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Current Treatment Options in Oncology Jan 2019Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and... (Review)
Review
Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10-15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.
Topics: Combined Modality Therapy; Humans; Immunotherapy; Japan; Melanoma; Molecular Targeted Therapy; Randomized Controlled Trials as Topic
PubMed: 30675668
DOI: 10.1007/s11864-019-0607-8 -
Saudi Medical Journal Apr 2016Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at...
Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.
Topics: Aged; Humans; Male; Melanoma; Mouth Neoplasms
PubMed: 27052289
DOI: 10.15537/smj.2016.4.15017 -
American Journal of Clinical Dermatology Sep 2021Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate... (Review)
Review
Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.
Topics: Diagnosis, Differential; Female; Humans; Melanoma; Skin Neoplasms; Vulva; Vulvar Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 34125416
DOI: 10.1007/s40257-021-00614-7 -
The Journal of the American Osteopathic... Jun 2019Melanoma is currently the fifth most common cancer in the United States, resulting in more than 9000 deaths each year. Despite numerous improvements in the management of... (Review)
Review
Melanoma is currently the fifth most common cancer in the United States, resulting in more than 9000 deaths each year. Despite numerous improvements in the management of advanced melanoma, the cornerstone to ensuring a cure remains early detection. Both patient and physician awareness regarding the signs and symptoms of early melanoma remain paramount. As a result, much effort has been and continues to be expended in developing and refining effective diagnostic algorithms to help identify melanomas and differentiate them from nevi, such as the ABCDE rule (A for asymmetry, B for border irregularity, C for color variegation, D for diameter >6 mm, and E for evolution in lesion size, shape, or color). To assist in the detection of more subtle melanomas requires technology to augment a visual examination. Toward this end, a simple instrument called a dermatoscope has transformed not only the appreciation of the morphology of melanoma but also its growth dynamics. The discipline of dermoscopy has improved the detection of melanoma and other skin cancers, has resulted in the detection of thinner melanomas, and has helped improve the ability to differentiate nevi (benign lesions) from melanomas, which, in turn, has resulted in fewer biopsies of benign lesions. Since patients often first present to their primary care physicians for their health-related concerns, it is imperative that primary care physicians be able to recognize the lesions that are suspicious for melanoma. This review is intended to introduce osteopathic physicians to the dermoscopic features associated primarily with melanomas located on nonglabrous skin.
Topics: Dermoscopy; Diagnosis, Differential; Humans; Melanoma; Physical Examination; Skin Neoplasms
PubMed: 31135866
DOI: 10.7556/jaoa.2019.067 -
The New England Journal of Medicine Feb 2014Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial.
METHODS
We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (± SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3 ± 1.8% vs. 64.7 ± 2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7 ± 4.0% vs. 40.5 ± 4.7%; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1 ± 4.8% among those with metastasis versus 85.1 ± 1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0 ± 7.0% and 64.6 ± 4.9% (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted.
CONCLUSIONS
Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.).
Topics: Adult; Aged; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Observation; Sentinel Lymph Node Biopsy; Skin Neoplasms; Survival Rate
PubMed: 24521106
DOI: 10.1056/NEJMoa1310460 -
Nature Genetics May 2009Mutational activation of BRAF is the earliest and most common genetic alteration in human melanoma. To build a model of human melanoma, we generated mice with...
Mutational activation of BRAF is the earliest and most common genetic alteration in human melanoma. To build a model of human melanoma, we generated mice with conditional melanocyte-specific expression of BRaf(V600E). Upon induction of BRaf(V600E) expression, mice developed benign melanocytic hyperplasias that failed to progress to melanoma over 15-20 months. By contrast, expression of BRaf(V600E) combined with Pten tumor suppressor gene silencing elicited development of melanoma with 100% penetrance, short latency and with metastases observed in lymph nodes and lungs. Melanoma was prevented by inhibitors of mTorc1 (rapamycin) or MEK1/2 (PD325901) but, upon cessation of drug administration, mice developed melanoma, indicating the presence of long-lived melanoma-initiating cells in this system. Notably, combined treatment with rapamycin and PD325901 led to shrinkage of established melanomas. These mice, engineered with a common genetic profile to human melanoma, provide a system to study melanoma's cardinal feature of metastasis and for preclinical evaluation of agents designed to prevent or treat metastatic disease.
Topics: Alleles; Animals; Cell Line, Tumor; Cell Proliferation; Mechanistic Target of Rapamycin Complex 1; Melanoma; Mice; Mice, Transgenic; Multiprotein Complexes; Neoplasm Metastasis; PTEN Phosphohydrolase; Proteins; Proto-Oncogene Proteins B-raf; TOR Serine-Threonine Kinases; Transcription Factors
PubMed: 19282848
DOI: 10.1038/ng.356 -
Archives of Pathology & Laboratory... Mar 2011The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas,... (Review)
Review
CONTEXT
The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies.
OBJECTIVE
To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas.
DATA SOURCES
Selected literature.
CONCLUSIONS
About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing thickness, modified by ulceration, mitotic rate, and other attributes.
Topics: Female; Humans; Male; Melanoma; Middle Aged; Models, Biological; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Skin Neoplasms; Survival Rate
PubMed: 21366458
DOI: 10.5858/2009-0479-RA.1 -
International Journal of Molecular... Sep 2022Melanoma is considered a multifactorial disease etiologically divided into melanomas related to sun exposure and those that are not, but also based on their mutational... (Review)
Review
Melanoma is considered a multifactorial disease etiologically divided into melanomas related to sun exposure and those that are not, but also based on their mutational signatures, anatomic site, and epidemiology. The incidence of melanoma skin cancer has been increasing over the past decades with 132,000 cases occurring globally each year. Marine organisms have been shown to be an excellent source of natural compounds with possible bioactivities for human health applications. In this review, we report marine compounds from micro- and macro-organisms with activities in vitro and in vivo against melanoma, including the compound Marizomib, isolated from a marine bacterium, currently in phase III clinical trials for melanoma. When available, we also report active concentrations, cellular targets and mechanisms of action of the mentioned molecules. In addition, compounds used for UV protection and melanoma prevention from marine sources are discussed. This paper gives an overview of promising marine molecules which can be studied more deeply before clinical trials in the near future.
Topics: Aquatic Organisms; Humans; Incidence; Melanoma; Skin Neoplasms
PubMed: 36142196
DOI: 10.3390/ijms231810284 -
Annals of Oncology : Official Journal... Aug 2009Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques--DNA and RNA... (Review)
Review
Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques--DNA and RNA microarrays--have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers--lactate dehydrogenase, S100B and melanoma-inhibiting activity--as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future.
Topics: Biomarkers, Tumor; Humans; Melanoma; Prognosis; Skin Neoplasms
PubMed: 19617299
DOI: 10.1093/annonc/mdp251 -
Ugeskrift For Laeger Nov 2023Disturbances of the nail apparatus are common and mainly benign. This review aims to investigate the aetiology of these disturbances, which range from more common benign... (Review)
Review
Disturbances of the nail apparatus are common and mainly benign. This review aims to investigate the aetiology of these disturbances, which range from more common benign causes to less common melanomas. Melanonychia may be the most prominent concern and is characterised by brown or black nail plate discoloration. Hence, understanding the most common nail changes, their epidemiology, pathophysiology, and clinical features are imperative to diagnosis and may prevent unnecessary surgical procedures in cases where it is not warranted.
Topics: Humans; Skin Neoplasms; Dermoscopy; Melanoma; Nails; Nail Diseases
PubMed: 38018740
DOI: No ID Found