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European Journal of Surgical Oncology :... Mar 2024Surgery is the mainstay treatment of melanoma. However, even after radical resection the risk of relapses in majority of stage IIB-IV disease remains high. Currently,... (Review)
Review
Surgery is the mainstay treatment of melanoma. However, even after radical resection the risk of relapses in majority of stage IIB-IV disease remains high. Currently, the standard treatment after surgery in high risk patients is systemic adjuvant therapy administered up to one year based on the results of clinical trials indicating significant reduction of risk of relapses. All clinical trials in adjuvant setting were based as primary end-point on relapse-free survival, not overall survival, and they did not incorporate and validate biomarkers prospectively. A new therapeutic strategy in locoregional advanced melanomas becomes a preoperative treatment to further increase of the cure rates and decrease the duration of systemic therapy.
Topics: Humans; Melanoma; Skin Neoplasms; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Recurrence
PubMed: 38342039
DOI: 10.1016/j.ejso.2024.107969 -
Journal Der Deutschen Dermatologischen... Jan 2024The treatment of metastatic cutaneous melanoma was fundamentally improved by the discovery and introduction of immune checkpoint inhibitors, such as anti-PD-1 and... (Review)
Review
The treatment of metastatic cutaneous melanoma was fundamentally improved by the discovery and introduction of immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, and targeted therapy with BRAF and MEK inhibition. Unfortunately, many patients suffer a relapse due to resistance mechanisms that in part are mediated by organ-specific metastatic sites. Especially, brain and liver metastases are negative predictive factors for both treatment modalities. There is still high unmet clinical need to prevent and treat spread to these organs. Therefore, experimental research should focus on mechanisms of hepatic melanoma metastasis to better understand this process and to identify therapeutic targets.
Topics: Humans; Melanoma; Skin Neoplasms; Neoplasm Recurrence, Local; Liver Neoplasms; Immunotherapy; Proto-Oncogene Proteins B-raf
PubMed: 37884458
DOI: 10.1111/ddg.15233 -
Journal of Investigative Surgery : the... Dec 2023Malignant melanoma is a highly aggressive tumor, and lymph node metastasis significantly impacts the prognosis and treatment of this condition. Sentinel node biopsy, as... (Review)
Review
Malignant melanoma is a highly aggressive tumor, and lymph node metastasis significantly impacts the prognosis and treatment of this condition. Sentinel node biopsy, as a less invasive alternative to traditional dissection, offers convenience, safety, and improved efficiency in assessing local lymph node status. It provides valuable staging information and aids in determining appropriate follow-up treatment. The evolution and enhancement of technical and conceptual aspects associated with sentinel node biopsy have transformed the management of malignant melanoma. Notably, several large multicenter trials have challenged the necessity of complete lymph node dissection, leading to a paradigm shift. While some controversy remains, the standard of care for melanoma is progressing toward a consensus.
Topics: Humans; Sentinel Lymph Node Biopsy; Melanoma; Skin Neoplasms; Lymph Node Excision; Lymph Nodes; Melanoma, Cutaneous Malignant
PubMed: 37348854
DOI: 10.1080/08941939.2023.2225087 -
Cutis Dec 2023
Topics: Humans; Ad26COVS1; COVID-19; Hemangioendothelioma; Skin Neoplasms
PubMed: 38290076
DOI: 10.12788/cutis.0920 -
The British Journal of Dermatology Sep 2023
Topics: Humans; Lymphatic Metastasis; Melanoma; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 37395059
DOI: 10.1093/bjd/ljad218 -
The Australasian Journal of Dermatology Mar 2024The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed... (Review)
Review
The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.
Topics: Humans; Lymphatic Metastasis; Neoplasm Micrometastasis; Skin Neoplasms; Prognosis; Skin; Sentinel Lymph Node Biopsy; Neoplasm Staging
PubMed: 38156714
DOI: 10.1111/ajd.14206 -
International Journal of Molecular... May 2024Melanoma, a malignant neoplasm originating from melanocytes, stands as one of the most prevalent cancers globally, ranking fifth in terms of estimated new cases in... (Review)
Review
Melanoma, a malignant neoplasm originating from melanocytes, stands as one of the most prevalent cancers globally, ranking fifth in terms of estimated new cases in recent years. Its aggressive nature and propensity for metastasis pose significant challenges in oncology. Recent advancements have led to a notable shift towards targeted therapies, driven by a deeper understanding of cutaneous tumor pathogenesis. Immunotherapy and tyrosine kinase inhibitors have emerged as promising strategies, demonstrating the potential to improve clinical outcomes across all disease stages, including neoadjuvant, adjuvant, and metastatic settings. Notably, there has been a groundbreaking development in the treatment of brain metastasis, historically associated with poor prognosis in oncology but showcasing impressive results in melanoma patients. This review article provides a comprehensive synthesis of the most recent knowledge on staging and prognostic factors while highlighting emerging therapeutic modalities, with a particular focus on neoadjuvant and adjuvant strategies, notably immunotherapy and targeted therapies, including the ongoing trials.
