Factors influencing acceptance, adoption and adherence to sentinel node biopsy recommendations in the Australian Melanoma Management Guidelines: a qualitative study using an implementation science framework.
Abstract Background: Sentinel node biopsy (SN biopsy) is a surgical procedure used to accurately stage patients with primary melanoma at high risk of recurrence. Although Australian Melanoma Management Guidelines recommend SN biopsy be considered in patients with melanomas > 1 mm thick, SN biopsy rates in Australia are reportedly low. Our objective was to identify factors impacting the acceptance, adoption and adherence to the Australian SN biopsy guideline recommendations. Methods: Opinions of Australian key informants including clinicians, representatives from melanoma education and training providers, professional associations and colleges, and melanoma advocacy organisations were collected through semi-structured interviews (n = [...]
Comparative genomics provides etiological and biological insights into melanoma subtypes
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 [...]
Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites.
Abstract Background: The liver is a known site of resistance to immunotherapy and the presence of liver metastases is associated with shorter progression-free and overall survival (OS) in melanoma, while lung metastases have been associated with a more favorable outcome. There are limited data available regarding the immune microenvironment at different anatomical sites of melanoma metastases. This study sought to characterize and compare the tumor immune microenvironment of liver, brain, lung, subcutaneous (subcut) as well as lymph node (LN) melanoma metastases. Methods: We analyzed OS in 1924 systemic treatment-naïve patients with AJCC (American Joint Committee on Cancer) stage IV [...]
Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting.
Abstract Background: The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective: To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods: We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10-8) [...]
Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome.
Abstract The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes [...]
Effect of the SunSafe Training Program on the attitudes, knowledge, and behaviour of Australian high school students towards sun safety: a prospective study
Abstract Background: The SunSafe Student Ambassador Program (SSSAP) in Australia uses the peer-to-peer learning environment to educate high-school students about sun-safety. Aims: To assess whether the SSSAP would improve knowledge, attitudes and behaviours towards sun safety in high-school students and whether this would be sustained at 3 months. Methods: An assessment survey was delivered before, immediately after and 3 months after participation in the SSSAP in 2019. Results: In total, 503 participants completed the pre-presentation survey, 274 completed the post-presentation survey, and 218 completed both. Immediately following presentation, the total composite score for all 18 knowledge questions increased from a mean ± SD [...]
Detailed spatial immunophenotyping of primary melanomas reveals immune cell subpopulations associated with patient outcome.
Abstract While the tumor immune microenvironment (TIME) of metastatic melanoma has been well characterized, the primary melanoma TIME is comparatively poorly understood. Additionally, although the association of tumor-infiltrating lymphocytes with primary melanoma patient outcome has been known for decades, it is not considered in the current AJCC melanoma staging system. Detailed immune phenotyping of advanced melanoma has revealed multiple immune biomarkers, including the presence of CD8+ T-cells, for predicting response to immunotherapies. However, in primary melanomas, immune biomarkers are lacking and CD8+ T-cells have yet to be extensively characterized. As recent studies combining immune features and clinicopathologic characteristics have [...]
ASO Author Reflections: What Is the Role of Surgery in Management of In-Transit Melanoma in the Modern Era?
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Anchored Multiplex PCR Custom Melanoma Next Generation Sequencing Panel for Analysis of Circulating Tumor DNA
Abstract Detection of melanoma mutations using circulating tumor DNA (ctDNA) is a potential alternative to using genomic DNA from invasive tissue biopsies. To date, mutations in the GC-rich TERT promoter region, which is commonly mutated in melanoma, have been technically difficult to detect in ctDNA using next-generation sequencing (NGS) panels. In this study, we developed a custom melanoma NGS panel for detection of ctDNA, which encompasses the top 15 gene mutations in melanoma including the TERT promoter. We analyzed 21 stage III and IV melanoma patient samples who were treatment-naïve or on therapy. The overall detection rate of the custom panel, based on BRAF/NRAS/TERT promoter [...]
Treatment of in-transit Merkel cell carcinoma by isolated limb infusion with cytotoxic drugs
Abstract Merkel cell carcinoma of the skin is a rare but aggressive malignancy, which predominantly affects older adults with fair skin. Isolated limb infusion (ILI) using melphalan and actinomycin D was first developed as a minimally invasive treatment option to treat unresectable metastatic melanoma confined to the limb. We report on a 62-year-old male with in-transit metastases (ITMs) treated with ILI to highlight the ongoing role this treatment has when all other therapies have been exhausted. At presentation, the patient had widespread ITMs in the right leg. Positron emission tomography scan demonstrated recurrent disease in the thigh and pelvis, [...]