Shifts in Cutaneous Melanocytic Tumor Diagnostic Terminology: Melanocytoma, MPATH-Dx V2.0 and the WHO Skin5.
Abstract In this Special Issue of the Journal of Cutaneous Pathology in memory of Dr. Martin C. Mihm, Jr, we highlight his many contributions over more than 50 years to the catalog of specific melanocytic tumor terminology. Dr. Mihm was an active participant in the International Melanoma Pathology Study Group (IMPSG). Discussions led to proposed recommendations for changes in the terminology of melanocytic tumors and their standardized diagnostic reporting. Histopathological reports of melanocytic tumors provide critical information that guides patient counseling and therapy. Importantly the pathology report must relay whether the melanocytic tumor is benign, intermediate, or malignant, and [...]
Management of Local Skin Reactions Caused by 5-FU 4% Cream for the Treatment of Actinic Keratosis: A Delphi Consensus.
Abstract Introduction: Treatments such as 4% 5-fluorouracil (5-FU) cream have demonstrated strong efficacy in lesion clearance of actinic keratosis; however, local skin reactions (LSR) during treatment remain a significant challenge, potentially affecting patient adherence. Objective: We sought to build consensus on management of LSR associated with 4% 5-FU using the Delphi methodology. Methods: Twenty-eight expert dermatologists participated in a 3-round Delphi process. Experts evaluated LSR management strategies, including emollients, antibiotics, steroids, and treatment discontinuation. Agreement levels were measured using a 7-point Likert scale. Consensus was categorized as high if >80% of votes were within the 5-7 rating range and low when >25% [...]
Reconsidering the surgical approach in cutaneous melanoma: does wide local excision after a complete diagnostic excision reduce the risk of recurrence?
Abstract Objectives: This study examines whether wide local excision (WLE) after complete diagnostic excision improves recurrence-free survival (RFS) in clinical stage I/II primary cutaneous melanoma. Background: Since the 1950s, melanoma treatment has included a two-step surgical approach, involving diagnostic excision followed by WLE. WLE aims to achieve locoregional disease control by eliminating potential microsatellites and, thus, minimising the risk of locoregional recurrence and melanoma-related death. However, its impact on RFS is unclear, while it adds morbidity and costs. Methods: This retrospective nationwide cohort study analysed pathology reports of a Dutch population-based cohort of newly diagnosed invasive cutaneous melanoma patients who underwent a [...]
External validation of a model to predict recurrence-free and melanoma-specific survival for patients with melanoma after sentinel node biopsy.
Abstract Background: Recently, a model to predict 5-year recurrence-free survival (RFS) and melanoma-specific survival (MSS) after sentinel lymph node biopsy (SLNB) was published. The aim of this study was to validate that model in a large independent international cohort. Methods: The database of the Sentinel Lymph Node Working Group (SLNWG) was analysed for patients with malignant melanoma who underwent SLNB. Patients with clinical stage III melanoma, a history of other malignancies, or receiving concomitant systemic therapies during follow-up were excluded. The model's predictive performance was evaluated using discrimination and calibration metrics in the eligible cohort. Decision curve analysis was performed to [...]
Absolute Risk of Developing a Second Primary Cancer After a First Primary Melanoma: An Australian Population-Based Cohort Study.
Abstract Understanding the absolute risk of developing a second primary cancer is important to guide patient surveillance and education. We aimed to examine the cumulative incidence and factors associated with development of a second primary cancer (melanoma versus other) after diagnosis of a first primary melanoma (invasive or in situ). We analysed a population-based study cohort of 154,695 people diagnosed with a first primary melanoma in New South Wales, Australia, between 1982-2019. The cohort was followed for future cancer incidence and vital status for a median of 7.0 years. We used Fine-Gray models to account for death as a [...]
Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040
Abstract Importance: Despite many cases being preventable, cutaneous melanoma remains the most serious skin cancer worldwide. Understanding the scale and profile of the disease is vital to concentrate and reinforce global prevention efforts. Objective: To examine global patterns of cutaneous melanoma in 2020 and to provide projected estimates of cases and deaths by 2040. Design, setting, and participants: This population-based study used the GLOBOCAN 2020 database for global epidemiological assessment of new cases and deaths due to invasive melanoma. Main outcomes and measures: Age-standardized incidence and mortality rates were calculated per 100 000 person-years by country, world region, and 4-tier level of human [...]
Circulating MicroRNAs: functional biomarkers for melanoma prognosis and treatment.
Abstract MicroRNAs (miRNAs) hold significant promise as circulating cancer biomarkers and unlike many other molecular markers, they can provide valuable insights that extend beyond tumour biology. The expression of circulating miRNAs may parallel the cellular composition and dynamic activity within the tumour microenvironment and reveal systemic immune responses. The functional complexity of miRNAs-where a single miRNA can regulate multiple messenger RNAs (mRNAs) to fine tune fundamental processes, and a single mRNA can be targeted by multiple miRNAs-underscores their broad significance and impact. However, this complexity poses significant challenges for translating miRNA research into clinical practice. In melanoma, specific miRNA [...]
Prognostic and predictive value of gastric acid suppressants in the EORTC 1325/KEYNOTE-054 randomized phase III trial of pembrolizumab vs placebo in resected stage III melanoma.
Abstract Background The gut microbiome plays a pivotal role in regulating immunity. Gastric acid suppressants (GAS) are known to alter the gut microbiome and might therefore modify response to immunotherapy in cancer patients. We estimated associations of GAS with recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in the EORTC 1325/KEYNOTE-054 trial. Methods Patients with resected stage III melanoma were randomized to receive 200 mg of pembrolizumab or placebo. Pembrolizumab prolonged RFS and DMFS (reported elsewhere). We used Cox models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between GAS at baseline, and RFS and [...]
ASO Author Reflections: A Cost-Effectiveness Decision About Groin Lymphadenectomy: Reflections from the EAGLE FM Randomized Trial.
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Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study.
Abstract Background: Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2). Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks (part 1). RFS was the primary end point; DMFS was secondary. Patients with recurrence following placebo or 17 cycles of pembrolizumab could cross over to or be rechallenged with pembrolizumab (part 2). Results: Median follow-up (n = 976) was 52.8 months (range, 39.4-64.8). RFS (HR, 0.62 [95 % CI, 0.50-0.78]) [...]