LIBELULE: a randomized phase III study to evaluate the clinical relevance of early liquid biopsy in patients with suspicious metastatic lung cancer.

Purpose: Genomic profiling is a major component for first-line treatment decisions in patients with non-small cell lung cancer (NSCLC) and the timeliness of biomarker testing is essential to improve time to treatment initiation (TTI) or avoid inappropriate treatment.

Patients And Methods: The phase III LIBELULE trial (NCT03721120) included patients with radiological suspicion of advanced lung cancer. They were randomized (1:1), the control arm receiving diagnostic procedures according to each center's practice and the liquid biopsy arm with additional testing performed at the first visit using the InVisionFirst®-Lung assay.

Exploring Oesophageal Cancer in Ethiopia: Elevated Incidence in Females and Younger Cases.

Background: Oesophageal cancer is a public health concern in Ethiopia. Identifying the incidence and demographic profile of the two histological subtypes: oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC) are the key steps in recognizing the disease burden and potential aetiopathological associations.

Aim: The aim of this study is to identify the age and gender-specific incidence patterns of the most common subtype of oesophageal cancer in a high-incidence area of Ethiopia.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Multiple mycotoxin exposure assessment through human biomonitoring in an esophageal cancer case-control study in the Arsi-Bale districts of Oromia region of Ethiopia.

Background: Esophageal cancer (EC) is a malignancy with a poor prognosis and a five-year survival rate of less than 20%. It is the ninth most frequent cancer globally and the sixth leading cause of cancer-related deaths. The incidence of EC has been found to vary significantly by geography, indicating the importance of environmental and lifestyle factors along with genetic factors in the onset of the disease.

Using machine learning to predict carotid artery symptoms from CT angiography: A radiomics and deep learning approach.

Purpose: To assess radiomics and deep learning (DL) methods in identifying symptomatic Carotid Artery Disease (CAD) from carotid CT angiography (CTA) images. We further compare the performance of these novel methods to the conventional calcium score.

Methods: Carotid CT angiography (CTA) images from symptomatic patients (ischaemic stroke/transient ischaemic attack within the last 3 months) and asymptomatic patients were analysed.

Large-scale analysis of whole genome sequencing data from formalin-fixed paraffin-embedded cancer specimens demonstrates preservation of clinical utility.

Whole genome sequencing (WGS) provides comprehensive, individualised cancer genomic information. However, routine tumour biopsies are formalin-fixed and paraffin-embedded (FFPE), damaging DNA, historically limiting their use in WGS. Here we analyse FFPE cancer WGS datasets from England's 100,000 Genomes Project, comparing 578 FFPE samples with 11,014 fresh frozen (FF) samples across multiple tumour types.

Bayesian clustering with uncertain data.

Clustering is widely used in bioinformatics and many other fields, with applications from exploratory analysis to prediction. Many types of data have associated uncertainty or measurement error, but this is rarely used to inform the clustering. We present Dirichlet Process Mixtures with Uncertainty (DPMUnc), an extension of a Bayesian nonparametric clustering algorithm which makes use of the uncertainty associated with data points.

Generalisable Overview of Study Risk for Lead Investigators Needing Guidance (GOSLING): A data governance risk tool.

Introduction: Digitisation of patient records, coupled with a moral imperative to use routinely collected data for research, necessitate effective data governance that both facilitates evidence-based research and minimises associated risks. The Generalisable Overview of Study Risk for Lead Investigators Needing Guidance (GOSLING) provides the first quantitative risk-measure for assessing the data-related risks of clinical research projects.

Methods: GOSLING employs a self-assessment designed to standardise risk assessment, considering various domains, including data type, security measures, and public co-production.

Radiology and multi-scale data integration for precision oncology.

In this Perspective paper we explore the potential of integrating radiological imaging with other data types, a critical yet underdeveloped area in comparison to the fusion of other multi-omic data. Radiological images provide a comprehensive, three-dimensional view of cancer, capturing features that would be missed by biopsies or other data modalities. This paper explores the complexities and challenges of incorporating medical imaging into data integration models, in the context of precision oncology.

Second Primary Lung Cancer - An Emerging Issue in Lung Cancer Survivors.

As a result of an increased focus on early detection including lung cancer screening, combined with more curative treatment options, the 5-year survival rates for lung cancer are improving. Welcome though this is, it brings new, hitherto unseen challenges. As more patients are cured and survive longer, they are at risk of developing second primary cancers, particularly lung cancer.

Mitigating the impact of image processing variations on tumour [F]-FDG-PET radiomic feature robustness.

Radiomics analysis of [F]-fluorodeoxyglucose ([F]-FDG) PET images could be leveraged for personalised cancer medicine. However, the inherent sensitivity of radiomic features to intensity discretisation and voxel interpolation complicates its clinical translation. In this work, we evaluated the robustness of tumour [F]-FDG-PET radiomic features to 174 different variations in intensity resolution or voxel size, and determined whether implementing parameter range conditions or dependency corrections could improve their robustness.

Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment.

Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase.

Lenvatinib plus pembrolizumab for patients with previously treated advanced ovarian cancer: Results from the phase 2 multicohort LEAP-005 study.

Objectives: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort.

Methods: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy.

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.

Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers.

With the foundation pre-laid, research in the new millennium has readily excavated and expanded upon the architectural framework laid out by Otto Warburg's seminal work in a new wave of "westward expansion," ever widening our understanding of cancer metabolism beyond the telescopic vision seen over a century ago. On this path, the unique circuitry of the cancer metabolic program has been elucidated, illuminating mutations of conserved cellular pathways implicated in tumorigenesis. Paramount among these are mutations in tricarboxylic acid cycle enzymes, succinate dehydrogenase, and fumarate hydratase, leading to deleterious accumulations in metabolic intermediates, "oncometabolites," the pilots of the disease process.

Patient experiences of Cytosponge: a qualitative study.

Objective: Cytosponge is a novel technology for oesophageal pathology diagnosis. Uses include diagnosis of Barrett's oesophagus and as a triage tool to prioritise upper gastrointestinal endoscopy. Patient experience is a key component of quality care.

Genomic evolution shapes prostate cancer disease type.

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types.

Dementia risk factors in former contact sports participants: prospective cohort study.

Background: The elevated dementia incidence in retired contact sport participants might be explained by a higher prevalence of established risk factors for the disease relative to the general population.

Methods: In this cohort study, former elite participants active between 1920 and 1965 in soccer (N=303), boxing (N=281), and wrestling (N=318) were recruited using sports yearbooks and records of sports associations. Men in a population control group were identified using records from a compulsory medical examination (N=1712).

Mapping inherited genetic variation with opposite effects on autoimmune disease and cancer identifies candidate drug targets associated with the anti-tumor immune response.

Background: Germline alleles near genes that encode certain immune checkpoints () are associated with autoimmune/autoinflammatory disease and cancer but in opposite directions. This motivates a systematic search for additional germline alleles which demonstrate this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetic evidence.

Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with follow-up.

Quo Vadis Hyperpolarized C MRI?

Over the last two decades, hyperpolarized C MRI has gained significance in both preclinical and clinical studies, hereby relying on technologies like PHIP-SAH (ParaHydrogen-Induced Polarization-Side Arm Hydrogenation), SABRE (Signal Amplification by Reversible Exchange), and dDNP (dissolution Dynamic Nuclear Polarization), with dDNP being applied in humans. A clinical dDNP polarizer has enabled studies across 24 sites, despite challenges like high cost and slow polarization. Parahydrogen-based techniques like SABRE and PHIP offer faster, more cost-efficient alternatives but require molecule-specific optimization.