Symptomatic acute hypotension associated with high-dose dacarbazine
We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with high-dose dacarbazine from January 2018 to August 2019 in Oscar Lambret Center, Lille, France. In our study, a total of 23 patients in outpatient care were analyzed, they underwent 57 treatment cycles. We observed 8 episodes of hypotension in 7 of the 23 consecutive treated patients (30.4%). We discuss herein several hypotheses explaining dacarbazine-induced hypotension. Dacarbazine high dose and administration methods seem to be the main causes of hypotension adve...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Short Communications: Clinical science Source Type: research

Conception and viable twin pregnancy in a patient with metastatic melanoma while treated with CTLA-4 and PD-1 checkpoint inhibition
In this report, we describe the successful pregnancy and clinical course of a patient diagnosed with metastatic melanoma who conceived twins while undergoing dual checkpoint blockade with ipilumumab and nivolumab. While there are case reports of patients receiving checkpoint inhibitors during pregnancy, our case is the first to describe a successful pregnancy that was conceived during treatment with combination anti-CTLA-4 and PD-1, with therapy continuing throughout pregnancy. This case adds to the growing evidence that favorable pregnancy outcomes may be possible while receiving checkpoint inhibition, which will hopefull...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Short Communications: Clinical science Source Type: research

Hibernoma as an incidental finding in the 18F-FDG PET/CT of a patient with melanoma
We present the case of a patient with cutaneous melanoma, diagnosed with a cervical hibernoma mimicking a metastatic lymph node at fluorine-18-fluorodeoxyglucose PET/CT. Being aware of the metabolic behavior and radiologic appearance of this entity may prevent reporting false-positive lesions, especially in an oncologic setting. (Source: Melanoma Research)
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Short Communications: Clinical science Source Type: research

Assessment of internet sources on subungual melanoma
In this study, we sought to objectively determine the accuracy and comprehensibility of online material with regard to subungual melanoma, a nail disease that is rare within the general population, yet has high incidence in certain patient groups, and carries a poorer prognosis than other forms of cutaneous melanoma. Because improved prognosis relies on early diagnosis, the dissemination of accurate, understandable information is an important factor in patient education and health. Using a pro forma designed to score website reliability, the accountability, quality, readability, display, support features, and transparency ...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Short Communications: Clinical science Source Type: research

Distinguishing melanophages from tumor in melanoma patients treated with talimogene laherparepvec
Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells (‘melanophages’) persist after injection, mimicking melanoma. We used quantitative immunofluorescence (qIF) to (1) distinguish melanophages from melanoma in biopsies from two patients treated with T-Vec and (2) evaluate the tumor microenvironment pretreatment and posttreatment. Tissues were stained with 4’,6-diamidino-2-phenylindole, cluster of differentiation (CD) 3, CD8, CD68, human leukocyte antigen-DR isotype (HLA-DR), and SRY-Box Transcription Factor 10 (SOX10), and multispec...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Short Communications: Basic science Source Type: research

Incidence rate and risk factors for suicide death in patients with skin malignant melanoma: a Surveillance, Epidemiology, and End Results analysis
The purpose of this study was to use the Surveillance, Epidemiology, and End Results database to identify the incidence rate and risk factors for suicide death in patients with skin malignant melanoma (MM) in the USA. We screened cases of skin MM in the SEER database. The balance of covariates between the two groups was examined by the χ2-test and Fisher’s exact test. Logistic regression was used to identify independent risk factors for committing suicide. A propensity 1: 2 matched analysis was applied to minimize the risk of bias. In total, 103 500 patients with skin MM were included in the study, of whom 623 ha...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology Source Type: research

What has changed in the epidemiology of skin melanoma in central Italy during the past 20 years?
The aim was to evaluate changes in skin melanoma incidence and mortality at a population level in central Italy over the past two decades. Skin melanoma incidence rate from 1994 to 2014, were retrieved from the Umbrian Cancer Registry (about 900 000 inhabitants). Changes from 1994–1999 to 2010–2014 in tumour and patient characteristics – sex, age (0–44, 45–64, ≥ 65 years), site (head and neck, trunk, limbs), morphology (superficial spreading, nodular, other), thickness (≤ 1, 1–2, 2–4,> 4) and stage I–II, III–IV – were evaluated. Trend...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology Source Type: research

