Prognostic Significance and Management of Sentinel Nodes in the Triangular Intermuscular Space of Patients with Melanoma.
Abstract Background The clinical significance of sentinel nodes (SNs) in the triangular intermuscular space (TIS) of patients with melanoma is poorly understood. This study aimed to determine their incidence and positivity rate, and to report their management and patient outcomes. Methods This was a single-institution retrospective cohort study of patients with unilateral or bilateral TIS SNs on lymphoscintigraphy treated between 1992 and 2017. Recurrence-free survival was analyzed. Results Lymphoscintigraphy identified TIS SNs in 266 patients. They were bilateral in 17 patients. Of the 2296 patients with a melanoma on the upper back, 259 (11%) had TIS SNs. Procurement of [...]
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 [...]
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) [...]
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 [...]
Time interval between diagnostic excision-biopsy of a primary melanoma and sentinel node biopsy: effects on the sentinel node positivity rate and survival outcomes
Abstract Introduction: The optimal time interval between diagnostic excision of a primary cutaneous melanoma and sentinel node (SN) biopsy is unknown. The current study sought to determine whether this interval influenced the SN-positivity rate, recurrence or survival. Methods: Data collected from 2004 to 2014 for a Dutch population-based cohort of patients with melanoma who underwent SN biopsy (SNB) within 100 days of initial diagnosis (n = 7660) and for a similarly specified cohort from a large Australian melanoma treatment centre (n = 3478) were analysed. Time to SNB was analysed continuously (in weeks) and categorically (per month). The effects of SNB [...]
Time interval between diagnostic excision-biopsy of a primary melanoma and sentinel node biopsy: effects on the sentinel node positivity rate and survival outcomes.
Abstract Introduction: The optimal time interval between diagnostic excision of a primary cutaneous melanoma and sentinel node (SN) biopsy is unknown. The current study sought to determine whether this interval influenced the SN-positivity rate, recurrence or survival. Methods: Data collected from 2004 to 2014 for a Dutch population-based cohort of patients with melanoma who underwent SN biopsy (SNB) within 100 days of initial diagnosis (n = 7660) and for a similarly specified cohort from a large Australian melanoma treatment centre (n = 3478) were analysed. Time to SNB was analysed continuously (in weeks) and categorically (per month). The effects of SNB [...]
Effect of the time interval between melanoma diagnosis and sentinel node biopsy on the size of metastatic tumour deposits in node-positive patients.
Abstract Introduction: This study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis. Methods: Data were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the [...]
Effect of the time interval between melanoma diagnosis and sentinel node biopsy on the size of metastatic tumour deposits in node-positive patients
Abstract Introduction: This study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis. Methods: Data were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the [...]
BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting
Abstract Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a [...]
BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.
Abstract Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a [...]