The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.

A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling.

Background: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

Methods: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type.

The value of real world evidence and pragmatic trials in advanced prostate cancer- insights from the electronic Prostate Cancer Australian and Asian Database.

Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population.

Oral Etoposide for Relapsed or Refractory Ewing Sarcoma in Adolescent and Adult Patients.

Prognosis remains poor for patients with relapsed or refractory Ewing sarcoma, with limited treatment options after first-line therapy. Oral etoposide has efficacy in the paediatric setting; however, data are limited in adults. A retrospective analysis was conducted on 33 patients with relapsed or refractory Ewing sarcoma who completed at least one cycle of oral etoposide at the Peter MacCallum Cancer Centre from 2005 to 2020.

Phase II randomized study of dostarlimab alone or with bevacizumab versus non-platinum chemotherapy in recurrent gynecological clear cell carcinoma (DOVE/APGOT-OV7/ENGOT-ov80).

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach.

Analysis of risk factors for immune-related adverse events induced by immune checkpoint inhibitor treatment in cancer: a comprehensive systematic review.

Background: Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rarer irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach.

Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm.

Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small-molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post-MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine.

Evaluating the impact of a tertiary multidisciplinary meeting in metastatic breast cancer: A prospective study.

Background: Metastatic breast cancer (mBC) guidelines recommend multidisciplinary meetings (MDM), but there is limited research on their impact. This prospective study examines the impact of an mBC MDM on management plans, their implementation rate, and costs and benefits at an Australian metropolitan breast cancer center.

Methods: Consecutive mBC MDM patients were enrolled.

Hormone-responsive progenitors have a unique identity and exhibit high motility during mammary morphogenesis.

Hormone-receptor-positive (HR) luminal cells largely mediate the response to estrogen and progesterone during mammary gland morphogenesis. However, there remains a lack of consensus on the precise nature of the precursor cells that maintain this essential HR lineage. Here we refine the identification of HR progenitors and demonstrate their unique regenerative capacity compared to mature HR cells.

Demographics and Health Characteristics Associated With the Likelihood of Participating in Digitally Delivered Exercise Rehabilitation for Improving Heart Health Among Breast Cancer Survivors: Cross-Sectional Survey Study.

Background: Strong evidence supports the benefits of exercise following both cardiovascular disease and cancer diagnoses. However, less than one-third of Australians who are referred to exercise rehabilitation complete a program following a cardiac diagnosis. Technological advances make it increasingly possible to embed real-time supervision, tailored exercise prescription, behavior change, and social support into home-based programs.

Lung function may recover after coal mine fire smoke exposure: a longitudinal cohort study.

Background And Objective: The 2014 Hazelwood coal mine fire exposed residents in nearby Morwell to high concentrations of particulate matter <2.5 µm (PM) for approximately 6 weeks. This analysis aimed to evaluate the long-term impact on respiratory health.

Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision.

Single-nucleotide variants (SNVs) are extremely prevalent in human cancers, although most of these remain clinically unactionable. The programmable RNA nuclease CRISPR-Cas13 has been deployed to specifically target oncogenic RNAs. However, silencing oncogenic SNVs with single-base precision remains extremely challenging due to the intrinsic mismatch tolerance of Cas13.

Management, outcomes and predictors of mortality of Cryptococcus infection in patients without HIV: a multicentre study in 46 hospitals from Australia and New Zealand.

Background: Limited data exist regarding outcomes of cryptococcosis in patients without HIV with few studies having compared outcomes of Cryptococcus gattii, versus C. neoformans, infection.

Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019, and compared outcomes of C.

Glucocorticoid dosing and implications for vaccination: Evolution of global definitions.

Despite widespread adoption of "high-dose" glucocorticoid definitions across international immunisation guidelines (i.e., prednisone-equivalent dosing >20 mg/day, or >2 mg/kg/day in children), the rationale remains unclear.

Stereotactic ablative radiotherapy for primary kidney cancer - An international patterns of practice survey.

Purpose: To conduct an international survey of radiation oncologists treating primary renal cell carcinoma (RCC) with SABR to ascertain the general patterns of SABR use, common dose/treatment/follow-up details, and expected outcomes.

Materials And Methods: A 51-question survey was created containing the following themes: prevalence and clinical scenarios in which RCC SABR is used, dose-fractionation schedules, treatment delivery details, follow-up/outcome assessments, and implementation barriers. The survey was distributed widely across multiple influential radiation oncology societies and social media, and ran from January to April 2023.

The Impact of Synchrotron Microbeam Radiation Therapy Combined With Broad Beam in a Preclinical Breast Cancer Model.

Purpose: Both local tumor control and distant metastasis are important indicators of the efficacy of radiation therapy treatment. Synchrotron microbeam radiation therapy (MRT), spatially fractionated radiation delivered at ultrahigh dose rates, shows remarkable normal tissue sparing with excellent local control in some models. Some MRT regimens trigger an antitumor immune response that contributes not only to the local but also to systemic treatment efficacy.

Short-Term Effectiveness of a Stepped-Care Model to Address Fear of Cancer Recurrence in Patients With Early-Stage Melanoma.

Objective: To investigate the effectiveness of the Melanoma Care Programme when implemented into routine clinical practice coupled with fear of cancer recurrence (FCR) screening and a stepped-care model of intervention delivery.

Methods: Using a Type-I hybrid effectiveness-implementation design, individuals with stage 0-II melanoma and a Fear of Cancer Recurrence Inventory FCR severity score of ≥ 13 were offered the Melanoma Care Programme. The programme included a psychoeducational booklet and 3 to 5 psychotherapeutic telehealth sessions with a clinical psychologist, timed around routine dermatological appointments.

Geospatial analyses demonstrate variation of cutaneous T-cell lymphomas across Australia, providing insights into possible causes.

Background: Cutaneous T-cell lymphomas (CTCL) are rare with distinct diagnostic challenges. Equitable access to cancer care is a recognised priority, internationally. To date, the geospatial distribution of CTCL has not been definitively studied.

Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk.

Menopausal hormone therapy (MHT) users are at increased breast cancer (BC) risk and decreased colorectal cancer (CRC) risk compared with never users, but these opposing associations might differ by familial risk of BC and CRC. We harmonized data from three cohorts and generated separate BC and CRC familial risk scores (FRS) based on cancer family history. We defined moderate/strong family history as FRS ≥ 0.

Artificial intelligence improves mammography-based breast cancer risk prediction.

Artificial intelligence (AI) is enabling us to delve deeply into the information inherent in a mammogram and identify novel features associated with high risk of a future breast cancer diagnosis. Here, we discuss how AI is improving mammographic density-associated risk prediction and shaping the future of screening and risk-reducing strategies.

Breaking Down the Barriers for Patients With Cutaneous T-Cell Lymphoma: Current Controversies and Challenges for Radiation Oncologists in 2024.

Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological diagnoses and for collaborative therapeutic decisions throughout the management journey, which frequently involves multiple lines of therapy. Radiotherapy (RT) is a highly effective skin-directed therapy for CTCL, commonly delivered as localised fields or as total skin electron beam therapy (TSEBT).

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).