Topics: Humans; Melanoma; Prognosis; Neoplasm Staging; Immunotherapy; Skin Neoplasms; Molecular Targeted Therapy; Disease Management; Protein Kinase Inhibitors
PubMed: 38891988
DOI: 10.3390/ijms25115794 -
Radiotherapy and Oncology : Journal of... Sep 2023Dermatofibrosarcoma protuberans (DFSP) is characterized by locally invasive growth patterns and high local recurrence rates. Accurately identifying patients with high...
BACKGROUND AND PURPOSE
Dermatofibrosarcoma protuberans (DFSP) is characterized by locally invasive growth patterns and high local recurrence rates. Accurately identifying patients with high local recurrence risk may benefit patients during follow-up and has potential value for making treatment decisions. This study aimed to investigate whether machine learning-based radiomics models could accurately predict the local recurrence of primary DFSP after surgical treatment.
MATERIALS AND METHODS
This retrospective study included a total of 146 patients with DFSP who underwent MRI scans between 2010 and 2016 from two different institutions: institution 1 (n = 104) for the training set and institution 2 (n = 42) for the external test set. Three radiomics random survival forest (RSF) models were developed using MRI images. Additionally, the performance of the Ki67 index was compared with the three RSF models in the external validation set.
RESULTS
The average concordance index (C-index) scores of the RSF models based on fat-saturation T2W (FS-T2W) images, fat-saturation T1W with gadolinium contrast (FS-T1W + C) images, and both FS-T2W and FS-T1W + C images from 10-fold cross-validation in the training set were 0.855 (95% CI: 0.629, 1.00), 0.873 (95% CI: 0.711, 1.00), and 0.875 (95% CI: 0.688, 1.00), respectively. In the external validation set, the C-indexes of the three trained RSF models were higher than that of the Ki67 index (0.838, 0.754, and 0.866 vs. 0.601, respectively).
CONCLUSION
Random survival forest models developed using radiomics features derived from MRI images were proven helpful for accurate prediction of local recurrence of primary DFSP after surgical treatment and showed better predicting performance than the Ki67 index.
Topics: Humans; Dermatofibrosarcoma; Retrospective Studies; Ki-67 Antigen; Skin Neoplasms; Neoplasm Recurrence, Local
PubMed: 37315580
DOI: 10.1016/j.radonc.2023.109737 -
Science (New York, N.Y.) May 2024Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks...
Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks from hundreds of mouse tissue samples (both normal and tumor) and integrated these with lineage tracing and single-cell RNA-seq, to identify convergence of cell states in premalignant tumor cells expressing markers of lineage plasticity and drug resistance. Two of these cell states representing multilineage plasticity or proliferation were inversely correlated, suggesting a mutually exclusive relationship. Treatment of carcinomas in vivo with chemotherapy repressed the proliferative state and activated multilineage plasticity whereas inhibition of differentiation repressed plasticity and potentiated responses to cell cycle inhibitors. Manipulation of this cell state transition point may provide a source of potential combinatorial targets for cancer therapy.
Topics: Animals; Mice; Skin Neoplasms; Carcinoma, Squamous Cell; Neoplastic Stem Cells; Cell Lineage; Single-Cell Analysis; Cell Differentiation; Drug Resistance, Neoplasm; Cell Plasticity; Cell Proliferation; Gene Regulatory Networks; RNA-Seq; Gene Expression Regulation, Neoplastic
PubMed: 38815020
DOI: 10.1126/science.adi7453 -
American Journal of Clinical Dermatology May 2024With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier... (Review)
Review
With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III-IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease. With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35-50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority. Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.
Topics: Humans; Melanoma; Skin Neoplasms; Immune Checkpoint Inhibitors; Biomarkers, Tumor; Neoadjuvant Therapy; Proto-Oncogene Proteins B-raf; Neoplasm Staging; Neoplasm Recurrence, Local
PubMed: 38409643
DOI: 10.1007/s40257-024-00852-5