Melanoma Research最新文献

Long follow-up time is needed for overall survival (OS) data to mature for early-stage melanoma. This retrospective study aimed to describe the relationships between OS and two intermediate endpoints - real-world recurrence-free survival (rwRFS) and real-world distant metastasis-free survival (rwDMFS) - for patients with stage IIB or IIC melanoma that was completely resected from 1 January 2008 to 31 December 2017, with follow-up to 31 December 2020. We used three different approaches to describe the relationships: estimates of correlation using Kendall τ rank correlation; comparisons of all-cause survival with/without recurrence or distant metastasis using adjusted Cox proportional hazard models; and landmark analyses of all-cause survival stratified by recurrence status at 1-5 years. During a 39-month median follow-up from surgical resection, 223/567 patients (39%) experienced recurrence, among whom 171/567 patients (30%) developed distant metastasis. Median OS from surgical resection was 117.6 months [95% confidence interval (CI), 104.7-not reached], median rwRFS was 49.8 months (95% CI, 39.6-61.0), and median rwDMFS was 70.9 months (95% CI, 58.4-89.1). We observed strong correlations between rwRFS and OS, and between rwDMFS and OS (Kendall τ of 0.73 and 0.82, respectively). Risk of death was significantly greater after recurrence (all-cause survival adjusted hazard ratio [HR], 7.48; 95% CI, 4.55-12.29) or distant metastasis (adjusted HR, 11.00; 95% CI, 6.92-17.49). Risk of death remained significantly elevated with recurrence or distant metastasis by landmark years 1, 3, and 5 after surgical resection. These findings support the use of recurrence/rwRFS and distant metastasis/rwDMFS as surrogate endpoints for OS after complete resection of stage IIB or IIC melanoma.

Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of sex disparity in melanoma. Post-transcriptional regulation of prostaglandin-endoperoxide synthase (PTGS2) mRNA occurs through a complex interplay of specific trans-acting RNA-binding proteins and microRNAs. MiR-146a is a key player in melanoma, modulating immune responses and tumor microenvironment (TME). Polymorphisms in PTGS2 gene rs20415GC have been associated with an increased risk of melanoma. Epistasis between polymorphisms rs20415GC was investigated by genotyping 453 melanoma patients and 382 control individuals. The effects of testosterone and 17β-estradiol were analyzed in keratinocytes and two melanoma cell lines. The rs2910164GG showed a higher risk in the presence of the genotype rs20417CC in the male population. Testosterone and 17β-estradiol act differently on PTGS2 and miR-146a expression, depending on the cell type. Testosterone augments PTGS2 gene expression in keratinocytes and miR-146a in melanoma cells. While 17β-estradiol only increases miR-146a expression in HaCaT cells. The present study indicates a sex-specific relation between miR-146a and PTGS2 polymorphisms with melanoma cancer risk. Testosterone and 17β-estradiol act differently on the expression of PTGS2 and miR-146a depending on the skin cell type.

Melanoma patients failing all approved treatment options have a poor prognosis. The antimelanoma activity of regorafenib (REGO), a multitargeted kinase inhibitor, has not been investigated in this patient population. The objective response rate and safety of REGO treatment in advanced melanoma patients was investigated retrospectively. Twenty-seven patients received REGO treatment. All patients had progressed on anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibition and BRAF/MEK inhibitors (in case of a BRAF V600 mutation). REGO was administered in continuous dosing and combined (upfront or sequentially) with nivolumab ( n  = 5), trametinib ( n  = 8), binimetinib ( n  = 2), encorafenib ( n  = 1), dabrafenib/trametinib ( n  = 9), or encorafenib/binimetinib ( n  = 7). The best overall response was partial response (PR) in five patients (18.5%) and stable disease in three patients (11.1%). Three of seven (42.8%) BRAF  V600mut patients treated with REGO in combination with BRAF/MEK inhibitors obtained a PR (including regression of brain metastases in all three patients). In addition, PR was documented in a BRAF V600mut patient treated with REGO plus anti-PD-1, and a NRASQ61mut patient treated with REGO plus a MEK inhibitor. Common grade 3-4 treatment-related adverse events included arterial hypertension ( n  = 7), elevated transaminase levels ( n  = 5), abdominal pain ( n  = 3), colitis ( n  = 2), anorexia ( n  = 1), diarrhea ( n  = 1), fever ( n  = 1), duodenal perforation ( n  = 1), and colonic bleeding ( n  = 1). Median progression-free survival was 11.0 weeks (95% confidence interval, 7.1-14.9); median overall survival was 23.1 weeks (95% confidence interval, 13.0-33.3). REGO has a manageable safety profile in advanced melanoma patients, in monotherapy as well as combined with BRAF/MEK inhibitors or PD-1 blocking monoclonal antibodies. The triplet combination of REGO with BRAF/MEK inhibitors appears most active, particularly in the BRAF V600mut patients.

