Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.
Abstract Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 [...]
Long-term survival across Breslow thickness categories: findings from a population-based study of 210 042 Australian melanoma patients.
Abstract The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the 4 American Joint Committee on Cancer 8th edition T categories by analyzing Australian registry data for 210 042 melanoma patients diagnosed from 1982 to 2014. The 30-year incidence rates of death due to melanoma and nonmelanoma (with 95% confidence intervals [CIs]) were 7.1% (95% CI = 6.9% to 7.3%) and 32.8% (95% CI = 32.3% to 33.3%), respectively. For T2 melanomas, the corresponding rates were [...]
Neoadjuvant or perioperative therapy for melanoma metastasis in clinical practice: an international survey
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Neoadjuvant or perioperative therapy for melanoma metastasis in clinical practice: an international survey.
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Uncovering the molecular mechanisms of amelanotic/hypopigmented primary cutaneous melanoma
Abstract Background: Approximately 2-20% of cutaneous melanomas (CMs) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. Objectives: To investigate loss-of-function mutations in key pigmentation genes in matched germline and AHM, as well as pigmented melanoma (PM), tumour DNA samples. Methods: Analysis of clinical and histopathological characteristics - together with whole-exome sequencing data of 34 fresh frozen primary CMs, graded according to the amount of pigmentation present - was performed. Together with germline and somatic variant analysis, 30 samples had previously been analysed for copy number aberration (CNA) changes. This study focused on germline and somatic variants in [...]
Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.
Abstract Introduction: A diagnosis of melanoma in situ presents negligible risk to a person's lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients' management choices and anxiety levels. Methods and analysis: This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: 'melanoma in situ' (control), 'low-risk melanocytic neoplasm' (intervention 1) and 'low-risk melanocytic neoplasm, in situ' (intervention 2). The required sample [...]
The Development and Evaluation of a Convolutional Neural Network for Cutaneous Melanoma Detection in Whole Slide Images.
Abstract Context: The current melanoma staging system does not account for 26% of the variance seen in melanoma-specific survival, therefore our ability to predict patient outcome is not fully elucidated. Morphology may be of greater significance than in other solid tumors, with Breslow thickness remaining the strongest prognostic indicator despite being subject to high levels of interobserver variation. The application of convolutional neural networks to whole slide images affords objective morphologic metrics, which may reveal new insights into patient prognosis. Objective: To develop and evaluate a convolutional neural network for invasive cutaneous melanoma detection in whole slide images for [...]
Risk of Death Due to Melanoma and Other Causes in Patients With Thin Cutaneous Melanomas.
Abstract Importance: Most patients who present with primary cutaneous melanomas have thin tumors (≤1.0 mm in Breslow thickness, ie, pT1a and pT1b). Although their prognosis is generally considered to be excellent, there is limited precise information on the association of risk of death with specific Breslow measurements in thin lesions. Objective: To assess the relative effect of a 0.8-mm Breslow thickness threshold with respect to the incidence of both melanoma-related and nonmelanoma-related death. Design, setting, and participants: Registry data for all Australians diagnosed with thin invasive primary melanomas between 1982 and 2014 were analyzed. Data were extracted from all 8 Australian state [...]
Impact of Clinical Information on Melanocytic Skin Lesion Pathology Diagnosis: A Scoping Review
Abstract Importance: There is poor accuracy and reproducibility for the histopathologic diagnosis of melanocytic skin lesions, and the provision of clinical information may improve this. Objective: To examine the impact of clinical information on the histopathologic diagnosis of melanocytic skin lesions. Evidence review: PubMed, Embase, and Cochrane Library were searched for new records published from January 2018 to January 2024. References included in the 2018 Cancer Council Australia evidence review were also screened, and forward and backward citation searches were conducted. Findings: From 2224 records screened, 162 full-text studies were assessed, and 7 studies were included. Studies included pathologists from Austria, Germany, the [...]
Tissue-Based Profiling Techniques to Achieve Precision Medicine in Cancer: Opportunities and Challenges in Melanoma.
Abstract Immunotherapies targeting the programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) checkpoint receptors have revolutionized the treatment of metastatic melanoma. However, half of the treated patients do not respond to or eventually progress on standard therapies and many experience adverse events as a result of drug toxicity. The identification of accurate biomarkers of clinical outcomes are required in order to move away from the one-size-fits-all treatment approach of standard clinical practice and toward a more personalized approach to enable the administration of the optimal therapy for any given patient and further improve patient outcomes. Recent [...]