Publications by authors named "Akkooi A"

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.

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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.

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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.

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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 identification of deep SLNs in intra-abdominal and intra-thoracic sites were included.

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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.

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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 disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy.

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Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.

Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.

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Article Synopsis
  • A phase 3 trial found that 12 months of adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with high-risk stage III melanoma compared to placebo, with longer follow-up data available.
  • With a median follow-up of 6.9 years, the pembrolizumab group showed a 50% RFS at 7 years versus 36% for the placebo group, and a 54% DMFS compared to 42% in the placebo group.
  • The results indicated consistent positive outcomes across various melanoma subtypes, confirming the long-term benefits of pembrolizumab in improving survival metrics in these patients.
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Background: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity.

Objective: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS).

Methods: Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included.

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Background: Localization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described.

Methods: In this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included.

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Aims: We aimed to develop a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) module tailored for patients with advanced (resectable or unresectable stage III/IV) melanoma receiving immune checkpoint inhibitors or targeted therapy.

Methods: Following the EORTC QoL Group module development guidelines, we conducted phases 1 and 2 of the development process. In phase 1, we generated a list of health-related (HR)QoL issues through a systematic literature review and semi-structured interviews with healthcare professionals (HCPs) and patients with advanced melanoma.

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Article Synopsis
  • The management of localized cutaneous melanoma has advanced significantly due to new systemic therapies, necessitating an updated review of treatment strategies.
  • Recent clinical trials, like the SWOG1801, show that combining neoadjuvant and adjuvant anti-PD-1 therapy improves survival rates compared to traditional methods.
  • Future trials, such as the upcoming phase 3 Nadina trial, are expected to further refine the role of surgery and systemic treatments in melanoma, potentially decreasing the necessity for extensive surgical procedures.
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Article Synopsis
  • In a study comparing neoadjuvant (before surgery) and adjuvant (after surgery) immunotherapy for stage III melanoma, neoadjuvant treatment showed greater effectiveness.
  • The trial involved random assignment of 423 patients to receive either two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery, or surgery followed by 12 cycles of adjuvant nivolumab.
  • Results indicated a significantly higher 12-month event-free survival rate in the neoadjuvant group (83.7%) compared to the adjuvant group (57.2%), with neoadjuvant therapy leading to better patient outcomes and more major pathological responses despite a higher incidence of severe adverse events.
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• This ESMO Clinical Practice Guideline provides key recommendations for managing Merkel-cell carcinoma (MCC). • Recommendations are based on available scientific data and the multidisciplinary group of experts’ collective opinion. • The guideline covers clinical and pathological diagnosis, staging and risk assessment, treatment and follow-up.

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Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes.

Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database.

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Background: A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses to identify prognostic and predictive biomarkers.

Patients And Methods: Two cohorts of patients with macroscopic stage III melanoma from an ongoing biobank study were included.

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Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient's immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy.

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Background: The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage.

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Objective: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM).

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Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.

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Article Synopsis
  • The study focuses on measuring the size of melanoma tumors in sentinel nodes (SN) to decide on additional treatment for patients with stage III melanoma.
  • Measuring these tumors accurately is very important, especially when the size is around 1.0 mm.
  • The research showed that different pathologists often get different measurements for the same tumors, which can affect treatment decisions, especially if there are many small tumors involved.
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Background: While adjuvant therapy with anti-programmed cell death protein-1 (anti-PD1) for patients with resected stage III/IV melanoma has been shown to improve recurrence-free survival, the overall survival benefit remains uncertain. This study aims to evaluate the impact of adjuvant anti-PD1 therapy on the health-related quality of life (HRQOL) of patients with resected stage III/IV melanoma METHODS: Data was used from two melanoma registries in Australia and the Netherlands. Patients with resected stage III/IV melanoma treated with adjuvant anti-PD1 who completed a baseline and at least one post-baseline HRQOL assessment were included.

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Article Synopsis
  • Recent trials showed benefits of using adjuvant systemic therapy (pembrolizumab/nivolumab) for stage IIB or IIC melanoma, but also highlighted risks. Accurate predictions for recurrence-free survival (RFS) and overall survival (OS) can help patients balance risks and benefits.
  • Researchers created a multivariable risk prediction calculator using data from 3,220 stage II melanoma patients to estimate 5- and 10-year RFS and OS more accurately than the current AJCC-8 staging model.
  • The new MIA models demonstrated better prediction accuracy (C-statistics) for RFS and OS compared to AJCC-8 models and were validated externally
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