A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced practice professionals, and primary care providers. This metric, however, has rarely been applied to residency clinics. We aimed to determine the NNB at the University of Colorado residency clinics. Moreover, we sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on NNB. This study is a retrospective analysis of biopsies performed from 2016 to 2022 at the Denver Health Medical Center and the Rocky Mountain Regional Veteran Affairs dermatology clinics. Differential diagnosis at the time of biopsy was searched for keywords including melanoma, melanoma in situ, and lentigo maligna. Skin biopsies that included re-excisions were excluded. The NNB was subsequently generated by dividing the number of biopsied lesions with suspected melanoma by the number of histologically confirmed melanomas. The data was further separated by pre-COVID-19 (2016-February 2020), COVID-19 shutdown period (March 2020-July 2020), and post-COVID-19 (March 2020-present). Demographic data, including age, sex, race, and Fitzpatrick type, were collected. There were 2230 biopsies with suspected melanoma in the differential diagnosis at both clinic sites from 2016 to 2022. Of these, 362 were histologically confirmed melanoma. Total NNB was 6.16. The pre-COVID-19 NNB was 5.86, and the post-COVID-19 NNB was 6.91. Residency clinics have NNB similar to published values of practicing dermatologists. Furthermore, within these clinics, the impact of the COVID-19 pandemic was appreciated by a relative, although statistically insignificant, increase in NNB.

The aim of the study is to use the Surveillance, Epidemiology, and End Results (SEER) database to develop a useful clinical nomogram that uses prognosis prediction for pediatric melanoma patients. We obtained clinical information on pediatric melanoma patients from the SEER database between 2000 and 2018. Each patient was split into a training cohort or a validation cohort at random. Results between various subgroups were compared using Kaplan-Meier analyses. We created a nomogram to calculate the probability of survival for pediatric patients with melanoma. The performance of nomograms was assessed using calibration and discrimination. To assess the clinical use of this newly created model, decision curve analysis was also performed. In this study, a total of 890 eligible patients were chosen at random and allocated to 70% of training cohorts (n = 623) and 30% of validation cohorts (n = 267). After applying the chosen various components to create a nomogram, validated indexes showed that the nomogram had a strong capacity for discrimination. The training set's and validation set's C-index values were 0.817 and 0.832, respectively. The calibration plots demonstrated a strong correlation between the observation and the forecast. The model has a good clinical net benefit for pediatric melanoma patients, according to the clinical decision curve. In conclusion, we created an effective survival prediction model for pediatric melanoma. This nomogram is accurate and useful for clinical decision-making. Still, more external confirmation is required.

Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight how the characteristics of vulvar melanoma differentiate it from classic cutaneous melanoma. Vulvar melanoma has different risk factors and clinical and dermoscopic characteristics; moreover, it has a higher recurrence rate and a greater likelihood of multifocality. Here, we present a case of a 44-year-old patient with two primary vulvar melanomas located on opposite sides of her vulva. The lesions were both flat, but they had distinct clinical and dermoscopic appearances. Melanoma of the genital tract is likely the result of a multifocal disorder of the melanocytes within the mucosa that inhabit the perineal squamous epithelium. The risk factors of vulvar melanoma differ from those of classical cutaneous melanomas. Vulvar melanoma occurs in an area shielded from ultraviolet radiation; the primary risk factors include chronic inflammatory disease, genetic susceptibility, irritant agents and viral infections. This case study reveals how a close examination of the genital area is important and how dermoscopy can aid in the differential diagnosis of vulvar lesions. Inspections of the genital area should be particularly thorough if a melanoma is detected there, given the higher risk of multifocality in that part of the body.

