Nodal radioactivity after lymphoscintigraphy as a guide to sentinel node-positivity in melanoma patients
Abstract Objective: To determine how often the sentinel node (SN) with the highest gamma count after lymphoscintigraphy was metastasis-free in SN-positive melanoma patients. Background: SN biopsy (SNB) is a standard staging procedure for patients with primary cutaneous melanoma. After pre-operative radiotracer injection, intra-operative gamma counts are used, with blue dye localization, to guide SN retrieval. Sometimes only the "hottest" nodes are removed, but the reliability of predicting SN-positivity on the basis of a node's gamma count is uncertain. Methods: Patients who had a SNB and in whom ≥2 SNs were removed, at least one of which contained metastatic melanoma, were identified from [...]
Predictive Performance of the Clinicopathologic Gene Expression Profile (CP-GEP) in Identifying Cutaneous Melanoma Patients for Whom Sentinel Lymph Node Biopsy is Unnecessary: A Systematic Review and Meta-Analysis
Abstract Context & aim: Sentinel lymph node biopsy (SLNB) is an invasive procedure that detects microscopic nodal metastasis, crucial for accurate staging and optimal management. In melanoma, most patients who undergo the procedure have no sentinel lymph node (SLN) metastasis detected. The CP-GEP model (Merlin Assay) was developed to identify patients who do not have SLN metastases and who may therefore safely forgo SLNB, based upon clinicopathologic and gene expression features of the primary tumour. While the Merlin Assay has been validated by independent cohorts with relatively moderate sample sizes, this meta-analysis aims to assess the overall predictive performance of [...]
ASO Visual Abstract: Cartilage Resection in the Surgical Management of Ear Melanoma.
No abstract available Read Full Paper
Do BRAF-targeted therapies have a role in the era of immunotherapy?
Abstract Over half of cutaneous melanomas have BRAF mutations, with this mutation being more prevalent in younger patients who often present with more aggressive disease. BRAF-targeted therapy and checkpoint inhibitor immunotherapy have led to marked improvements in outcomes for patients with BRAF-mutant melanoma. Despite these advances, novel combinatorial strategies are vital given that more than half of advanced melanoma patients will still die due to melanoma. Translational evidence has suggested potential immunostimulatory effects of BRAF-targeted therapies, yet their combination with immunotherapy has shown limited clinical success. The pathways that lead to acquired resistance to targeted therapy, which may confer [...]
Federated deep learning enables cancer subtyping by proteomics.
Abstract Artificial intelligence applications in biomedicine face major challenges from data privacy requirements. To address this issue for clinically annotated tissue proteomic data, we developed a Federated Deep Learning (FDL) approach (ProCanFDL), training local models on simulated sites containing data from a pan-cancer cohort (n=1,260) and 29 cohorts held behind private firewalls (n=6,265), representing 19,930 replicate data-independent acquisition mass spectrometry (DIA-MS) runs. Local parameter updates were aggregated to build the global model, achieving a 43% performance gain on the hold-out test set (n=625) in 14 cancer subtyping tasks compared to local models, and matching centralized model performance. The approach's [...]
Cartilage Resection in the Surgical Management of Ear Melanoma.
Abstract Background: Melanoma of the ear accounts for approximately 1% of cutaneous melanomas. Management recommendations are based on small retrospective series and case reports. Resection of melanoma of the ear requires a delicate balance between disease clearance, preservation of function, and aesthetics. The role of cartilage resection in the wide excision of melanoma of the ear remains unclear. We aimed to compare outcomes in patients having wide excision of ear melanoma who had cartilage resected with those who had a cartilage-sparing approach. Methods: Data were obtained from the Melanoma Institute Australia (MIA) prospectively maintained database. All patients diagnosed with invasive melanoma [...]
Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort.
Abstract Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination BRAF-targeted therapy with anti-programmed cell death-1 in the neoadjuvant setting. However, research on [...]
Global Applicability of a Risk Prediction Tool for Sentinel Node Positivity in Patients With Primary Cutaneous Melanoma.
Abstract Importance: The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk calculator provides estimates of positivity for individual patients based on 6 standard clinicopathological parameters and the full 6-parameter model has been externally validated previously using US data. However, given its geographically widespread use, further validation is required to ensure its applicability to other populations. Objective: To further externally validate the MIA SN metastasis risk calculator and increase its precision by refinement of the 95% CIs. Design, setting, and participants: A retrospective multicenter cohort study was carried out using data from 4 continents, including the national Danish Melanoma Database and cancer [...]
Molecular Analysis of Cutaneous Sarcomatoid Neoplasms Frequently Identifies Melanoma Driver Variants.
Abstract Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group of tumors with diverse prognoses and management options. These include undifferentiated and dedifferentiated melanoma (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), and sarcomatoid squamous cell carcinoma. Diagnosis requires careful correlation between the clinicopathologic and molecular features, and the finding of a MAPK pathway variant commonly associated with melanoma may support the diagnosis of melanoma over other tumors in this group. To examine the frequency of typical melanoma-associated MAPK pathway-related variants (BRAF, NRAS, KIT, GNAQ, GNA11) among a cohort of primary cutaneous [...]