Pathological response calculation assessment remains accurate with reduced tumor bed examination following neoadjuvant immunotherapy in clinically detectable stage III melanoma
Abstract Background: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathological response, determined as percentage residual viable tumor (% RVT), provides critical prognostic information and informs management decisions. Here, we assessed accuracy of %RVT calculation when reduced tumor bed (TB) was examined and leverage these results proposing streamlined protocols for pathological examination. Patients and methods: Comprehensive histopathological examination was carried out on 134 patient specimens after neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by the initial International Neoadjuvant Melanoma Consortium (INMC) protocol was [...]
Study protocol of a randomised phase II trial of concurrent stereotactic body radiotherapy with immunotherapy versus immunotherapy alone in patients with 1-5 extracranial melanoma oligometastases (AXIOM)
Abstract Background: Immunotherapy has significantly improved survival in patients with metastatic melanoma, achieving objective response rates of 45-60% and long-term survival. However, there is scope and a need to further improve outcomes. Preclinical and early clinical data suggest synergistic effects between stereotactic body radiotherapy (SBRT) and checkpoint inhibitor immunotherapy with an acceptable safety profile. Methods: AXIOM is a phase II, multicentre, randomised trial designed to evaluate the effectiveness and safety of upfront SBRT to all radiologically identified metastasis with immunotherapy over historical immunotherapy alone (standard of care) in patients with 1-5 extracranial melanoma oligometastases. The sample size calculation is based on [...]
A dynamic recurrence risk prediction tool for adjuvant therapy in stage III melanoma
Abstract Background: Prognosis for AJCC stage III melanoma varies significantly. Adjuvant therapies, including pembrolizumab, nivolumab, and dabrafenib/trametinib, have markedly reduced recurrence risk, as shown in pivotal trials (Keynote-054, CheckMate-238, and Combi-AD). Despite these advancements, clinicians lack tools to dynamically assess recurrence risk across the patient journey. Patients and methods: Using pooled individual patient data (IPD) from Kaplan-Meier curves of these trials, we developed a tool to dynamically estimate relapse-free survival (RFS) and distant metastasis-free survival (DMFS) over time. Conditional survival analyses incorporated AJCC-8 substages, treatment regimens, and recurrence data. Results: The analysis included 2206 patients (IIIA: 174, IIIB: 768, IIIC: 1169, IIID: [...]
Sites of metastases before systemic treatment influence progression patterns and survival in stage IV melanoma patients
Abstract Background: Metastatic sites influence response rates to immune checkpoint inhibitors (ICI) and survival, suggesting anatomical locations impact treatment outcomes. This study examines how baseline metastatic sites affect progression patterns and survival in melanoma patients receiving first-line ICI or BRAF/MEK inhibitors (BRAF/MEKi). Methods: Metastatic site presence and lesion counts at baseline and progression were captured chronologically for 347 ICI-treated and 210 BRAF/MEKi-treated patients using a novel graph representation. This novel approach enabled systematic comparison of progression patterns post-therapy failure across patients by providing a standardized representation of patterns of progression in patients with distinct clinical histories. Associations of baseline metastatic sites [...]
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.
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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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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 [...]
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 [...]