), head imaging is not routinely performed during initial staging. In our previous study, 4.8% of patients considered for surgical treatment had asymptomatic synchronous brain metastases, encouraging us to include contrast-enhanced head CT (CE-CT) in our routine staging protocol.

Local alkylating chemotherapy applied immediately after 5-ALA guided resection of glioblastoma does not provide additional benefit.

Grade IV glioma is the most common and aggressive primary brain tumour. Gross total resection with 5-aminolevulinic acid (5-ALA) guided surgery combined with local chemotherapy (carmustine wafers) is an attractive treatment strategy in these patients. No previous studies have examined the benefit carmustine wafers in a treatment programme of 5-ALA guided resection followed by a temozolomide-based chemoradiotherapy protocol.

Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial.

Background: The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment.

Methods: Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

Background: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP).

A Comparison of Outcomes Following Laparoscopic and Open Hysterectomy With or Without Lymphadenectomy for Presumed Early-Stage Endometrial Cancer: Results From the Medical Research Council ASTEC Trial.

Objectives: Laparoscopic hysterectomy (LH) is increasingly used for the management of endometrial malignancy. Its benefits may be particularly pronounced as these women are more likely to be older or obese. The aim of this study was to determine whether outcomes for LH are comparable to the open hysterectomy (OH).

Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients.

Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet.

Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: results from the Cambridge Breast IMRT trial.

Background: The use of intensity-modulated radiotherapy (IMRT) in breast cancer reduces clinician-assessed breast tissue toxicity including fibrosis, telangectasia and sub-optimal cosmesis. Patient reported outcome measures (PROMs) are also important as they provide the patient's perspective. This longitudinal study reports on (a) the effect of forward planned field-in-field IMRT (∼simple IMRT) on PROMs compared to standard RT at 5 years after RT, (b) factors affecting PROMs at 5years after RT and (c) the trend of PROMs over 5 years of follow up.

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer.

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis.

Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours.

Background: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin.

Methods: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.