Tumour Mutational Burden and Immune Checkpoint Inhibitor Response in Non-small Cell Lung Cancer: A Continuous Modelling Approach.

Background: Tumour mutational burden (TMB) is an established biomarker for patients treated with immune checkpoint inhibitors (ICIs). The optimal TMB cut-off is uncertain. It is also uncertain whether there is a sharp TMB threshold or a more graduated change in clinical outcomes as TMB increases.

Hypothalamic-Pituitary-Adrenal Axis Dysfunction in People With Cancer: A Systematic Review.

Purpose: Cancer can be a source of significant psychological and physical stress. Prolonged stressful stimuli can influence the stress response, mediated by the hypothalamic-pituitary-adrenal (HPA) axis. However, there is limited literature investigating HPA axis function in patients with cancer.

Anorexia nervosa polygenic risk, beyond diagnoses: relationship with adolescent disordered eating and behaviors in an Australian female twin population.

Background: It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure.

Feasibility, acceptability, and preliminary efficacy of a self-directed online psychosocial intervention for women with metastatic breast cancer: Finding My Way-Advanced.

Purpose: Few digital interventions target patients with advanced cancer. Hence, we feasibility-tested Finding My Way-Advanced (FMW-A), a self-guided program for women with metastatic breast cancer.

Methods: A single-site randomised controlled pilot trial was conducted.

Utilisation of Medicare chronic disease management item numbers for people with cancer in Queensland, Australia.

Objective Chronic disease is common in people with cancer. However, the utilisation of Medicare chronic disease management (CDM) items for cancer patients in Australia remains unexplored. This study investigates Medicare CDM item numbers relating to people with cancer, including general practitioner (GP) and allied health CDM item numbers, and any associated sociodemographic factors.

Adequate assessment yields appropriate care-the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group.

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment decisions, and follow-up, as well as informing supportive care interventions. Geriatric assessment and management (GAM) refers to the comprehensive evaluation of an older individual's health status with subsequent management plans focusing on both oncologic and non-oncologic interventions.

New developments in AMPK and mTORC1 cross-talk.

Metabolic homeostasis and the ability to link energy supply to demand are essential requirements for all living cells to grow and proliferate. Key to metabolic homeostasis in all eukaryotes are AMPK and mTORC1, two kinases that sense nutrient levels and function as counteracting regulators of catabolism (AMPK) and anabolism (mTORC1) to control cell survival, growth and proliferation. Discoveries beginning in the early 2000s revealed that AMPK and mTORC1 communicate, or cross-talk, through direct and indirect phosphorylation events to regulate the activities of each other and their shared protein substrate ULK1, the master initiator of autophagy, thereby allowing cellular metabolism to rapidly adapt to energy and nutritional state.

Restricting Colorectal Cancer Cell Metabolism with Metformin: An Integrated Transcriptomics Study.

Background: Metformin is a first-line therapy for type 2 diabetes as it disrupts cellular metabolism. Despite the association between metformin and lower cancer incidence, the anti-tumour activity of the drug in colorectal cancer (CRC) is incompletely understood. This study identifies underlying molecular mechanisms by which metformin slows colorectal cancer cell proliferation by investigating metformin-associated microRNA (miRNA) and target gene pairs implicated in signalling pathways.

Cancer survivor preferences for breast cancer follow-up care: a discrete choice experiment.

Purpose: To identify the key attributes of breast cancer follow-up care models preferred by cancer survivors in Australia.

Methods: A discrete choice experiment (DCE) was conducted to elicit preferences for attributes of breast cancer follow-up care. Respondents were presented with two hypothetical scenarios, known as choice sets, and asked to select a preference.

Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors.

Background: Studies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors.

Current safeguards, risk mitigation, and transparency measures of large language models against the generation of health disinformation: repeated cross sectional analysis.

Objectives: To evaluate the effectiveness of safeguards to prevent large language models (LLMs) from being misused to generate health disinformation, and to evaluate the transparency of artificial intelligence (AI) developers regarding their risk mitigation processes against observed vulnerabilities.

Design: Repeated cross sectional analysis.

Setting: Publicly accessible LLMs.

Medication-based Comorbidity Measures and Prostate Cancer Treatment Selection.

Introduction: We aimed to assess the association between comorbidities and prostate cancer management.

Patients And Methods: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk).

A 10-year update to the principles for clinical trial data sharing by pharmaceutical companies: perspectives based on a decade of literature and policies.

Data sharing is essential for promoting scientific discoveries and informed decision-making in clinical practice. In 2013, PhRMA/EFPIA recognised the importance of data sharing and supported initiatives to enhance clinical trial data transparency and promote scientific advancements. However, despite these commitments, recent investigations indicate significant scope for improvements in data sharing by the pharmaceutical industry.

Heterogeneity and Utility of Pharmaceutical Company Sharing of Individual-Participant Data Packages.

Importance: The pharmaceutical industry has made substantial investments in developing processes for sharing individual-participant data (IPD) from clinical trials. However, the utility and completeness of shared IPD and supporting documents must be evaluated to ensure the potential for scientific advancements from the data sharing ecosystem can be realized.

Objective: To assess the utility and completeness of IPD and supporting documents provided from industry-sponsored clinical trials.

Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer.

Background: Family history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited.

Aims: To assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC.

Geriatric assessment for older people with cancer: policy recommendations.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers.

Dodecafluoropentane Emulsion as a Radiosensitizer in Glioblastoma Multiforme.

Purpose: Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM.

Experimental Design: In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.