Long-term relative survival from melanoma in Germany 1997–2013
This study aimed to provide recent 5-year and 10-year RS from melanoma, stratified by prognostic factors, and identify latest survival trends. Data from 12 German cancer registries were analysed. We included patients with primary cutaneous malignant melanoma (ICD-10: C43.X) diagnosed in 1997–2013 who were at least 15 years old. Five-year and 10-year RS were estimated by period analysis. For 10-year RS analyses, we excluded patients who were 75 years of age or older. Analyses were stratified by sex, age, histology, tumour stage, and body site. We included 82 901 patients, of whom 51% were women. The median age at diag...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology Source Type: research

Utilization and impact of immunotherapy in stage IV melanoma using the National Cancer Database
To evaluate factors affecting the utilization of immunotherapy and to stratify results based on the approval of ipilimumab in 2011 and PD-1 inhibitors in 2014, an analysis of available data from the National Cancer Database (NCDB) was performed. Stage IV melanoma patients were identified. Effects of immunotherapy on overall survival (OS) were assessed using Kaplan–Meier curves and Cox proportional hazards model. A total of 19 233 patients were analyzed and 1998 received immunotherapy. Between 2011 and 2013, and in 2014, 18.6 and 28.9% of patients received immunotherapy, respectively. Patients who received immu...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology Source Type: research

Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients
Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Staging 18F-FDG PET/CT influences the treatment plan in melanoma patients with satellite or in-transit metastases
Whole-body positron emission tomography/computed tomography (PET/CT) and brain magnetic resonance imaging (MRI) are commonly used to stage patients with palpable lymph node metastases from melanoma, but their role in patients with satellite and/or in-transit metastasis (S&ITM) is unclear. The aim of this study was to establish the diagnostic value of PET/CT and brain MRI in these patients, and to assess their influence on subsequent management decisions. In this prospective study, 25 melanoma patients with a first presentation of S&ITM who had no clinical evidence of palpable nodal or distant metastasis underwent w...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

The prognostic role of BRAF and WNT pathways activation in kinase inhibitors-naïve clinical stage III cutaneous melanoma
The results of local-regional advanced melanoma (stage III) management are still not satisfactory. Particularly, there is no personalized treatment in stage III melanoma patients due to the lack of useful classical pathological markers for prognostication of indolent or aggressive course of the disease. The aim of this study was to explore melanoma genomic landscape by means of the mutational profiling of 50 genes influencing carcinogenesis pathways in the randomly selected 93 kinase inhibitor-naïve (KI-naïve) stage III patients. The genomic alterations were found in 27 out of 50 tested genes and at least one pat...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Intracellular signaling modules linking DNA damage to secretome changes in senescent melanoma cells
Cellular senescence is a major barricade on the path of cancer development, yet proteins secreted from senescent cells exert complex and often discordant effects on subsequent cancer evolution. Somatic genome alternations driving the formation of nevi and melanoma are efficient inducers of cellular senescence. Melanocyte and melanoma cell senescence is likely to come into play as a key factor affecting the course of tumorigenesis and responsiveness to therapy; little mechanistic information has been generated, however, that substantiates this idea and facilitates its clinical translation. Here, we established and character...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic science Source Type: research

Tacrolimus and ascomycin inhibit melanoma cell growth, migration and invasion via targeting nuclear factor of activated T-cell 3
Melanoma is the most malignant form of skin cancer with high metastatic potential. Nuclear factor of activated T-cells (NFATs) are discovered as transcription factors that regulate the expression of proinflammatory cytokines and other genes during the immune response. Among five NFAT members, NFAT3 is exclusively not expressed in immune cells and its role in progression of different types of cancer remains controversial. Our previous study showed that NFAT3 was highly expressed in skin cancer compared with normal skin tissues and critical for melanoma cell survival and tumor growth. Here, we reported that knockdown of NFAT...
Source: Melanoma Research - July 30, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic science Source Type: research

