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Cancers
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New Developments in the Treatment of Early-Stage and Advanced Melanoma
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New Developments in the Treatment of Early-Stage and Advanced Melanoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 8144

Special Issue Editor

Dr. Ellen Kapiteijn

E-Mail Website1 Website2
Guest Editor
Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Interests: (uveal) melanoma; thyroid and other endocrine cancers; colorectal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the previous one, "Advanced Melanoma", (https://www.mdpi.com/journal/cancers/special_issues/Advanced_Melanoma).

In recent years, new systemic treatment options have become available for patients with advanced melanoma. These treatments are also given in the (neo)adjuvant setting of earlier stages of melanoma.

BRAF/MEK inhibitors, which act through the strong inhibition of the mutated BRAF protein, have been used in targeted therapy as about half of the patients with melanoma have this mutation. This therapy is initially very effective, but the tumor usually acquires resistance to these drugs within a year after the start of treatment. It is also currently used in the adjuvant setting in stage III melanoma.

Moreover, patients can be treated with immunotherapy using checkpoint inhibitors, regardless of their mutation status. The systemic treatment with checkpoint inhibitors consists of antibodies that stimulate T lymphocyte activation by blocking co-inhibitory signals. Treatment with these therapies can lead to long-term responses lasting several years. Checkpoint inhibitors are also used as adjuvant treatment in stage II and III melanoma and in the neo-adjuvant setting in stage III melanoma. However, the disease remains progressive in approximately half of the advanced patients under treatment using these forms of therapy. Hence, new therapies and clinical trials are still needed.

However, most efficacy data have been collected from randomized phase III trials with strict inclusion and exclusion criteria. Thus, there is a need for real-life data from registries in which, e.g., older patients and patients with comorbidities are also included. In addition, questions remain on how to evaluate and follow up patients while on treatment and also thereafter.

This Special Issue of Cancers will present the latest research on the abovementioned topics in early stage and advanced melanoma.

Dr. Ellen Kapiteijn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • early stage and advanced melanoma
  • metastasis
  • prognostic factors
  • clinical trials
  • real-life data
  • radiological evaluation and follow up
  • targeted therapy immunotherapy
  • new developments

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Published Papers (4 papers)

