Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial.

Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.

Patients And Methods: Phase II trial with two entry points (EP1, EP2).

A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS).

Objectives: Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc.

A randomised, pragmatic clinical trial of ACUpuncture plus standard care versus standard care alone FOr Chemotherapy Induced peripheral Neuropathy (ACUFOCIN).

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity posing a major clinical challenge for managing patients receiving specific chemotherapy regimens (e.g., Taxanes).

A multi-modality medical imaging head and neck phantom: Part 2. Medical imaging.

The head and neck phantom discussed in an accompanying paper (part 1), is imaged with MRI, X-ray CT, PET and ultrasound. MRI scans show a distinct image contrast between the brain compartment and other anatomical regions of the head. The silicone matrix that was used to create a porous brain compartment has a relatively high proton density and a spin-spin relaxation time (T) that is long enough to provide an MRI signal.

A multi-modality medical imaging head and neck phantom: Part 1. Design and fabrication.

A novel anthropomorphic head and neck phantom which features the emulation of blood flow and perfusion is proposed. The phantom is helpful in both education and research and contains major blood vessels and a porous silicone elastomer brain compartment with microvascular capillary flow. The porous brain compartment is fabricated by use of a novel cast-moulding-dissolution technique.

Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis (PRedSS).

Background: Many of the painful, disabling features of early diffuse cutaneous systemic sclerosis have an inflammatory component and are potentially treatable with corticosteroid therapy. These features include painful and itchy skin, fatigue and musculoskeletal involvement. Yet many clinicians are understandably reluctant to prescribe corticosteroids because of the concern that these are a risk factor for scleroderma renal crisis.

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.

Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer.

Background: The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response. Selumetinib inhibits MEK and enhances effects of radiotherapy in preclinical studies.

Patients And Methods: Single-arm, single-centre, open-label phase I trial.

Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study.

Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification.

A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08).

Background: Cisplatin/gemcitabine is standard first-line treatment for patients with advanced biliary tract cancer (ABC). NUC-1031 (phosphoramidate transformation of gemcitabine) is designed to enhance efficacy by maximizing intratumoral active metabolites.

Methods: Patients with untreated ABC, Eastern Cooperative Oncology Group performance status 0-1 received NUC-1031 (625 or 725 mg/m ) and cisplatin (25 mg/m ) on days 1 and 8, every 21 days.

Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial.

Purpose: Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM.

Methods: After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy.

Translocator protein localises to CD11b macrophages in atherosclerosis.

Background And Aims: Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease.

PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial.

Purpose: Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth . Presurgical window studies allow rapid assessment of antitumor activity.

Direct Estimation of Voxel-Wise Neurotransmitter Response Maps From Dynamic PET Data.

Computational methods, such as the linear parametric neurotransmitter PET (lp-ntPET) method, have been developed to characterize the transient changes in radiotracer kinetics in the target tissue during endogenous neurotransmitter release. In this paper, we describe and evaluate a parametric reconstruction algorithm that uses an expectation maximization framework, along with the lp-ntPET model, to estimate the endogenous neurotransmitter response to stimuli directly from the measured PET data. Computer simulations showed that the proposed direct reconstruction method offers improved accuracy and precision for the estimated timing parameters of the neurotransmitter response at the voxel level ( t=1±2 min, for activation onset bias and standard deviation) compared with conventional post reconstruction modeling ( t=4±7 min).

Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals.

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals.

White matter integrity alterations in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma-exposed age- and gender-matched controls. Participants underwent clinical assessment and magnetic resonance imaging.

Frontal and subcortical grey matter reductions in PTSD.

Post-traumatic stress disorder (PTSD) is characterised by a range of debilitating psychological, physical and cognitive symptoms. PTSD has been associated with grey matter atrophy in limbic and frontal cortical brain regions. However, previous studies have reported heterogeneous findings, with grey matter changes observed beyond limbic/frontal areas.

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT.

This paper describes the use of F-FDG and micro-PET/CT imaging to determine in vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired uptake and metabolism of glucose in multiple organ systems due to insulin resistance is a hallmark of type 2 diabetes. The ability of this technique to extract an image-derived input function from the vena cava using an iterative deconvolution method eliminates the requirement of the collection of arterial blood samples.

Rigid motion correction of dual opposed planar projections in single photon imaging.

Awake and/or freely moving small animal single photon emission imaging allows the continuous study of molecules exhibiting slow kinetics without the need to restrain or anaesthetise the animals. Estimating motion free projections in freely moving small animal planar imaging can be considered as a limited angle tomography problem, except that we wish to estimate the 2D planar projections rather than the 3D volume, where the angular sampling in all three axes depends on the rotational motion of the animal. In this study, we hypothesise that the motion corrected planar projections estimated by reconstructing an estimate of the 3D volume using an iterative motion compensating reconstruction algorithm and integrating it along the projection path, will closely match the true, motion-less, planar distribution regardless of the object motion.

iCAP: An Individualized Model Combining Gaze Parameters and Image-Based Features to Predict Radiologists' Decisions While Reading Mammograms.

This study introduces an individualized tool for identifying mammogram interpretation errors, called eye-Computer Assisted Perception (iCAP). iCAP consists of two modules, one which processes areas marked by radiologists as suspicious for cancer and classifies these as False Positive (FP) or True Positive (TP) decisions, while the second module classifies fixated but not marked locations as False Negative (FN) or True-Negative (TN) decisions. iCAP relies on both radiologists' gaze-related parameters, extracted from eye tracking data, and image-based features.

Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism.

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice).