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Prognosis and Treatment of Cutaneous Melanoma
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Prognosis and Treatment of Cutaneous Melanoma

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

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 10762

Special Issue Editors

Prof. Dr. Eduardo Nagore

E-Mail Website1 Website2
Guest Editor
Department of Dermatology, Instituto Valenciano de Oncologia, 46001 Valencia, Spain
Interests: melanoma; prognosis; survival; epidemiology; pathogenesis; risk factors
Prof. Dr. Rajiv Kumar

E-Mail Website
Guest Editor
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
Interests: melanoma genetics; telomere biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In this Special Issue, the most relevant and updated information about characteristics that determine the prognosis of cutaneous melanomas will be addressed. This will include an in-depth analysis of factors related to the patient (genetic predisposition), as well as the pathologic and molecular characteristics of the tumor. A review of the current available evidence on adjuvant and neoadjuvant treatment and the treatment of advanced melanoma are also included in this issue. 

Prof. Dr. Eduardo Nagore
Prof. Dr. Rajiv Kumar
Guest Editors

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 short 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

  • prognosis
  • melanoma
  • adjuvant
  • germline
  • somatic
  • genetic
  • epigenetic
  • neoadjuvant

Published Papers (6 papers)

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Research

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20 pages, 3270 KiB  
Article
The Impact of Drug–Drug Interactions on the Toxicity Profile of Combined Treatment with BRAF and MEK Inhibitors in Patients with BRAF-Mutated Metastatic Melanoma
by Silvia Mezi, Andrea Botticelli, Simone Scagnoli, Giulia Pomati, Giulia Fiscon, Federica De Galitiis, Francesca Romana Di Pietro, Sofia Verkhovskaia, Sasan Amirhassankhani, Simona Pisegna, Giovanna Gentile, Maurizio Simmaco, Bjoern Gohlke, Robert Preissner and Paolo Marchetti
Cancers 2023, 15(18), 4587; https://doi.org/10.3390/cancers15184587 - 15 Sep 2023
Cited by 1 | Viewed by 1195
Abstract
Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug–drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy. Methods: In this multicenter, observational, and retrospective study, [...] Read more.
Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug–drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy. Methods: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated. Results: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient’s home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068). Conclusions: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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16 pages, 1425 KiB  
Article
Topographical and Chronological Analysis of Thin Cutaneous Melanoma’s Progressions: A Multicentric Study
by Emmanouil Chousakos, Daniela Zugna, Emi Dika, Aram Boada, Sebastian Podlipnik, Cristina Carrera, Josep Malvehy, Susana Puig, Celia Requena, Esperanza Manrique-Silva, Eduardo Nagore, Pietro Quaglino, Rebecca Senetta and Simone Ribero
Cancers 2023, 15(15), 3989; https://doi.org/10.3390/cancers15153989 - 6 Aug 2023
Cited by 2 | Viewed by 1144
Abstract
A great portion of cutaneous melanoma’s diagnoses nowadays is attributed to thin tumors with up to 1 mm in Breslow thickness (hereafter thin CMs), which occasionally metastasize. The objective of this study was to identify thin CM’s metastatic patterns from a topographical and [...] Read more.
A great portion of cutaneous melanoma’s diagnoses nowadays is attributed to thin tumors with up to 1 mm in Breslow thickness (hereafter thin CMs), which occasionally metastasize. The objective of this study was to identify thin CM’s metastatic patterns from a topographical and chronological standpoint. A total of 204 cases of metastatic thin CMs from five specialized centers were included in the study, and corresponding data were collected (clinical, epidemiological, histopathological information of primary tumor and the number, anatomical site, and time intervals of their progressions). First progressions occurred locally, in regional lymph nodes, and in a distant site in 24%, 15% and 61% of cases, respectively, with a median time to first progression of 3.10 years (IQR: 1.09–5.24). The median elapsed time between the first and second progression and between the second and third progression was 0.82 (IQR: 0.34–1.97) and 0.49 (IQR: 0.21–2.30) years, respectively, while the median survival time was about 4 years since first progression. Furthermore, the sequences of locations and time intervals of the progressions were associated with the clinicopathological and demographic features of the primary tumors along with the features of the preceding progressions. In conclusion, the findings of this study describe the natural history of thin CMs, thus highlighting the necessity to identify subgroups of thin CMs at a higher risk for metastasis and contributing to the optimization of the management and follow-up of thin CM patients. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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9 pages, 1421 KiB  
Article
Long-Term Follow-Up of Lentigo Maligna Patients Treated with Imiquimod 5% Cream
by S. Morteza Seyed Jafari, Flavia Folini-Huesser, Simone Cazzaniga and Robert E. Hunger
Cancers 2023, 15(5), 1546; https://doi.org/10.3390/cancers15051546 - 28 Feb 2023
Cited by 6 | Viewed by 1650
Abstract
Background: The study investigated the long-term efficacy of imiquimod 5% cream for LM, with a focus on disease recurrence and the possible prognostic factors of disease-free survival (DFS) in a cohort, with long-term follow-up. Methods: Consecutive patients with histologically confirmed LM were included. [...] Read more.
