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Medical Sciences (Basel, Switzerland) Sep 2021Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From...
Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002-2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03-1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.
Topics: Aged; Female; Humans; Lymph Node Excision; Male; Melanoma; Middle Aged; Nail Diseases; Neoplasm Recurrence, Local; Retrospective Studies; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 34564082
DOI: 10.3390/medsci9030057 -
Clinical and Translational Medicine Mar 2023Cutaneous melanoma is a lethal form of skin cancer with morbidity and mortality rates highest amongst European, North American and Australasian populations. The... (Review)
Review
BACKGROUND
Cutaneous melanoma is a lethal form of skin cancer with morbidity and mortality rates highest amongst European, North American and Australasian populations. The developments of targeted therapies (TTs) directed at the oncogene BRAF and its downstream mediator MEK, and immune checkpoint inhibitors (ICI), have revolutionized the treatment of metastatic melanoma, improving patient outcomes. However, both TT and ICI have their limitations. Although TTs are associated with high initial response rates, these are typically short-lived due to resistance. Conversely, although ICIs provide more durable responses, they have lower initial response rates. Due to these distinct yet complementary response profiles, it has been proposed that sequencing ICI with TT could lead to a high frequency of durable responses whilst circumventing the toxicity associated with combined ICI + TT treatment. However, several questions remain unanswered, including the mechanisms underpinning this synergy and the optimal sequencing strategy. The key to determining this is to uncover the biology of each phase of the therapeutic response.
AIMS AND METHODS
In this review, we show that melanoma responds to TT and ICI in three phases: early response, minimal residual disease (MRD) and disease progression. We explore the effects of ICI and TT on melanoma cells and the tumour immune microenvironment, with a particular focus on MRD which is predicted to underpin the development of acquired resistance in the third phase of response.
CONCLUSION
In doing so, we provide a new framework which may inform novel therapeutic approaches for melanoma, including optimal sequencing strategies and agents that target MRD, thereby ultimately improving clinical outcomes for patients.
Topics: Humans; Melanoma; Skin Neoplasms; Neoplasm, Residual; Immunotherapy; Tumor Microenvironment
PubMed: 36967556
DOI: 10.1002/ctm2.1197 -
American Family Physician Oct 2020
Topics: Aged; Dermatofibrosarcoma; Diagnosis, Differential; Humans; Male; Mohs Surgery; Neoplasm Recurrence, Local; Skin Neoplasms; Thigh
PubMed: 32996753
DOI: No ID Found -
Seminars in Oncology Dec 2007Adoptive cell transfer therapy has developed into a potent and effective treatment for patients with metastatic melanoma. Current application of this therapy relies on... (Review)
Review
Adoptive cell transfer therapy has developed into a potent and effective treatment for patients with metastatic melanoma. Current application of this therapy relies on the ex vivo generation of highly active, highly avid tumor-reactive lymphocyte cultures from endogenous tumor infiltrating lymphocytes or on the genetic engineering of cells using antigen receptor genes to express de novo tumor antigen recognition. When autologous anti-tumor lymphocyte cultures are administered to patients with high-dose interleukin (IL)-2 following a lymphodepleting conditioning regimen, the cells can expand in vivo, traffic to tumor, and mediate tumor regression and durable objective clinical responses. Current investigation seeks to improve the methods for generating and administering the lymphocyte cultures, and future clinical trials aim to improve durable response rates and extend the patient populations that are candidates for treatment.
Topics: Adoptive Transfer; Antigens, Neoplasm; Genetic Therapy; Humans; Lymphocyte Depletion; Lymphocyte Subsets; Lymphocytes, Tumor-Infiltrating; MART-1 Antigen; Melanoma; Neoplasm Metastasis; Neoplasm Proteins; Skin Neoplasms
PubMed: 18083376
DOI: 10.1053/j.seminoncol.2007.09.002 -
Annals of Oncology : Official Journal... Oct 2010Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. The incidence of this rare tumor is increasing rapidly; the American Cancer... (Review)
Review
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. The incidence of this rare tumor is increasing rapidly; the American Cancer Society estimates for 2008 almost 1500 new cases in the USA. Thus, the incidence of MCC will exceed the incidence of cutaneous T-cell lymphoma. Moreover, the mortality rate of MCC at 33% is considerably higher than that of cutaneous melanoma. These clinical observations are especially disturbing as we are only recently beginning to understand the pathogenesis of MCC. For the same reason, the therapeutic approach is often unclear; reliable data are only available for the therapy of locoregional disease.
Topics: Carcinoma, Merkel Cell; Follow-Up Studies; Humans; Neoplasm Staging; Prognosis; Skin Neoplasms
PubMed: 20943647
DOI: 10.1093/annonc/mdq366 -
Journal of Translational Medicine Aug 2017Anti-programmed death (PD)-1 and PD-ligand (L)-1 checkpoint inhibitors have revolutionized the therapy of several cancers. Immunotherapy of cancer can offer long-term... (Review)
Review
Anti-programmed death (PD)-1 and PD-ligand (L)-1 checkpoint inhibitors have revolutionized the therapy of several cancers. Immunotherapy of cancer can offer long-term durable benefit to patients, is active regardless of tumour histology, has a unique immune-related safety profile, and can be used in combination with other cancer treatments. In addition, recent research has shown that immune-based therapy can be used as adjuvant therapy, that outcomes may be influenced by dose, and that clinical activity is observed in patients with brain metastases. Despite our increased understanding of these agents, there are still several important questions that need to be answered. These include strategies to overcome primary and acquired resistance, the influence of mutational status on treatment outcomes, the optimal duration of treatment, and the need to identify novel combination regimens that offer increased anti-tumour potency and/or reduced toxicity. Here we review recent developments in these areas, with particular focus on new data reported at the 2017 ASCO Annual Meeting.