The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma
We report a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. Acute cellular allograft rejection on initiation of PD-1 inhibitor was successfully reversed with methylprednisolone. By converting the patient to sirolimus and giving predose prednisolone, pembrolizumab was continued with stable renal function and an excellent oncological response. This case supports the efficacy of PD-1 inhibitors in patients who are chronically immunosuppressed, and suggests an approach to maintain...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Induced sarcoid-like reactions in patients with metastatic melanoma treated with dabrafenib and trametinib: a monocentric retrospective study
Combined BRAF and MEK inhibition is one of the first-line treatment strategies for patients with advanced BRAF-mutant melanoma. Sarcoid-like reactions (SLRs) have occasionally been described with melanoma systemic treatments such as immunotherapy or the BRAF inhibitor vemurafenib, but very few cases have been reported with dabrafenib and trametinib. Our aim was to better characterize SLR induced by this combination. We conducted a monocentric retrospective observational study among patients treated with dabrafenib and trametinib for BRAF-mutant advanced melanoma from January 2015 to March 2019. Patients presenting with his...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Dermatomyositis in a patient undergoing nivolumab therapy for metastatic melanoma: a case report and review of the literature
We present the case of a 63-year-old man with metastatic melanoma undergoing treatment with nivolumab who developed significant motor weakness, paresthesias of both hands, swollen fingers, and a pruritic rash over the face, chest, and upper back after two cycles. Creatine kinase was elevated. Electromyography revealed a myopathic pattern, muscle biopsy of the deltoid revealed an inflammatory myopathy, and skin biopsy showed interface dermatitis. There were no detectable autoantibodies except positive antinuclear antibody. He was diagnosed with immunotherapy-induced dermatomyositis, nivolumab was held, and he was treated wi...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Very late recurrence of iris melanoma: 45 years after treatment
Iris melanoma is a rare tumour that accounts for ~3–4% of all uveal melanoma cases. In the past, surgical resection was the sole treatement option, whereas nowadays, it has been replaced by brachytherapy as treatment of choice. Surgical resection is still in use in selected cases but combined with adjuvant radiotherapy in cases of incomplete resection. Herein, we report the case of a very late recurrence, 45 years after surgical resection. A literature review was performed to detect the latest recurrence reported to date and to understand the etiology behind very late recurrences. The role of multiple factors is disc...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Nonhomologous end-joining repair is likely involved in the repair of double-stranded DNA breaks induced by riluzole in melanoma cells
Our group described the oncogenic potential of a normal neuronal receptor, metabotropic glutamate receptor 1 (GRM1/mGluR1, gene/protein), when aberrantly expressed in melanocytes led to cell transformation in vitro and spontaneous metastatic tumors in vivo. Earlier, we demonstrated the accumulation of phosphorylated histone H2AX (γH2AX), a marker for DNA damage when mGluR1-expressing melanoma cells were treated with a functional inhibitor, riluzole. The precise mechanisms on how riluzole induces DNA damage in these cells are unknown. In an attempt to begin to identify possible DNA repair pathways that may be involved...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Epidemiology of cutaneous melanoma and melanoma in situ: a 10-year nationwide retrospective cohort study in South Korea
Numerous studies on the epidemiology of cutaneous melanoma (CM) have been reported for Caucasians, but rarely for Asian populations including Korea. The aim of this study was to investigate the epidemiology of CM and melanoma in situ (MIS) in the Korean population. We investigated a nationally representative sample cohort of over one million Koreans for patients diagnosed with CM and MIS. Annual and overall incidence rates, as well as the survival rate of CM during the study period (2004–2013), were estimated. Demographic factors associated with survival rates and other clinical features of CM and MIS were evaluated ...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of melanoma Source Type: research

