Risultati per: Melanoma cutaneo

This cohort study investigates the association among different immunosuppressive regimens for grade 3 and higher immune-related adverse events with overall survival and progression-free survival in a homogeneous cohort of patients with advanced melanoma who were treated with first-line ipilimumab and nivolumab.

To the Editor We agree with the title of the Editorial by Swerlick, but it omits the considerable efforts to mount a randomized clinical trial in Australia. We assessed melanoma screening in 1992, recommending a randomized clinical trial at ages 45 to 69 years to assess mortality. Subsequently, a similar trial based on whole-body examinations by primary care practitioners (PCPs) was proposed. A pilot phase showing that screening increased enough to allow detection of a 20% reduction in mortality over 15 years was reported in 2002. The trial cost approximately $8.4 million; after national and international peer review, the research costs were approved, which were approximately half the total. However, the other costs, including payments to PCPs for the screening examinations, were not funded. Thus, the full trial was not conducted.

In Reply I thank Elwood et al for highlighting their previous efforts to develop more robust evidence to guide melanoma screening efforts. However, their work found similar findings as Matsumoto et al, with increased thin melanoma ascertainment in patients who had undergone screening skin examinations. While they modeled possible associations with mortality based on thickness data, their work did not look at actual mortality, either all cause or melanoma related.

This cross-sectional ecological study assesses the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence in the US.

Circulation, Volume 146, Issue Suppl_1, Page A11801-A11801, November 8, 2022. Introduction:The accumulation of senescent cells during aging relates to the development of various age-related pathologies including atherosclerosis and heart failure, which can be improved by specific elimination of senescent cells, so called “senolysis”. We have identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as an antigen specifically expressed by senescent endothelial cells, so called “seno-antigen”. Also, we previously developed the vaccine against Gpnmb, eliminated senescent cells in mice, leading to an improvement of age-related pathologies. However, detailed function of GPNMB in senescent cells is still uncertain.Purpose:To elucidate the role of GPNMB in senescent cells and cardiovascular-related pathologies.Methods:Overexpression or depletion of GPNMB in endothelial cells (ECs) were generated. Cellular senescence was induced in ECs by doxorubicin. Gpnmb-knockout or overexpressed (Gp-KO or Gp-OE) mice were generated and imposed to hind-limb ischemia treatment or high-fat-diet feeding to evaluate vascular functions. Double transgenic mice (ApoE-KO and Gp-KO or Gp-OE) were also generated and imposed to high-fat diet to develop atherosclerosis.Results:The depletion of GPNMB in ECs was proved to shorten their replicative lifespan, and increase the expression of negative cell cycle regulators including p53, p21 and p16. Conversely, overexpressed GPNMB protected ECs from senescence stress.In vivostudies showed the impairment of vascular function, atherogenesis, and endothelium-dependent vasodilatation were enhanced in Gp-KO mice, but attenuated in Gp-OE mice. Furthermore, GPNMB was found to localize on lysosomal membrane. Cells with depleted GPNMB demonstrated the accumulation of dysfunctional lysosomes, indicated the contribution of GPNMB in maintaining lysosome integrity. Under senescence-associated lysosomal stress, elevated GPNMB expression was detected, contributing to senescent cells survival.Conclusions:GPNMB acts as a protective factor to senescent cells. Seno-antigen targeting GPNMB is possibly considered as an efficient strategy against cardiovascular diseases and other age-associated disorders with higher selectivity and fewer off-target effects.

Circulation, Volume 146, Issue Suppl_1, Page A15638-A15638, November 8, 2022. Epidemiological studies have shown that the incidence of various cancers, such as malignant melanoma is higher in patients with heart failure (both HFrEF and HFpEF) than in age-matched population, but the underlying mechanisms remain unknown. We hypothesized that in HFpEF a chronic systemic inflammation promotes malignant melanoma progression. To test this hypothesis orthotopic melanoma xenograft model was employed in a mouse model of HFpEF. Mice with uninephrectomy, aldosterone infusion (UNX-Aldo) with osmotic minipump (Alzet, 0.30 μg/h), and high salt ingestion (1% in drinking water) develop left ventricle diastolic dysfunction as indicated by a significantly (p

This systematic review and meta-analysis assesses whether low-dose methotrexate exposure is associated with a higher risk of cutaneous melanoma.

Tens of thousands of patients would need to receive low-dose methotrexate to cause one case of melanoma.

Introduction
Australia has the highest incidence of melanoma in the world with variable care provided by a diverse range of clinicians. Clinical quality registries aim to identify these variations in care and provide anonymised, benchmarked feedback to clinicians and institutions to improve patient outcomes. The Australian Melanoma Clinical Outcomes Registry (MelCOR) aims to collect population-wide, clinical-level data for the early management of cutaneous melanoma and provide anonymised feedback to healthcare providers.

Methods and analysis
A modified Delphi process will be undertaken to identify key clinical quality indicators for inclusion in the MelCOR pilot. MelCOR will prospectively collect data relevant to these quality indicators, initially for all people over the age of 18 years living in Victoria and Queensland with a melanoma diagnosis confirmed by histopathology, via a two-stage recruitment and consent process. In stage 1, existing State-based cancer registries contact the treating clinician and provide an opportunity for them to opt themselves or their patients out of direct contact with MelCOR. After stage 1, re-identifiable clinical data are provided to the MelCOR under a waiver of consent. In stage 2, the State-based cancer registry will approach the patient directly and invite them to opt in to MelCOR and share identifiable data. If a patient elects to opt in, MelCOR will be able to contact patients directly to collect patient-reported outcome measures. Aggregated data will be used to provide benchmarked, comparative feedback to participating institutions/clinicians.

