A metabolic pathway for improving adoptive cellular therapy.

In this issue of Cancer Cell, Qiu et al. use single-cell metabolic analysis to identify reduced mannose metabolism as a previously unknown feature of exhausted T cells. This metabolic pathway can be targeted to enhance memory and persistence of adoptively transferred T cells, resulting in improved anti-tumor efficacy.

Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies.

Purpose: To evaluate linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies.

Patients And Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1).

Intra-articular hyaluronic acid and platelet-rich plasma as monotherapy or combination therapy in knee osteoarthritis?

Aim: To systematically identify best current evidence on intra-articular combination therapy with hyaluronic acid (HA) and platelet-rich plasma (PRP), compared to monotherapy in knee osteoarthritis.

Methods: Using the McMaster University and National Health Service five-step systematic approach, we conducted a bottom-up literature search of all existing evidence through Ovid Medline, Ovid Embase, and Cochrane (Central - Wiley) from January 2021 to June 2024.

Results: Of 258 articles retrieved, we systematically narrowed best current evidence to one meta-analysis when evaluating combination therapy versus HA alone.

Profiling current cancer survivorship practices and enhancing survivorship care in public hospitals in Victoria, Australia.

Purpose: Comprehensive survivorship care involves cancer surveillance, management of post-treatment effects, health promotion and coordination between care sectors. This study aimed to understand current survivorship practices, build awareness and support improved survivorship care in Victoria, Australia.

Methods: This project had three components: (1) a survey of 20 Victorian clinical sites, assessing elements described in the Victorian Quality Cancer Survivorship Framework; (2) educational webinars for oncology health professionals, to increase survivorship knowledge and awareness; (3) implementation of targeted survivorship care quality initiatives in a sample of health services.

Neoadjuvant Chemoradiotherapy in Locally Advanced and Locally Recurrent Colon Cancer.

Aims: While systemic management of high risk colon cancer is well addressed, advances in local management remain incremental. This study aims to identify a group of colon cancer patients where local management remains a challenge, and where intensifying local treatment with radiotherapy is potentially beneficial to minimise the risk of an R1 resection.

Materials And Methods: The patients with select cT4 locally advanced primary colon (LAPC) (n = 40) and locally recurrent colon (LRC) (n = 48) adenocarcinomas who received neoadjuvant radiotherapy from 2005 to 2020 were studied.

Surrogate endpoints in mature B-cell neoplasms - meaningful or misleading?

Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting.

Assessment of image quality on the diagnostic performance of clinicians and deep learning models: Cross-sectional comparative reader study.

Background: Skin cancer is a prevalent and clinically significant condition, with early and accurate diagnosis being crucial for improved patient outcomes. Dermoscopy and artificial intelligence (AI) hold promise in enhancing diagnostic accuracy. However, the impact of image quality, particularly high dynamic range (HDR) conversion in smartphone images, on diagnostic performance remains poorly understood.

Protocol for an embedded randomised controlled trial of Early versus Late Stopping of Antibiotics in children with Febrile Neutropenia (ELSA-FN).

In children with cancer, febrile neutropenia (FN) is one of the most common complications of treatment, a leading cause of unplanned and prolonged hospital admission and is the key driver of antibiotic exposure. Co-designed with key stakeholders, 'Early versus Late Stopping of Antibiotics in high-risk FN' (ELSA-FN) is a randomised controlled, non-inferiority trial that compares stopping antibiotics in clinically stable patients after 48 hours with the current standard of care, continuing antibiotics until absolute neutrophil recovery. As an Australian first, we will exploit the potential of electronic medical record (EMR) systems, embedding all key aspects of the trial including screening, consent, randomisation and data collection into standard clinical and EMR workflows.

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Cancer Nursing Frameworks to Guide Clinical Capability, Education and Careers: A Scoping Review of the International Literature.

Aim: This review aimed to provide a current global profile of all existing cancer nursing competency, capability, education and career frameworks and map capabilities and competencies to the clinical, facilitation of education, management and research pillars of practice.

Design: Scoping review.

Data Sources: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Epistemonikos, Google Scholar, Medline, and PubMed.

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes.

The role of the microbiome in immune checkpoint inhibitor colitis and hepatitis.

Immune checkpoint inhibitors have revolutionised management for a variety of different types of malignancies. However, gastrointestinal adverse effects, in particular colitis and hepatitis, are relatively common with up to 30 % of patients being affected. The gut microbiome has emerged as a potential contributor to both the effectiveness of immune checkpoint inhibitors and their side effects.

How often are patients recording their healthcare consultations in Australia and why? An online survey.

Purpose: Recording important healthcare consultations can benefit patients. Technological developments enable recordings by patients and health professionals, as well as real-time 'listening' by AI scribes. Not enough is known about whether and why patients record their consultations.

Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer.

Background And Objective: Advanced prostate cancer (PCa) is enriched for alterations in DNA damage repair genes; poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of drugs that have demonstrated effectiveness in PCa, particularly in tumors with alterations in BRCA1/2 and other homologous recombination repair (HRR) genes, acting through a synthetic lethal mechanism. To prevent or delay drug resistance, and to expand the patient population that can benefit from this class of drug, combination treatment strategies have been developed in preclinical and clinical studies.

Methods: This review examines the latest developments in clinical trials testing PARPi for advanced PCa and their emerging role in earlier disease settings.

Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Purpose: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited.

Methods: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion.

The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably?

Background: Pathologist-read tumor-infiltrating lymphocytes (TILs) have showcased their predictive and prognostic potential for early and metastatic triple-negative breast cancer (TNBC) but it is still subject to variability. Artificial intelligence (AI) is a promising approach toward eliminating variability and objectively automating TILs assessment. However, demonstrating robust analytical and prognostic validity is the key challenge currently preventing their integration into clinical workflows.