A meta-analysis of melanoma risk in industrial workers
Industrial workers are exposed to occupational pollutants, which may cause diseases such as cancer, but links to melanoma are not established. The identification of industry-related risk factors for melanoma incidence and mortality might be of importance for workers, health providers, and insurance companies. To assess melanoma incidence and mortality among oil/petroleum, chemical, and electrical industry workers. All studies reporting standardized mortality ratios (SMR) and/or standardized incidence ratios (SIR) of melanoma in workers employed in oil/petroleum, chemical, and electrical industries were included. Random-eff...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of melanoma Source Type: research

Stage-specific incidence trends of melanoma in an English region, 1996–2015: longitudinal analyses of population-based data
The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996–2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was appar...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of melanoma Source Type: research

20-year assessment of metastatic latency and subsequent time to death after proton therapy for uveal melanomas
The aim of this study was to evaluate metastatic latency and survival after the occurrence of metastases in patients with choroidal/ciliary body melanoma treated with proton therapy. This was a retrospective cohort study. All consecutive patients with choroidal/ciliary body melanoma treated with proton therapy between 1991 and 2010 were included. Overall survival, specific survival (SS), local recurrence-free interval, and metastasis-free interval (MFI) were calculated. There were 508 patients. The mean follow-up was 239.4 months. Overall survival and SS rates were 57.2 and 67.6% at 10 years. Pre-equatorial tumor location,...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Validation of dabrafenib-trametinib prognostic groups in patients treated with vemurafenib and cobimetinib for advanced BRAF-mutated melanoma
Prognostic groups defined by lactate dehydrogenase concentration and number of organ sites containing metastases have been reported for patients treated with dabrafenib and trametinib for advanced melanoma. We aimed to validate these prognostic groups for patients treated with vemurafenib and cobimetinib in the coBRIM and BRIM-3 clinical studies. Eight hundred nine patients were included, 240 treated with vemurafenib plus cobimetinib and 569 with vemurafenib. For patients treated with vemurafenib and cobimetinib, both overall survival (P (Source: Melanoma Research)
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II)
In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, i...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM)
Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subs...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical research Source Type: research

Targeted germline sequencing of patients with three or more primary melanomas reveals high rate of pathogenic variants
Individuals with multiple primary melanomas have rates of germline CDKN2A pathogenic variants of 3%–18%, and are also frequent carriers of variants in the melanocortin-1 receptor. Few patients with numerous (≥3) primary melanomas have been studied with respect to these or other potential germline pathogenic variants. We investigated 46 patients with ≥3 primary melanomas (3, n = 17; 4, n = 14; 5–14, n = 15) to determine if higher rates of germline pathogenic variants of CDKN2A, MC1R, or other cancer genes could explain their extreme melanoma phenotype. Most (43/46, 93%) patients had variants in MC1R and 11...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational research Source Type: research

Gut microbial species and metabolic pathways associated with response to treatment with immune checkpoint inhibitors in metastatic melanoma
In this study, metagenomic shotgun sequencing was performed on freshly frozen pre-treatment stool samples from 25 patients (12 responders and 13 non-responders) with unresectable metastatic melanoma treated with immune checkpoint inhibitors. We observed no significant differences in alpha-diversity and bacterial prevalence between responders and non-responders (P> 0.05). In a zero-inflated multivariate analysis, correcting for important confounders such as age, BMI and use of antibiotics, 68 taxa showed differential abundance between responders and non-responders (false-discovery rate (Source: Melanoma Research)
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational research Source Type: research

The alternatively spliced RECK transcript variant 3 is a predictor of poor survival for melanoma patients being upregulated in aggressive cell lines and modulating MMP gene expression in vitro
The reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene was described as a tumor suppressor gene two decades ago. Recently, novel alternatively spliced products of this gene have been identified. Of these, the transcript variant 3 (RECKVar3) was shown to display tumor-facilitating effects in astrocytoma cells in vitro, with a higher RECKVar3/canonical RECK expression ratio being correlated with lower survival rates of patients. However, the regulatory mechanisms through which the cell controls the production and maintenance of these alternative transcripts, as well as their expression in other tumor type...
Source: Melanoma Research - May 2, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic science Source Type: research

