Publications by authors named "Loi S"

Purpose: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.

Methods: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.

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Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

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Introduction: In this review, we evaluate the role of stromal tumor-infiltrating lymphocytes (sTILs) as a biomarker in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, exploring the prognostic and predictive potential in various treatment settings.

Methods: Data from multiple clinical trials in the early and metastatic settings, focusing on TILs' correlation with pathologic complete response (pCR), progression-free survival (PFS), and overall survival across early and metastatic HER2-positive breast cancer were summarized. This review also discusses TILs' assessment methods, interobserver variability, and emerging technologies to assess TILs.

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Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.

Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease ( = 18), non-Alzheimer's disease neurodegeneration ( = 23) or primary psychiatric disorders ( = 24).

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Triple negative breast cancers often contain higher numbers of tumour-infiltrating lymphocytes compared with other breast cancer subtypes, with their number correlating with prolonged survival. Since little is known about tumour-infiltrating lymphocyte trafficking in triple negative breast cancers, we investigated the relationship between tumour-infiltrating lymphocytes and the vascular compartment to better understand the immune tumour microenvironment in this aggressive cancer type. We aimed to identify mechanisms and signaling pathways responsible for immune cell trafficking in triple negative breast cancers, specifically of basal type, that could potentially be manipulated to change such tumours from immune "cold" to "hot" thereby increasing the likelihood of successful immunotherapy in this challenging patient population.

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Background: The rise of Artificial intelligence (AI) is reshaping healthcare, particularly in medical imaging. In this emerging field, clinical imaging personnel need proper training. However, formal AI education is lacking in medical curricula, coupled with a shortage of studies synthesising the availability of AI curricula tailored for clinical imaging personnel.

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Objective: We investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), and neurofilament light (NfL) to distinguish biomarker-defined Alzheimer disease (AD) from non-AD conditions, in a heterogenous clinical cohort of younger people.

Methods: Plasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other CSF profiles (Other).

Results: Seventy-nine patients were included, median age 60.

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Article Synopsis
  • A modified e-Delphi study was conducted with Australian clinical experts to establish minimum and gold standard assessments for young-onset dementia (YOD), using 72 statements adapted from a previous international study.
  • Experts rated the statements on a scale of 1-7, with consensus determined by the percentage of respondents who found specific statements essential or important.
  • The study achieved full consensus on 13 statements (minimum standard) and high consensus on 37 statements (gold standard), highlighting the importance of family history and routine tests in diagnosing YOD, while noting differences from previous findings in the international study.
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In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial (NCT00490139), we identify and characterize five molecular subtypes associated with the risk of distant recurrence: immune-enriched, proliferative/metabolic-enriched, mesenchymal/stroma-enriched, luminal, and ERBB2-dependent.

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Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

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  • * In a phase 3 trial involving 325 patients, those taking inavolisib had a median progression-free survival of 15.0 months, significantly better than the 7.3 months for the placebo group, indicating better disease management.
  • * The treatment with inavolisib showed promising results with a 58.4% objective response rate; however, there were notable side effects, similar between both groups, including high rates of neutropenia
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  • The NATALEE trial evaluated the effectiveness of ribociclib in combination with nonsteroidal aromatase inhibitors (NSAI) compared to NSAI alone over three years for treating HR+/HER2- early breast cancer patients.
  • The study involved 5,101 patients who were randomized to receive either ribociclib plus NSAI or NSAI alone, with the primary focus on invasive disease-free survival (iDFS).
  • Results showed that ribociclib plus NSAI significantly improved iDFS, with 90.7% of patients remaining disease-free compared to 87.6% for those on NSAI alone, while safety profiles remained consistent with no new safety concerns.
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The role of adaptive immunity in long-term outcomes in early breast cancer is increasingly recognised. Standard (neo)adjuvant chemotherapy can have adverse effects on immune cells. We conducted a retrospective longitudinal study of full blood counts (FBC) of 200 patients receiving (neo)adjuvant chemotherapy for early breast cancer at a single institution.

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  • People with neurodegenerative disorders often experience delays and misdiagnosis, making it important to find effective diagnostic tools.
  • This study compared levels of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) among individuals with neurodegenerative disorders (ND), primary psychiatric disorders (PPD), and healthy controls, showing that plasma NfL was significantly elevated in ND.
  • The research indicates that plasma NfL has strong diagnostic performance, especially in younger individuals, suggesting it could serve as a useful screening test to differentiate between ND and PPD in clinical settings.
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  • The study investigated the prevalence and types of young onset dementia (YOD) in New South Wales, Australia, in 1891, comparing it to 21st-century data to aid future healthcare planning.
  • A total of 161 potential dementia cases were reviewed, with 123 diagnosed as 'probable' dementia, primarily affecting males, and the most common type being 'unspecified dementia.'
  • Key clinical symptoms included neurological signs, psychosis, and agitation, with a significant number of cases either dying in the hospital or being transferred to long-term care facilities.
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Introduction: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain.

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  • The phase 3 KEYNOTE-355 study showed that pembrolizumab combined with chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) in patients with untreated, advanced triple-negative breast cancer and high PD-L1 levels compared to placebo with chemotherapy.
  • Approximately 64% of patients enrolled in Asian countries, such as Hong Kong, Japan, and Malaysia, had tumors with a PD-L1 combined positive score of 1 or higher, with 35% having a score of 10 or higher.
  • Treatment with pembrolizumab plus chemotherapy resulted in manageable side effects, with similar rates of grade 3/4 adverse events compared to the placebo group, indicating a favorable benefit-risk profile.
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Objectives: The primary aim of this pragmatic stepped-wedge cluster RCT was to determine the efficacy of a co-designed dementia specialist training program (the PITCH program) for home care workers (HCWs) to improve their confidence and knowledge when providing care for clients living with dementia.

Methods: HCWs who provided care to clients with dementia were recruited from seven home care service provider organisations in Australia between July 2019 and May 2022, and randomised into one of 18 clusters. The primary outcome was HCW's sense of self-competence in providing care services to people living with dementia at 6 months post PITCH training measured by the Sense of Competence in Dementia Care Staff (SCIDS) Scale.

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Using population-level cancer diagnosis data, we compared cancer incidence in locations affected by smoke from a six week-long open cut coal mine fire in regional Victoria, Australia, up to seven years following the event. There was no detectable effect on cancer incidence overall. While several subgroups exhibited changes, these were more likely due to statistical chance rather than real effects.

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Objective: Women face considerable barriers in pursuing careers in academic psychiatry.

Methods: A group of Australian and New Zealand academic women psychiatrists convened in September 2022 to identify and propose solutions to increase opportunities for women in academic psychiatry.

Results: Limiting factors were identified in pathways to academia including financial support, engagement and coordination between academia and clinical services, and flexible working conditions.

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  • The study investigates how stromal tumor-infiltrating lymphocytes (sTILs) relate to survival in patients with metastatic breast cancer (MBC).
  • The research showed that sTILs positively impacted progression-free survival in those receiving chemotherapy, but this link weakened after accounting for hormone receptor status.
  • The trial involved is CALGB 40502, which has since become part of the Alliance for Clinical Trials in Oncology and is registered on ClinicalTrials.gov.
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Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

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