van Akkooi, Alexander

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Abstract Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management. Method: This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy. Results: One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median [...]

February 25th, 2025|Tags: , , , , , |Comments Off on Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Abstract Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial. Methods: Patients with resected high-risk stage IIIA, IIIB, or IIIC melanoma received 200 mg of pembrolizumab (n = 514) or placebo (n = 505) every 3 weeks for twelve months. Pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at approximately 42 months [...]

February 7th, 2025|Tags: , , , , |Comments Off on Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics – Update 2024.

Abstract This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality. The diagnosis of melanoma can be made clinically and must always be confirmed by dermoscopy. If melanoma is suspected, a histopathological examination is always required. [...]

January 17th, 2025|Tags: , , , , , , , , , |Comments Off on European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics – Update 2024.

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 [...]

December 20th, 2024|Tags: , , , , , |Comments Off on Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.

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 [...]

December 9th, 2024|Comments Off on Clinical significance of intra-thoracic and intra-abdominal sentinel lymph nodes detected on lymphoscintigraphy in truncal melanoma patients.

Adjuvant systemic therapy in melanoma: Relative versus absolute benefit; the number needed to treat (NNT) versus the number needed to harm (NNH)?

Abstract Adjuvant (ADJ) systemic therapy has transformed melanoma treatment during the past decade. There are, however, still important unanswered questions that lead to debates on the utility and place of ADJ therapy for melanoma. When ADJ trials are reported, they present a hazard ratio with a significant P-value. This illustrates the relative benefit of the ADJ therapy, but do not give insight into the absolute benefit for an individual patient. Number needed to treat (NNT) expresses the number of patients required to receive an intervention in order to prevent one event of interest. It is measured by taking the reciprocal of [...]

December 1st, 2024|Comments Off on Adjuvant systemic therapy in melanoma: Relative versus absolute benefit; the number needed to treat (NNT) versus the number needed to harm (NNH)?

Impact of an online risk prediction tool for sentinel node metastasis on clinical decision-making in melanoma care: A mixed methods study.

Abstract Background The decision to perform a sentinel lymph node biopsy (SLNB) procedure can be guided by risk prediction tools. We aimed to investigate the impact of an online risk prediction tool for sentinel node metastasis on clinical decision-making. Methods We conducted a mixed methods study using an online questionnaire and semi-structured interviews between April 2022 and March 2023. Australian clinicians and patients/carers who were using the Melanoma Institute Australia risk prediction tool were invited to participate. Results Sixty-one participants completed the questionnaire (52 clinicians including 36 general practitioners of whom 32 worked at skin cancer clinics; 14 surgeons; [...]

December 1st, 2024|Tags: , , , , |Comments Off on Impact of an online risk prediction tool for sentinel node metastasis on clinical decision-making in melanoma care: A mixed methods study.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment – Update 2024.

Abstract A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.0 mm or ≥ 0.8 mm with additional histological risk factors, although there is as yet no [...]

November 29th, 2024|Tags: , , , , , , |Comments Off on European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment – Update 2024.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Abstract Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies. Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide [...]

November 19th, 2024|Tags: , , , , , |Comments Off on Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.

Abstract Background: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of [...]

November 19th, 2024|Tags: , , , , |Comments Off on Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.
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