Prospective tumour mutation burden and neoantigen profiling predicts immunotherapy response in metastatic melanoma
Abstract Tumour mutation burden (TMB) is a promising biomarker in predicting immunotherapy response, yet its reproducibility across target panels needs to be established. This study assessed the reproducibility of TMB estimates in melanoma using TruSight Oncology 500 across two laboratories and compared these results with the FoundationOne CDx and QIAseq TMB IO panels. High concordances in TMB estimation, mutation calls, and BRAF and N/K/HRAS hotspot variants were observed between platforms. In a cohort of 198 pre-treatment biopsies from patients treated with immune checkpoint inhibitors, high TMB (≥10 mut/Mb) was associated with significantly improved response and progression-free survival (PFS), while [...]
Real-world evaluation of the use of melanoma risk prediction tools by clinicians in Australia: a mixed methods study
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A cost comparison of radiotherapy and topical imiquimod for lentigo maligna treatment: Considerations for clinical decision-making
Abstract Background: Lentigo maligna (LM) is an in situ melanoma occurring on sun-damaged skin. Radiotherapy or topical imiquimod are potential alternatives to surgery; a recent randomized trial showed no difference in treatment failure between those approaches (underpowered because of pandemic disruption). Objective: To conduct an economic evaluation comparing radiotherapy versus topical imiquimod for treating LM. Methods: Based on no difference in clinical outcomes, a cost analysis was performed alongside the RADICAL trial, a multi-institutional randomized (1:1) phase 3 study (118/126 patients randomized completed treatment; 60 imiquimod and 58 radiotherapy) conducted in Australia, New Zealand, and Brazil. Direct medical costs and indirect costs [...]
International Dermoscopy Society consensus recommendations for the management of lentigo maligna
Abstract Lentigo maligna (LM) is a subtype of cutaneous melanoma in situ that develops on chronically sun-damaged skin in elderly individuals. Its diagnosis and management remain challenging due to its slow progression, frequent occurrence on cosmetically sensitive areas in frail individuals, and tendency for subclinical peripheral extension. Despite its potential for invasive transformation, the natural history of LM remains incompletely understood and evidence-based management strategies for this specific entity remain limited. This work aims to bridge the gap between scarce high-quality evidence and the clinicians' need for practical guidance on LM management by formulating evidence-based and expert consensus-driven recommendations [...]
The impact of next generation sequencing studies on the diagnosis of BAP1 inactivated melanocytic tumors.
Abstract BAP1 inactivated melanocytic tumors (BIMTs) are recognized for their potential for significant morphologic atypia including nuclear atypia, expansile growth, and mitotic activity, making it difficult to form firm morphologic criteria for malignancy. Next generation sequencing (NGS) is becoming increasingly utilized in melanocytic pathology. We conducted a two-phase survey with 26 dermatopathologists from the International Melanoma Pathology Study Group to assess the impact of NGS on diagnostic accuracy and interobserver agreement in 31 BIMTs. After NGS results, interobserver agreement improved from fair on Survey 1 (κ = 0.348) to moderate on Survey 2 (κ = 0.441). Respondents were 1.7 [...]
Methods to include environmental impacts in a cost-effectiveness analysis: a case study of PET/CT surveillance imaging after treatment for stage III melanoma
Abstract Objectives: To demonstrate methods to include carbon emissions in a cost-effectiveness analysis of different positron emission tomography and computed tomography surveillance imaging schedules for detecting metastasis in patients treated for stage III melanoma. Methods: Decision-analytic modeling was used to compare 12-monthly imaging with no routinely scheduled imaging. The health outcome was the proportion of patients without a false-negative result for a distant metastasis. Health system costs were included in 2023 Australian dollars. A 5% discount per year was applied. Carbon emissions were obtained from existing studies. Four methods were demonstrated: (1) reporting emissions in parallel, (2) the incremental carbon footprint [...]
Prednisolone modulates CD8⁺ and regulatory T-cell activity to dampen response to immune checkpoint inhibitor therapy in melanoma
Abstract Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced melanoma, yet their efficacy is limited by high-grade immune-related adverse events that often require treatment with systemic corticosteroids. Although corticosteroids are widely used, their impact on anti-tumor immunity remains poorly defined. Using an ICI-responsive murine melanoma model, we show that tapered systemic prednisolone administered after three cycles of combined anti-CTLA4 and anti-PD1 therapy compromises ICI-mediated tumor control, leading to delayed progression in one-third of initially responding animals. Mechanistically, prednisolone selectively suppressed CD8+ effector T-cell activation in tumor-draining lymph nodes and in the circulation, while expanding activated regulatory T-cells. These [...]
Global burden of adverse effects of medical treatment from 1990 to 2021: a Global Burden of Disease Study 2021
Abstract Background/aims: This study aims to evaluate the global burden of adverse effects of medical treatment (AEMT) using data from the Global Burden of Disease Study (GBD) 2021. Methods: Data were extracted from the GBD 2021, covering 204 countries/territories from 1990 to 2021. AEMT was defined using ICD-9 and ICD-10 codes, encompassing complications from medical procedures, treatments, or healthcare exposures. Estimates were categorized into fatal and non-fatal outcomes and stratified by age, sex, year, and covariates, including the Socio-demographic Index (SDI). Mortality-incidence ratios (MIRs), defined as the ratio of mortality calculated by dividing the number of deaths by the total incident [...]
The Impact of Next-Generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Deep Penetrating Melanocytic Neoplasms
Abstract Background: Next-generation sequencing (NGS) is becoming more commonly used for diagnosis in dermatopathology. It's critical to appraise its efficacy and limitations. Distinguishing benign deep penetrating nevi (DPN) from deep penetrating like-melanoma (DPN-M) is a challenging diagnostic scenario even for experienced dermatopathologists. Methods: We sent a two-phase survey (pre-and postgenomics) to 32 experienced dermatopathologists to evaluate 39 diagnostically challenging cases from the DPN/WNT-activated family of melanocytic neoplasms. Results: With NGS data, interobserver agreement improved from 0.41 to 0.51 (p < 0.0001) in distinguishing DPN-M from nonmelanoma cases. Overall diagnostic accuracy improved, mostly driven by a 16% increase in accurate diagnosis of DPN-M. [...]
From Analogue to AI: Evolution of Total Body Photography
Abstract Total Body Photography has undergone substantial technological advancement, now embracing high-resolution digital imaging, 3D reconstruction and the potential applications of artificial intelligence (AI), and mobile interoperability. However, its broader implementation is tempered by logistical hurdles as well as concerns regarding cost-effectiveness. This article traces its historical trajectory, evaluates its current clinical utility, and explores future applications. Keywords: AI; TBP; artificial intelligence; melanoma surveillance; total body photography. Read Full Paper