Rapid evolution of acute kidney injury after initial infusion of pembrolizumab in a melanoma patient concurrently treated with RAF/MEK inhibitors
The use of either immune checkpoint blockade or RAF/MEK inhibitors represents standard of care treatment options for metastatic melanoma. Each class of these drugs has distinct response kinetics, adverse effects, and unique clinical challenges. Combination of immune checkpoint blockade and RAF/MEK inhibitors may result in rapid and durable responses, however, the potential adverse effects of such combinations are poorly characterized. Here, we describe the case of a patient with BRAF-mutant melanoma who received an initial infusion of anti-PD-1 therapy while taking RAF/MEK inhibitors and experienced severe acute kidney inj...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Genomic profiling of a dedifferentiated mucosal melanoma following exposure to immunotherapy
We present the case of a resected mucosal melanoma that on relapse underwent transformation to a dedifferentiated state. The relapsed tumour was phenotypically disparate and demonstrated loss of all typical melanoma-associated immunohistochemical markers. Furthermore, it demonstrated aggressive biological behaviour and immunotherapy resistance. We performed genomic profiling of the original and relapsed tumour to further elucidate the mechanisms underlying this rare phenomenon. Mass spectrometry-based single-nucleotide polymorphism genotyping technology was used to screen for mutations in the original and recurrent tumour....
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

The role of ipilimumab after anti-PD-1 treatment: two case reports and a literature review
Metastatic melanoma has been historically associated with a poor prognosis; however, the therapeutic landscape has experimented and impressive change in the last years due to rapid advances in the immunotherapy field. The first immunotherapy treatment for metastatic melanoma was ipilimumab (anti-CTLA-4), which showed a significant improvement of overall survival compared to chemotherapy. However, in 2015 anti-PD-1 pembrolizumab shown an improved overall survival, progression-free survival and response rate compared to ipilimumab with either a better toxicity profile. Moreover, other immunotherapy combinations and target th...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

New primary melanoma in a patient under triple therapy with vemurafenib, cobimetinib, and atezolizumab for metastatic melanoma
We present the unique case of a patient that developed an invasive NPM while under treatment with a combination of vemurafenib, cobimetinib, and atezolizumab. A 39-year-old white male was treated with vemurafenib, cobimetinib, and atezolizumab for a stage IV (T0, N3, M1) BRAF-V600E mutated malignant melanoma in the context of a clinical trial. Eight months from treatment initiation he was diagnosed with an NPM on his back that was found to be BRAF-wild type and neuroblastoma ras mutated, while he was in complete remission. Wide excision of the lesion followed, and the patient was not withdrawn from study treatment. Twenty-...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Time trends and age–period–cohort analysis of cutaneous malignant melanoma incidence rates in the Romagna Region (northern Italy), 1986–2014
In conclusion, the long-term upward incidence trend in the study area is stabilizing among women and an attenuation of the increasing trend is occurring among younger men in the most recent cohorts. These observations need to be confirmed with longer-term studies. (Source: Melanoma Research)
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of Melanoma Source Type: research

Estimated risk of progression of lentigo maligna to lentigo maligna melanoma
Little is known about the risk of progression of lentigo maligna to lentigo maligna melanoma. We determine the annual risk of progression of lentigo maligna to lentigo maligna melanoma by analysing a prospective population-based survey of recently diagnosed anterior (visible in a mirror) head and neck lentigo malignas and lentigo maligna melanomas. Six hundred eighty-two consecutive patients aged 18–80 years with non-recurrent lentigo maligna or lentigo maligna melanoma, diagnosed between 1 July 2015 and 20 April 2016, were identified from pathology notifications to the New South Wales Cancer Registry (Australia) and...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of Melanoma Source Type: research