Background: The study investigated the long-term efficacy of imiquimod 5% cream for LM, with a focus on disease recurrence and the possible prognostic factors of disease-free survival (DFS) in a cohort, with long-term follow-up. Methods: Consecutive patients with histologically confirmed LM were included. Imiquimod 5% cream was applied until weeping erosion appeared on the LM-affected skin. The evaluation was performed through clinical examination and dermoscopy. Results: We analyzed 111 patients with LM (median age: 72 years, 61.3% women) with tumor clearance after imiquimod therapy, with a median follow-up of 8 years. The overall patient survival rates were 85.5% (95% confidence interval (CI): 78.5–92.6) and 70.4% (95% CI: 60.3–80.5) at 5 and 10 years, respectively. Among the 23 patients (20.1%) with relapse at follow-up, 17 (73.9%) were treated with surgery, five (21.7%) continued imiquimod therapy, and one (4.3%) underwent both surgery and radiotherapy. After adjustment for age and LM area in multivariable models, localization of LM in the nasal region was identified as a prognostic factor for DFS (HR = 2.66; 95% CI: 1.06–6.64). Conclusion: If surgical excision is not possible due to the patients’ age/comorbidities or critical cosmetic localization, imiquimod could provide optimal outcomes with an optimal risk of relapse for the management of LM. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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13 pages, 1662 KiB  
Article
Real Check RIO: A Real-World Analysis of Nivolumab in First Line Metastatic Melanoma Assessing Efficacy, Safety and Predictive Factors
by Vlad-Adrian Afrăsânie, Teodora Alexa-Stratulat, Bogdan Gafton, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Natalia Gherasim-Morogai, Irina Afrăsânie, Lucian Miron and Mihai-Vasile Marinca
Cancers 2023, 15(4), 1265; https://doi.org/10.3390/cancers15041265 - 16 Feb 2023
Viewed by 1529
Abstract
We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy [...] Read more.
We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy on a treatment-naive population. After a median follow-up of 36 months, the median progression free survival (PFS) was 26 months (95% CI, 15–36) and the median overall survival (OS) was 31 months (95% CI, 20.1–41.8). At 12 months after the initiation of immunotherapy, the percentage of patients alive was 70%, and at 24 months 62.5%. The most common adverse events observed were dermatological (23.5%) and grade ≥3 was identified in 4 (6.8%) patients. Multivariate analysis indicated that the presence of liver metastases (HR 4.42; 95% CI: 1.88–10.4, p = 0.001) and a neutrophils/lymphocytes ratio (NLR) were associated with poor survival (HR 3.21; 95% CI: 1.04–9.87, p = 0.04). Although retrospective data on a small group of patients were analyzed, we can conclude that our results in RIO are similar to those described in clinical trials and other real-world studies. Our study highlights the potential usefulness of liver metastases and NLR as novel predictive factors in clinical decision-making. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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14 pages, 952 KiB  
Article
Outcomes of Patients with Metastatic Melanoma—A Single-Institution Retrospective Analysis
by Lidia Szatkowska, Jan Sieczek, Katarzyna Tekiela, Marcin Ziętek, Paulina Stachyra-Strawa, Paweł Cisek and Rafał Matkowski
Cancers 2022, 14(7), 1672; https://doi.org/10.3390/cancers14071672 - 25 Mar 2022
Cited by 2 | Viewed by 1712
Abstract
Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median [...] Read more.
Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median follow-up was 31 months (6–108 months). The median PFS1 was 6 months (1–44 months). Second-line systemic treatment was applied in 27 patients (52%). The median PFS2 was 2 months (0–27 months), and the median OS was 31 months (6–108 months). Among the analyzed risk factors, only the presence of the BRAF mutation was statistically significant for disease recurrence after surgery. In patients undergoing anti-BRAF/MEK therapy, the median PFS1 was 7 months, and in patients undergoing mono-immunotherapy, 4 months. The 12- and 24-month PFS1 rates in the group treated with BRAF inhibitors were 29 and 7%, respectively, and in patients treated with mono-immunotherapy 13 and 0%, respectively (Z = 1.998, p = 0.04). The type of treatment used had no effect on OS (Z = 0.237, p > 0.05). Conclusion: Patients with the V600 mutation should be closely monitored. In the event of disease recurrence, treatment with BRAF/MEK inhibitors should be considered. The type of treatment used has no effect on OS. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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17 pages, 2107 KiB  
Systematic Review
The Association of Nevus-Associated Melanoma with Common or Dysplastic Melanocytic Nevus: A Systematic Review and Meta-Analysis
by Clio Dessinioti, Aggeliki Befon and Alexander J. Stratigos
Cancers 2023, 15(3), 856; https://doi.org/10.3390/cancers15030856 - 30 Jan 2023
Cited by 5 | Viewed by 2467
Abstract
Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM [...] Read more.
Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I2 statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39–63%) with high heterogeneity at I2: 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51–77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36–75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63–78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype. Full article
(This article belongs to the Special Issue Prognosis and Treatment of Cutaneous Melanoma)
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