Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.
Abstract Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.8 months. Median PFS was 10.2 months (95% CI, 6.5 to 15.4) with nivolumab plus relatlimab and 4.6 months (95% CI, 3.5 to 6.5) with nivolumab (hazard ratio [HR], 0.79 [95% CI, 0.66 to 0.95]); median OS was 51.0 months [...]
Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies.
Abstract Purpose: To evaluate linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies. Patients and methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy [...]
Acceptability and appropriateness of a risk-tailored organised melanoma screening program: Qualitative interviews with key informants.
Abstract Introduction: In Australia, opportunistic screening (occurring as skin checks) for the early detection of melanoma is common, and overdiagnosis is a recognised concern. Risk-tailored cancer screening is an approach to cancer control that aims to provide personalised screening tailored to individual risk. This study aimed to explore the views of key informants in Australia on the acceptability and appropriateness of risk-tailored organised screening for melanoma, and to identify barriers, facilitators and strategies to inform potential future implementation. Acceptability and appropriateness are crucial, as successful implementation will require a change of practice for clinicians and consumers. Methods: This was a qualitative [...]
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 [...]
Incidental Disappearing Proficient Mis-Match Repair Colon Cancer in a Patient with Advanced Metastatic Melanoma and the Rare Complications of Immunotherapy.
Abstract Complete pathological response (cPR) to immunotherapy of proficient in mismatch repair (pMMR) colorectal cancer is a rare event. Here we present and discuss a case of an incidental pMMR colon cancer which had a cPR to combination immunotherapy given for the treatment of metastatic melanoma. Whilst the patient had a cPR to immunotherapy, his clinical course was complicated by secondary adrenal insufficiency from immunotherapy-related hypophysitis. This case highlights a number of emerging topics in immunotherapy and colorectal cancer, specifically the treatment and selection of pMMR tumours with immunotherapy and the balance of risk when managing oncological outcomes, side [...]
Clinical significance of intra-thoracic and intra-abdominal sentinel lymph nodes detected on lymphoscintigraphy in truncal melanoma patients.
Abstract Background: Although most melanomas drain to the more common major lymph node basins (axilla, groin, neck), rarely they drain to deep SLN locations such as intra-abdominal and intra-thoracic (including intercostal and internal mammary) sites, which pose a higher surgical risk and complexity for procurement. Our study is aimed at determining the rate of positivity and likelihood of recurrence in these nodal sites to guide management decisions for patients with truncal melanomas which drain to these 'deep' SLN locations. Methods: Retrospective data collected between May 2008 and May 2022 including all patients with truncal melanomas who underwent lymphoscintigraphy resulting in the [...]
Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma.
Abstract Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI. We retrospectively identified patients treated with ICI for advanced melanoma with long-term disease control, defined as not requiring a subsequent line of systemic therapy within 3 years of ICI commencement. We [...]
Update of clinical practice guidelines for the management of patients with sarcoma.
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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 [...]