External validation of the American Joint Committee on Cancer 8th edition melanoma staging system: who needs adjuvant treatment?
Now effective adjuvant therapy has arrived in melanoma, accurate staging and patient selection to optimize its risk/benefit ratio is crucial. The American Joint Committee on Cancer staging system is the most widely used and validated melanoma staging system, which recently released its 8th edition. We aimed to externally validate the prognostic and discriminatory ability for survival of the 8th edition compared to the 7th edition and evaluate prognostic factors. Prospective database of stage III melanoma (2000–2016). Prognostic factors for melanoma-specific survival and distant metastasis-free survival were analyzed....
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Nevi and Breslow thickness in melanoma: sex differences?
A large body of evidence in the scientific literature suggests that the numbers of common and atypical nevi are strong, independent risk factors for the occurrence of cutaneous malignant melanoma. Furthermore, some studies recently found an association between high nevus counts and an improved melanoma prognosis. The aim of this study was to investigate a possible relationship between the number of common and atypical nevi and melanoma prognostic factors. We carried out a retrospective analysis of patients with a histopathologically confirmed diagnosis of melanoma. These patients were treated at the Dermatology Clinic of t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Recurrence risk of early-stage melanoma of the external ear: an investigation of surgical approach and sentinel lymph node status
Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluat...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1
Uveal melanoma is a life-threatening disease for which data on germline predisposition are essentially limited to mutations in the BAP1 gene. Many risk factors are shared between uveal melanoma and cutaneous melanoma, and these include fair skin color and light eye color. We carried out a genome-wide association study on 590 uveal melanoma patients and 5199 controls. Using a P-value limit of 10−5 we identified 11 loci with related odds ratios for the risk alleles ranging from 1.32 to 1.78. The smallest P-value in the overall analysis reached 1.07 × 10−7 for rs3759710 at 14q32.11, which is intronic to TDP1...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research

Utility of histone H3K27me3 and H4K20me as diagnostic indicators of melanoma
In this study, we performed immunohistochemistry on tissue microarrays containing 100 patient tissue spots; 18 benign nevi, 62 primary, and 20 metastatic melanoma tissues. We stained for histone H3K27me3 and histone H4K20me to ascertain whether these histone PTMs could be used to distinguish different stages of melanoma. Loss of histone H4K20me was observed in 66% of malignant patient tissues compared to 14% of benign nevi. A majority (79%) of benign nevi had low histone H3K27me3 staining, while 72% of malignant patient tissues showed either a complete loss or had strong histone H3K27me3 staining. When we analyzed the stai...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research

Evolutionarily conserved resistance to phagocytosis observed in melanoma cells is insensitive to upregulation of pro-phagocytic signals and to CD47 blockade
Therapeutic activation of macrophage phagocytosis has the ability to restrain tumour growth through phagocytic clearance of tumour cells and activation of the adaptive immune response. Our objective for this study was to evaluate the effects of modulating pro- and anti-phagocytic pathways in malignant melanoma. In order to identify evolutionarily conserved mechanisms of resistance that may be important for melanoma cell survival, we utilized a multi-species approach and examined the phagocytosis of human, mouse, and dog melanoma cells. We observed that melanoma cells from all three species displayed unexpected resistance t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research

Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells
This study showed that low-level laser irradiation alone is not able to kill human normal fibroblast and human melanoma cancer cells. Preirradiation followed by treatment with PCA did not change the cell viability in human fibroblast significantly but reduced the cell viability in melanoma cells presumably through the apoptosis pathway. (Source: Melanoma Research)
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research

Proliferation index and pseudoprogression as predictors of the therapeutic efficacy of suicide gene therapy for canine melanoma
In our veterinary clinical trials, the combination of systemic immunotherapy with local herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) treatment induced tumor pseudoprogression as part of a strong local antitumor response. This phenomenon could be owing to tumor inflammation, increased vascular permeability and to different tumor growth rates before, during and after SG therapy. The proliferation index (PI: the fraction of viable cells in S, G2/M, and hyperdiploid phases) would reflect the in-vivo and in-vitro proportion of proliferating melanoma cells in the absence of treatment (PIB) or in response t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research

