Menzies, Alex

Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside.

Abstract Immune checkpoint inhibitors have transformed the landscape of oncological therapy, but at the price of a new array of immune related adverse events. Among these is β-cell failure, leading to checkpoint inhibitor-related autoimmune diabetes (CIADM) which entails substantial long-term morbidity. As our understanding of this novel disease grows, parallels and differences between CIADM and classic type 1 diabetes (T1D) may provide insights into the development of diabetes and identify novel potential therapeutic strategies. In this review, we outline the knowledge across the disciplines of endocrinology, oncology and immunology regarding the pathogenesis of CIADM and identify possible management strategies. [...]

November 5th, 2021|Comments Off on Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside.

Association Between Melanoma Detected During Routine Skin Checks and Mortality.

Abstract Importance: Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality. Objective: To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection. Design, setting, and participants: This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study [...]

November 3rd, 2021|Comments Off on Association Between Melanoma Detected During Routine Skin Checks and Mortality.

Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition – A Descriptive Observational Retrospective Multicenter Analysis.

Abstract Introduction: Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods: This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, [...]

October 21st, 2021|Comments Off on Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition – A Descriptive Observational Retrospective Multicenter Analysis.

Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Abstract Background: Immune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis. Methods: In this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We [...]

October 11th, 2021|Comments Off on Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy.

Abstract Background: Immune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients. Methods: Institutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab. Results: Twenty-two patients were identified. Two were [...]

September 15th, 2021|Comments Off on Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy.

Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews.

Abstract Background: Adjuvant immunotherapy is revolutionising care for patients with resected stage III and IV melanoma. However, immunotherapy may be associated with toxicity, making treatment decisions complicated. This study aimed to identify factors physicians and nurses considered regarding adjuvant immunotherapy for melanoma. Methods: In-depth interviews were conducted with physicians (medical oncologists, surgeons and dermatologists) and nurses managing patients with resected stage III melanoma at three Australian tertiary melanoma centres between July 2019 and March 2020. Factors considered regarding adjuvant immunotherapy were explored. Recruitment continued until data saturation and thematic analysis was undertaken. Results: Twenty-five physicians and nurses, aged 28-68 years, 60% females, [...]

September 10th, 2021|Comments Off on Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews.

Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis.

Abstract Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBASE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan-Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa [...]

August 23rd, 2021|Comments Off on Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis.

Early use of high-dose-glucocorticoid for the management of irAE is associated with poorer survival in patients with advanced melanoma treated with anti-PD-1 monotherapy

Abstract Purpose: Programmed cell death receptor-1 (PD-1) inhibitors are frontline therapy in advanced melanoma. Severe immune-related adverse effects (irAEs) often require immunosuppressive treatment with glucocorticoids (GCCs), but GCC use and its correlation with patient survival outcomes during anti-PD-1 monotherapy remains unclear. Experimental design: In this multicenter retrospective analysis, patients treated with anti-PD-1 monotherapy between 2009 and 2019 and detailed GCC use, data were identified from five independent cohorts, with median follow-up time of 206 weeks. IrAEs were tracked from the initiation of anti-PD-1 until disease progression, initiation of a new therapy, or last follow-up. Correlations between irAEs, GCC use, and survival [...]

August 10th, 2021|Comments Off on Early use of high-dose-glucocorticoid for the management of irAE is associated with poorer survival in patients with advanced melanoma treated with anti-PD-1 monotherapy

Survival Outcomes of Salvage Metastasectomy after Failure of Modern-Era Systemic Therapy for Melanoma

Abstract Background: Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy. Methods: Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic therapy was [...]

August 10th, 2021|Comments Off on Survival Outcomes of Salvage Metastasectomy after Failure of Modern-Era Systemic Therapy for Melanoma
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