Ethics and dissemination
Following the successful collection of pilot data, the feasibility of an Australia-wide roll out will be evaluated. Key quality indicator data will be the core of the MelCOR dataset, with additional data points added later. Annual reports will be issued, first to the relevant stakeholders followed by the public. MelCOR is approved by the Alfred Ethics Committee (58280/127/20).

To the Editor We read with interest the article by Adamson et al regarding overdiagnosis of malignant melanoma (MM). The authors attribute to overdiagnosis the increasing incidence of MM in non-Hispanic White patients, which is not accompanied by an increase in mortality after adjusting for the incidence to mortality ratios in Black patients. We do not dispute that overdiagnosis occurs, as has been shown in randomized clinical trials of life-saving screening with computed tomography scans or mammography for other cancers. Rather, we contend that for melanoma, there is a real increase in incidence, and that the morbidity and costs associated with overdiagnosis do not outweigh the potential reduction in morbidity and death of melanoma primary prevention and early detection.

In Reply We are pleased that Paiva and Weinstock agree that overdiagnosis occurs in melanoma (and other cancers), as the evidence for its existence is overwhelming. As we indicated in our article, part of the rise in melanoma represents true disease, which is mostly concentrated among White men, the only demographic group for whom melanoma mortality was increasing before the advent of immunotherapy and targeted therapy for metastatic melanoma. However, true increases in melanoma mortality must be placed in the proper context; while melanoma mortality increased slightly from 1975 to 2013 (about 1 per 100 000; from 2.3 to 3.1 per 100 000), melanoma incidence increased markedly (about 45 per 100 000; from 9.2 to 55.1 per 100 000).

Objectives
To describe trajectories in melanoma survivors’ adherence to monthly total skin self-examination (TSSE) over 12 months, and to investigate whether adherence trajectories can be predicted from demographic, cognitive or emotional factors at baseline.

Design
A longitudinal observational study nested within the intervention arm of the ASICA (Achieving Self-Directed Integrated Cancer Aftercare) randomised controlled trial.

Setting
Follow-up secondary care in Aberdeen and Cambridge UK.

Participants
n=104 adults (48 men/56 women; mean age 58.83 years, SD 13.47, range 28–85 years; mean Scottish Index of Multiple Deprivation score 8.03, SD 1.73, range 2–10) who had been treated for stage 0–IIC primary cutaneous melanoma in the preceding 60 months and were actively participating in the intervention arm of the ASICA trial.

Interventions
All participants were using the ASICA intervention—a tablet-based intervention designed to support monthly TSSE.

Primary and secondary outcome measures
The primary outcome was adherence to guideline recommended (monthly) TSSE over 12 months. This was determined from time-stamped TSSE data recorded by the ASICA intervention app.

Results
Latent growth mixture models identified three TSSE adherence trajectories (adherent –41%; drop-off –35%; non-adherent –24%). People who were non-adherent were less likely to intend to perform TSSE as recommended, intending to do it more frequently (OR=0.21, 95% CI 0.06 to 0.81, p=0.023) and were more depressed (OR=1.31, 95% CI 1.06 to 1.61, p=0.011) than people who were adherent. People whose adherence dropped off over time had less well-developed action plans (OR=0.78, 95% CI 0.63 to 0.96, p=0.016) and lower self-efficacy about TSSE (OR=0.92, 95% CI 0.86 to 0.99, p=0.028) than people who were adherent.

Conclusions
Adherence to monthly TSSE in people treated for melanoma can be differentiated into adherent, drop-off and non-adherent trajectories. Collecting information about intentions to engage in TSSE, depression, self-efficacy and/or action planning at outset may help to identify those who would benefit from additional intervention.

Trial registration number
ClinicalTrials.gov Registry (NCT03328247).

Objective
To evaluate the association of serum vitamin D levels and dietary intake with melanoma risk and prognostic factors.

Methods
Two independent investigators systematically searched PubMed, Embase and ISI Web of Knowledge (Thomson Scientific Technical Support, New York) databases for eligible studies published between January 1992 and September 2020 using the following combinations of search terms: (vitamin D, or 25-hydroxyvitamin D) AND (melanoma, malignant melanoma, cutaneous melanoma, or cutaneous malignant melanoma). Articles not written in English but with English titles and abstracts were also checked. We obtained the full text of all potentially eligible articles, and reference lists of all studies retrieved at the first stage were also checked to identify other eligible papers. Review articles not reporting original data were excluded, but their reference lists were inspected.

Results
Six studies including 212 723 cases reported the association between dietary intake of 25(OH) D serum levels and melanoma risk. The total relative risk for the comparison between the highest and lowest quantiles of the distribution of vitamin D intake was 1.10 (95% CI 0.96 to 1.26) with I2=56%. Another six studies including 12 297 cases evaluated the association between serum vitamin D levels and melanoma risk. The total relative risk for the comparison of serum vitamin D levels between the highest and lowest quantiles was 1.12 (95% CI 0.53 to 2.35) with I2=91%. Four studies with 2105 cases investigated the association between serum 25(OH)D (nmol/L) and Breslow thickness, three of which found an inverse association between serum 25(OH)D (nmol/L) and melanoma thickness.

Conclusions
Vitamin D intake and serum 25(OH)D levels were not closely related with melanoma risk, but an inverse association between serum 25(OH)D levels with melanoma thickness was discovered. As the positive correlation between melanoma thickness and melanoma mortality has been recognised, hence it is concluded that a moderate dietary vitamin D supplement to avoid the serum 25(OH)D deficient might be beneficial to the long-term survival of patients with melanoma.