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Research

15 pages, 2682 KiB  
Article
Optically Guided High-Frequency Ultrasound Shows Superior Efficacy for Preoperative Estimation of Breslow Thickness in Comparison with Multispectral Imaging: A Single-Center Prospective Validation Study
by Noémi Nóra Varga, Mehdi Boostani, Klára Farkas, András Bánvölgyi, Kende Lőrincz, Máté Posta, Ilze Lihacova, Alexey Lihachev, Márta Medvecz, Péter Holló, Gyorgy Paragh, Norbert M. Wikonkál, Szabolcs Bozsányi and Norbert Kiss
Cancers 2024, 16(1), 157; https://doi.org/10.3390/cancers16010157 - 28 Dec 2023
Cited by 2 | Viewed by 1701
Abstract
Melanoma is the most aggressive form of skin cancer that is known for its metastatic potential and has an increasing incidence worldwide. Breslow thickness, which determines the staging and surgical margin of the tumor, is unavailable at initial diagnosis. Novel imaging techniques for [...] Read more.
Melanoma is the most aggressive form of skin cancer that is known for its metastatic potential and has an increasing incidence worldwide. Breslow thickness, which determines the staging and surgical margin of the tumor, is unavailable at initial diagnosis. Novel imaging techniques for assessing Breslow thickness lack comparative data. This study evaluates optically guided high-frequency ultrasound (OG-HFUS) and multispectral imaging (MSI) for preoperative estimation of Breslow thickness and staging. We enrolled 101 patients with histologically confirmed primary melanoma and categorized them based on tumor thickness. Optically guided 33 MHz HFUS and MSI were utilized for the assessment. Our MSI-based algorithm categorized melanomas into three subgroups with a sensitivity of 62.6%, specificity of 81.3%, and fair agreement (κ = 0.440, CI: 0.298–0.583). In contrast, OG-HFUS demonstrated a sensitivity of 91.8%, specificity of 96.0%, and almost perfect agreement (κ = 0.858, CI: 0.763–0.952). OG-HFUS performed better than MSI in estimating Breslow thickness, emphasizing its potential as a valuable tool for melanoma diagnosis and patient management. OG-HFUS holds promise for enhancing preoperative staging and treatment decision-making in melanoma. Full article
(This article belongs to the Special Issue New Developments in the Treatment of Early-Stage and Advanced Melanoma)
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20 pages, 2686 KiB  
Article
Real-World Effectiveness, Safety, and Health-Related Quality of Life in Patients Receiving Adjuvant Nivolumab for Melanoma in Belgium and Luxembourg: Results of PRESERV MEL
by Anne Rogiers, Laurence Willemot, Laura McDonald, Hilde Van Campenhout, Guy Berchem, Celine Jacobs, Nathalie Blockx, Andrée Rorive and Bart Neyns
Cancers 2023, 15(19), 4823; https://doi.org/10.3390/cancers15194823 - 30 Sep 2023
Cited by 2 | Viewed by 1939
Abstract
Background: Nivolumab, an anti–programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study [...] Read more.
Background: Nivolumab, an anti–programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study evaluating the effectiveness and safety of adjuvant nivolumab in patients with completely resected stage III or stage IV melanoma in clinical practice in Belgium and Luxembourg. Methods: Patients were enrolled prospectively and retrospectively during a 2-year period (January 2019–January 2021), and will be followed for 5 years. The results reported here are for the second interim analysis (cutoff date 31 December 2021). The index date was the date of first administration of adjuvant nivolumab. Patients received nivolumab for up to 12 months per label. Outcomes included relapse-free survival (RFS), adverse events (AEs)/treatment-related AEs (TRAEs), and health-related quality of life (HRQoL; assessed in prospectively enrolled patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), Functional Assessment of Cancer Therapy—Melanoma (FACT-M), and EQ-5D-3L instruments). HRQoL was evaluated at group level (mean change in scores from baseline based on minimally important differences) and individual patient level (percentage of patients with clinically important scores based on threshold of clinical importance). Outcomes were analyzed descriptively. Results: The study enrolled 152 patients (125 prospective, 27 retrospective) at 15 hospitals in Belgium and Luxembourg. Minimum potential follow-up at time of analysis was 11.4 months. Median age was 60 years (range 29–85), and 53% of patients were male. At 12 and 18 months, the RFS rates were 74.7% (95% confidence interval (CI): 66.9–80.9) and 68.4% (95% CI: 60.0–75.5), respectively. Median RFS was not reached. Grade 3 or 4 TRAEs were reported in 14% of patients. AEs led to treatment discontinuation in 23% of patients. Deaths occurred in 3% of patients and were not related to treatment. Questionnaire completion rates for HRQoL were high at baseline (90–94%) and at 24 months (78–81%). In the group-level analysis for HRQoL, mean changes in scores from baseline remained stable and did not exceed prespecified thresholds for minimally important differences during and after treatment, except for a clinically meaningful improvement in FACT-M surgery subscale scores. In the individual patient-level analysis for EORTC QLQ-C30 subscales, the percentages of patients who reported clinically relevant scores for fatigue and cognitive impairment increased during treatment (at 9 months) compared with baseline. After treatment cessation (at 18 months), the percentage of patients who reported clinically relevant scores for fatigue decreased. However, the percentages of patients who reported clinically relevant scores for emotional, cognitive, and social impairment increased at 18 months compared with during treatment. Most patients with emotional impairment at 9 and 18 months did not experience disease recurrence (91% and 89%, respectively). Conclusions: These results confirm the real-world effectiveness and safety of nivolumab as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. Cancer-specific, disease-specific, and generic HRQoL were maintained during and after treatment. The percentage of patients reporting emotional and cognitive impairment increased after treatment cessation, emphasizing the need for further investigation and tailored supportive care in these patients. Full article
(This article belongs to the Special Issue New Developments in the Treatment of Early-Stage and Advanced Melanoma)
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17 pages, 1932 KiB  
Article
C-Reactive Protein and Lymphocyte-to-Monocyte Ratio Predict Recurrence in Stage III Melanoma Patients with Microscopic Sentinel Lymph Node Metastasis
by Viktoria Anna Sophie Schildbach, Susanne Horn, Guillermo Hidalgo-Gadea, Wibke Johannis, Cornelia Mauch and Cindy Franklin
Cancers 2023, 15(3), 702; https://doi.org/10.3390/cancers15030702 - 23 Jan 2023
Cited by 4 | Viewed by 1984
Abstract
Although adjuvant therapies with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors improve recurrence-free survival (RFS) in stage III melanoma patients significantly, prognostic factors are needed to identify patients with a high risk of disease recurrence. Therefore, the aim of our study was to [...] Read more.
Although adjuvant therapies with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors improve recurrence-free survival (RFS) in stage III melanoma patients significantly, prognostic factors are needed to identify patients with a high risk of disease recurrence. Therefore, the aim of our study was to investigate the prognostic potential of routinely collected blood parameters for stage III melanoma patients with microscopic sentinel lymph node (SLN) metastasis. Altogether, we retrospectively analyzed 138 stage III melanoma patients who were diagnosed with microscopic SLN metastasis at the skin cancer center of the University Hospital Cologne between 2011 and 2020 and who did not receive prior adjuvant therapy with ICI or BRAF/MEK-inhibitors. Univariate and multivariate Cox regression analyses, Kaplan–Meier survival analyses and receiver operating characteristic (ROC) curves were performed to assess the impact of preoperatively collected blood parameters and blood ratios on recurrence-free survival (RFS; primary endpoint) and overall survival (OS). A high neutrophil-to-lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR) and high C-reactive protein (CRP) value were significantly associated with shorter RFS in multivariate analysis. For LMR (cut-off 3.5) and for CRP (cut-off 3.0) this effect remained after dichotomization. CRP showed a stronger association with RFS than NLR or LMR, with the highest association being detected for the combination of low LMR and high CRP. Additionally, derived NLR ≥ 2.0 was significantly associated with shorter OS in multivariate analysis. In summary, our data suggest that CRP in combination with LMR should be considered as a marker for melanoma recurrence in stage III melanoma patients with microscopic SLN metastasis. Full article
(This article belongs to the Special Issue New Developments in the Treatment of Early-Stage and Advanced Melanoma)
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15 pages, 1415 KiB  
Article
Application of Electronic Health Record Text Mining: Real-World Tolerability, Safety, and Efficacy of Adjuvant Melanoma Treatments
by Sylvia A. van Laar, Ellen Kapiteijn, Kim B. Gombert-Handoko, Henk-Jan Guchelaar and Juliette Zwaveling
Cancers 2022, 14(21), 5426; https://doi.org/10.3390/cancers14215426 - 3 Nov 2022
Cited by 5 | Viewed by 1982
Abstract
Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review [...] Read more.
Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods: Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs. Full article
(This article belongs to the Special Issue New Developments in the Treatment of Early-Stage and Advanced Melanoma)
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