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 [...]
The Value of Sentinel Node Biopsy in Patients With Higher-Risk (T3, T4) Primary Cutaneous Melanomas: Insights Provided by a Stage II Risk Calculator.
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Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial.
Abstract Background: In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K. Methods: Change from baseline to week 53 in health-related quality of life (HRQoL), as measured using the EORTC QLQ-C30 and EQ-5D-5L utility index and visual analog scale (VAS), was compared between treatment groups using linear mixed-effect models. Time to confirmed deterioration (TTCD) in HRQoL was assessed using Cox regression. Bother from side effects, as measured by the FACIT-GP5, was descriptively compared between treatment groups. [...]
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 [...]
Clinical validation of droplet digital PCR assays in detecting BRAFV600-mutant circulating tumour DNA as a prognostic biomarker in patients with resected stage III melanoma receiving adjuvant therapy (COMBI-AD): a biomarker analysis from a double-blind, randomised phase 3 trial.
Abstract Background: Cell-free, circulating tumour DNA (ctDNA) is an established measure of minimal residual disease; however, it is not utilised in melanoma management. We investigated whether ctDNA measurements could predict survival outcomes during adjuvant targeted therapy or placebo treatment in stage III melanoma, thereby identifying patients at high risk and low risk of recurrence. Methods: Analytically validated mutation-specific droplet digital PCR assays were used to measure BRAFV600E or BRAFV600K ctDNA in patients aged 18 years or older who were enrolled in the COMBI-AD trial, which was a double-blind, randomised, phase 3 study of oral dabrafenib (150 mg twice daily) plus oral trametinib (2 [...]
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 [...]
Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.
Abstract Background: Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear. Patients and methods: In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined. Results: A total of 628 patients from 34 centres [...]
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 [...]
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 [...]