The majority of patients diagnosed with melanoma have thin melanomas (≤1 mm). Data on the rate and pattern of recurrence after a negative sentinel lymph node biopsy (SLNB) are sparse. We retrospectively searched our institutional database and retrieved the records of patients with thin melanomas who underwent an SLNB with negative results. We analyzed patterns of recurrence, time to recurrence, and mode of diagnosis. Thirteen of the 198 patients with thin melanomas and negative SLNB results had tumor recurrence (6.5%): two local in transit (15.4%), three regional (21.3%), and eight distant (61.5%). Distant recurrences tended to occur later than local or regional ones [median disease-free survival = 50 months (95% confidence interval: 36.1-63.9) vs. 34 and 15 months (95% confidence interval: 5.4-24.6), P = 0.005, respectively]. The percentage of patients with tumor thickness ≥0.8 mm was higher among those who sustained recurrence (84.6 vs. 64.9% for no recurrence, P = 0.04). The majority of patients with recurrence were not being followed up when diagnosed (69%), and they are presented because of clinical symptoms. Patients with recurrence had lower survival compared with those without recurrence (median: 118 months vs. ongoing survival, P < 0.001, respectively). Melanoma recurrence in patients with thin melanomas and negative SLNBs is rare, tends to be distant, and negatively affects prognosis. Recurrence tends to occur in patients with melanoma thickness ≥0.8 mm. Further studies are needed to identify patients with high recurrence risk and determine optimal follow-up protocols.

Mortality from cutaneous malignant melanoma (CMM) increased in the past, but trends have been favorable in more recent years in many high-income countries. However, incidence has been increasing in several countries. We provided an up-to-date overview of mortality trends from CMM. We analyzed death certification data from the WHO in selected countries worldwide from 1980 to the most recent available calendar years. We also reported incidence data derived from Cancer Incidence in Five Continents from 1990 to 2012. Separate analyses were performed for young adults aged 20-44 and middle-aged adults aged 45-64 years. Mortality from CMM in all age groups showed a favorable pattern in the majority of the countries considered. Mortality trends declined by 40 to 50% in Australia over the last decades, confirming the importance of prevention measures. Considering young adults aged 20-44, Australia, New Zealand and Northern Europe reported the highest death rates for both sexes (>0.90/100 000 in men and >0.60/100 000 in women) while Japan, the Philippines, and Latin America the lowest ones (<0.50/100 000 and <0.35/100 000 in men and women, respectively). Incidence trends were stable or upward in most countries, with higher rates among women. Our study highlights a global reduction of CMM mortality over the last three decades. The increasing awareness of risk factors, mainly related to UV exposure, along with early diagnosis and progress in treatment for advanced disease played pivotal roles in reducing CMM mortality, particularly in Australia.

Metastatic uveal melanoma (mUM) is a rare cancer with poor prognosis, but novel treatments are emerging. Currently, there are no mUM-specific health-related quality of life (HRQL) questionnaires available for clinical research. We aimed to explore how mUM and its treatment affect HRQL and assess the content validity of existing questionnaires. Participants were patients with mUM and healthcare professionals involved in their care. Qualitative data were collected using semi-structured interviews and focus groups. Data collection and analysis used an integrative approach involving inductive questions/coding to elicit new concepts and deductive questions/coding based on domains of existing HRQL questionnaires. Initial interviews/focus groups focussed on HRQL questionnaires designed for patients with uveal melanoma or liver metastases. As new concepts were elicited, domains and items from other questionnaires were subsequently added. Seventeen patients and 16 clinicians participated. HRQL concerns assessed by uveal melanoma-specific questionnaires were largely resolved by the time of metastasis. The Functional Assessment of Cancer Therapy - Immunotherapy Module (FACT-ICM) adequately captured most immunotherapy-related side effects during initial treatment cycles. However, most patients emphasised emotional impacts over physical ones, focussing on the existential threat posed by disease amidst uncertainty about treatment accessibility and effectiveness. Patients were also concerned with treatment burden, including time commitment, travel, need for hospitalisation, and expenses. The relative importance of HRQL issues varied over time and across treatment modalities, with no single questionnaire being sufficient. Pending further development and psychometric testing, clinical researchers may need to take a modular approach to measuring the HRQL impacts of mUM.