Topics: Carcinogenesis; Cell Cycle Checkpoints; Drug Resistance, Neoplasm; Humans; Melanoma; Mutation; Skin Neoplasms
PubMed: 28789707
DOI: 10.1186/s12967-017-1278-5 -
Surgical Oncology Clinics of North... Apr 2015In-transit melanoma is an uncommon pattern of recurrence, but presents unique management challenges and opportunities for treatment. The clinical presentation usually... (Review)
Review
In-transit melanoma is an uncommon pattern of recurrence, but presents unique management challenges and opportunities for treatment. The clinical presentation usually involves from 1 to more than 100 small subcutaneous or cutaneous nodules, ranging from submillimeter to multiple centimeters in diameter. Regional chemotherapy techniques are a mainstay of treatment of patients without systemic disease spread. Future applications of regional therapy are likely to involve combination therapy with cytotoxic agents and novel immune modulators. Regional therapy provides distinct opportunities for the treatment of unresectable disease, and offers a unique platform for investigation of novel therapeutics in early-stage clinical trials.
Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Humans; Melanoma; Neoplasm Recurrence, Local; Skin Neoplasms
PubMed: 25769714
DOI: 10.1016/j.soc.2014.12.008 -
Annals of Oncology : Official Journal... Sep 2012Melanoma is one of the most aggressive forms of skin cancer. Furthermore, incidence rates are increasing. Until recently, no agent had been shown to improve survival... (Review)
Review
Melanoma is one of the most aggressive forms of skin cancer. Furthermore, incidence rates are increasing. Until recently, no agent had been shown to improve survival over supportive care and treatment guidelines recommended that patients with metastatic disease were entered into clinical trials. With so few treatment options available, there was a clear need for new, more effective treatments in this setting. Melanoma serves as a 'model' tumour for understanding immunity to cancer. Melanoma tumour-associated antigens were among the first cancer antigens to be identified and classified, with further studies showing that many of these are also expressed by other tumour types. In addition, melanoma regression has been associated with vitiligo, visibly confirming an active role of the immune system in this type of cancer, and spontaneous regression of primary melanomas has also been observed in some cases. These observations, relating to the activity of the immune system in melanoma, provided strong evidence that this tumour would be amenable to immunotherapy, with immunotherapies such as cytokines, adoptive cell transfer and T-cell modulators shown to be an effective therapeutic approach. Against this background, melanoma has long been at the cutting edge of immuno-oncology research and will likely continue to be used as a model tumour to increase our understanding of immuno-oncology and to inform development in other types of cancer.
Topics: Adoptive Transfer; Antigens, Neoplasm; Cytokines; Humans; Immunotherapy; Melanoma; Neoplasm Regression, Spontaneous; Skin Neoplasms; Treatment Outcome; Vitiligo
PubMed: 22918922
DOI: 10.1093/annonc/mds257 -
Annals of Oncology : Official Journal... Aug 2009Data are presented on the current incidence of melanoma with recent and predicted future trends illustrating a likely continuing increase in incidence. Risk factors for... (Review)
Review
Data are presented on the current incidence of melanoma with recent and predicted future trends illustrating a likely continuing increase in incidence. Risk factors for developing melanoma are discussed, including current known melanoma susceptibility genes. Phenotypic markers of high-risk subjects include high counts of benign melanocytic naevi. Other risk factors considered include exposure to natural and artificial ultraviolet radiation, the effect of female sex hormones, socioeconomic status, occupation, exposure to pesticides and ingestion of therapeutic drugs including immunosuppressives and non-steroidal anti-inflammatory drugs. Aids to earlier diagnosis are considered, including public education, screening and use of equipment such as the dermatoscope. Finally, the current pattern of survival and mortality is described.
Topics: Global Health; Humans; Melanoma; Neoplasm Invasiveness; Risk Factors; Skin Neoplasms; Survival Rate
PubMed: 19617292
DOI: 10.1093/annonc/mdp252 -
Current Treatment Options in Oncology Jun 2013Melanoma is the most aggressive of the cutaneous malignancies, causing more than 9,000 deaths in the past year in the United States. Historically, systemic therapies... (Review)
Review
Melanoma is the most aggressive of the cutaneous malignancies, causing more than 9,000 deaths in the past year in the United States. Historically, systemic therapies have been largely ineffective, because melanoma is usually resistant to cytotoxic chemotherapy. However, during the past few years, several targeted therapies have proved effective in this challenging disease. These recent advances have been facilitated by an improved understanding of the driving genetic aberrations of melanoma, particularly mutations in the mitogen-activated protein kinase (MAPK) pathway. Vemurafenib, a BRAF inhibitor, demonstrated an overall survival advantage in phase III trials and is an appropriate option for first-line therapy in metastatic BRAF mutant melanoma. Dabrafenib, another BRAF inhibitor, and trametinib, a MEK inhibitor, also have been shown to be effective in phase III trials for BRAF mutant melanoma and may be additional treatment options as monotherapy or in combination pending regulatory approval. Additionally, imatinib is a promising targeted therapy for patients whose tumors harbor a KIT mutation in exons 11 and 13. Although these targeted agents cause objective responses and clinical benefit in patients with metastatic melanoma, resistance invariably develops. New targets and strategies to overcome acquired resistance are urgently needed. Furthermore, no effective targeted therapy has been developed for NRAS mutant tumors or in melanomas with as yet unknown driver mutations. In this review, we discuss current molecular targeted treatment options and promising ongoing research to develop new strategies to treat melanoma.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Drug Delivery Systems; Drug Resistance, Neoplasm; Humans; Melanoma; Molecular Targeted Therapy; Mutation; Skin Neoplasms
PubMed: 23420410
DOI: 10.1007/s11864-013-0226-8