Ultraviolet radiation and cutaneous melanoma: a historical perspective
In this article, we summarize the research that eventually led to the classification of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We recall the pioneering works that led to the formulation of novel hypotheses on the reasons underlying the increasing burden of melanoma in light-skinned populations. It took long before having compelling evidence on the association between UV and melanoma, in particular, the importance of UV exposure during childhood for both the occurrence of melanoma and death. The role of UVA was established only after 2005. If molecular lesions caused by UV radiation are bett...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Review Article Source Type: research

The clinical characteristics of melanoma with BRAF V600R mutation: a case series study
We report our experience in treatment of seven patients with V600R-mutant melanoma, whose clinical records were available for review. Four patients in our cohort received BRAF inhibitors. Three patients demonstrated partial objective response to BRAF/MEK targeted therapy. V600R-mutant melanoma accounts for a significant number of cases even in single-institution practices. We believe that testing for BRAF-mutation status should include rare variants of this mutation. From our experience, the high rate of ulceration, male predominance and advanced age at diagnosis are features of melanoma with V600R mutation, which are simi...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

Neoadjuvant intravitreal ranibizumab treatment in high-risk ocular melanoma patients: a two-stage single-centre phase II single-arm study
Despite an established history of intraocular antivascular endothelial growth factor (anti-VEGF) agents therapy in a variety of ocular pathologies as well as other cancer forms, use in the primary treatment of uveal melanoma has not been well assessed. This was a two-stage therapeutic and exploratory phase II, non-randomised, single centre trial involving intraocular treatment with 0.5 mg in 0.05 ml of ranibizumab via six intravitreous injections over 6 months in patients with primary ocular melanoma that otherwise required radical surgery because of tumour size. Seven patients were recruited with a median age of 66 years....
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research

The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), and NY-ESO-1 antigen; the infiltration of CD3+ T cells; and the microsatellite instability (MSI) phenotype, as well as the relationship of each factor to survival in malignant melanoma patients. Malignant melanoma samples from 89 patients were stained by immunohistochemistry to evaluate PD-1, PD-L1, CD3+ tumor-infiltrating lymphocytes (TILs), NY-ESO-1, and MSI. PD-1 and PD-L1 were expressed in 19.1 and 32.6% of the 89 samples, respectively. There was a significant correlation between PD-1 and PD-L1 expression (r&t...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Nivolumab for patients with metastatic uveal melanoma previously untreated with ipilimumab: a single-institution retrospective study
The objective response and disease control rates were 7.1% and 42.9%, respectively (one partial response and five stable diseases). The median progression-free survival and overall survival were 10 (range, 4–105) and 60 (range, 5–105) weeks, respectively. Liver metastases in three patients were all programmed cell death-1 ligand negative. Lower lactate dehydrogenase, development of vitiligo, and a neutrophil-to-lymphocyte ratio less than 5 at week 6 were associated with favorable progression-free survival and overall survival; of these, only a neutrophil-to-lymphocyte ratio less than 5 at week 6 was statistical...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Absolute lymphocyte count as a prognostic biomarker for overall survival in patients with advanced melanoma treated with ipilimumab
Biomarkers are needed to estimate which patients benefit most from combination ipilimumab and nivolumab immunotherapy. Rigorous biomarker analyses from prior ipilimumab randomized studies without nivolumab are likely to inform which biomarker analyses should be prioritized when examining patients treated with the combination. For the first time, the current analyses investigate absolute lymphocyte count (ALC) in randomized, controlled trials of ipilimumab without nivolumab to assess whether ALC is prognostic or predictive of ipilimumab treatment benefit. Data included patients (n = 1136) treated in the two randomized, cont...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research

Frequency of mutations in BRAF, NRAS, and KIT in different populations and histological subtypes of melanoma: a systemic review
The presence of mutations of BRAF, NRAS, and KIT genes is recognized as playing a role during carcinogenesis. Our study aims to evaluate and review other studies that present the frequency of mutations of BRAF, NRAS, and KIT genes for different populations, and analyse correlation to their clinical-pathological characteristics and to the demographics of melanoma. Thirty-two articles were selected from a collection of published literature studying 6299 patients. The parameters for correlation to different variables were calculated by odds ratio, for random and single effects. 38.5% of patients present BRAF gene mutations, 1...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research