Search Results for: Melanoma cutaneo

Fatta luce sul ruolo della proteina Spry1

Objective
Incidence and mortality are fundamental epidemiologic measures of cancer burden, yet few studies have examined individual cancers to determine how these measures correlate across place. We assessed the relationship between incidence and mortality for commonly diagnosed cancers in the USA.

Design
Population-based observational study of US counties.

Setting and participants
The Surveillance, Epidemiology and End Results (SEER) database was used to obtain incidence (2000–2016) and mortality (2002–2018) data for the 12 most commonly diagnosed non-haematologic cancers.

Outcome measures
County-level correlation between cancer incidence and mortality. Cancers were grouped into terciles based on the population-weighted correlation coefficient (r). We also examined the 10 year risk of death, both from the diagnosed cancer and other causes.

Results
County-level incidence and mortality were strongly correlated in some cancers, yet uncorrelated in others. Cancers in the high-correlation tercile (r range: 0.96 to 0.78) included lung, stomach, liver and pancreas. For patients with these cancers, the risk of death from the diagnosed cancer was >4-times the risk of death from other causes. The moderate-correlation tercile (r: 0.75 to 0.58) included cancers of the colon, bladder, kidney and uterus. There was little or no relationship between incidence and mortality for cancers in the low-correlation tercile (r: 0.33 to –0.10): melanoma, prostate, breast and thyroid. The risk of death from the diagnosed cancer for these patients was either lower or no different than their risk of death from other causes.

Conclusions
For some cancers in the USA, the fundamental epidemiologic measure of disease frequency—incidence—now has little relationship with cancer death (mortality). Low correlations are most likely explained by differences in diagnostic practice leading to variable amounts of cancer overdiagnosis between different US counties.

Introduction
The prognosis for epithelial ovarian cancer (EOC) is exceedingly poor, with patients diagnosed with stage III/IV tumours typically offered cytoreductive surgery in conjunction with chemotherapy as a standard treatment option. This approach is intended to reduce the risk of surgery and address ovarian cancers that are not amenable to surgical intervention. A promising alternative and important treatment option is neoadjuvant chemotherapy (NACT) in conjunction with interstitial tumour cytoreductive surgery. The combination of neoadjuvant immunotherapy with chemotherapy has recently demonstrated remarkable efficacy, particularly in melanoma and lung cancer, with notable pathological responses and therapeutic benefits in tumour tissue. The NeoAdjuvant chemotherapy with or without tIslelizumab followed by debulking surgery for oVarian cancEr(NAIVE) study aims to assess the clinical efficacy and safety of NACT in combination with tislelizumab (a monoclonal antibody for programmed cell death protein 1) for advanced EOC.

Methods and analysis
The NAIVE study is an investigator-initiated, prospective, single-centre, open-label, randomised controlled trial for advanced EOC with the International Federation of Gynaecology and Obstetrics (FIGO) stage IIIc with a Suidan CT score of 3 or greater or a Fagotti laparoscopic score of 8 or greater; or FIGO stage IV. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate, measured as the percentage of patients who are free of tumour progression or death for 1 year after receiving the first dose of study drug. The secondary endpoints encompassed the R0 resection rate, the clinical response rate and other relevant metrics. Enrolled patients will be randomly assigned in a 1:1 ratio to either the experimental arm, which will receive neoadjuvant platinum-based chemotherapy in combination with tislelizumab, or the control arm, which will receive neoadjuvant platinum-based chemotherapy. The study will enrol 40 patients, with enrolment scheduled to start in April 2021 and complete in April 2025, given a 1-year PFS rate of 60%. The study will provide new evidence regarding the clinical efficacy and safety of NACT in combination with tislelizumab for advanced ovarian cancer. The results will contribute to a deeper understanding of the clinical effects, safety profile and fundamental immunological processes. The findings will contribute to the growing body of evidence in support of the incorporation of immunotherapy into the treatment paradigm for ovarian cancer, thus facilitating the development of more personalised and efficacious therapeutic modalities.

Ethics and dissemination
This trial has received ethical approval from the Institutional Ethics Committee of the Second Affiliated Hospital of the Medical College of Zhejiang University. Presentations at scientific and professional meetings and publication in peer-reviewed journals will disseminate the results of the study.

Trial registration number
NCT04815408.

This cohort study evaluates the association between cutaneous melanoma tumor mutational burden and indoor tanning exposure, as well as other demographic, dermatologic, and tumor characteristics.

This cohort study examines the association between the risks of melanoma-associated death and nonmelanoma-associated death for each 0.1-mm increase in Breslow thickness from 0.1 mm to 1.0 mm in a large cohort of adults diagnosed with a first invasive primary melanoma of 1.0 mm or smaller in Australia.

Objective
This study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab or pembrolizumab) or targeted therapy consisting of BRAF/MEK inhibitors.

Design
Retrospective chart review study.

Setting
Academic medical centres, community hospitals and private practice offices.

Participants
Included patients diagnosed with melanoma with brain metastasis in the USA.

Outcome measures
The statistical analysis was descriptive in nature. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between treatments in a univariate Cox proportional hazards model.

Results
In total, 472 patients with MBM who received first-line nivolumab plus ipilimumab (n=246), anti-PD-1 monotherapy (n=112) or BRAF/MEK inhibitors (n=114) were identified. Patients receiving nivolumab plus ipilimumab, compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors, had favourable baseline prognostic factors, such as younger age, fewer or smaller brain metastases, better Eastern Cooperative Oncology Group performance status and less frequently elevated lactate dehydrogenase. Median follow-up times were 15.4 months (range 0.1 to 37.0), 13.3 months (range 0.3 to 36.6) and 13.9 months (range 1.9 to 36.5), respectively. Numerically longer OS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.47, 95% CI 0.34 to 0.67) or BRAF/MEK inhibitors (HR 0.72, 95% CI 0.50 to 1.04) and numerically longer PFS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.74, 95% CI 0.53 to 1.02) or BRAF/MEK inhibitors (HR 0.82, 95% CI 0.60 to 1.12). With nivolumab plus ipilimumab, anti-PD-1 monotherapy and BRAF/MEK inhibitors, 1-year OS rates were 79%, 60% and 72%, respectively; 1-year PFS rates were 68%, 58% and 59%.

Conclusions
In this real-world study, first-line nivolumab plus ipilimumab appeared to provide benefit versus anti-PD-1 monotherapy and BRAF/MEK inhibitors in patients with MBM, consistent with pivotal trial data. However, the observed benefit may have been due to confounding and selection bias, given that patients receiving nivolumab plus ipilimumab had favourable baseline prognostic factors compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors.

Objective
To characterise diagnostic pathways for patients with melanoma in routine practice and compare patient, disease and diagnostic interval (DI) characteristics across pathways.

Design
Descriptive cross-sectional study using administrative health data.

Setting
Population-based study in Ontario, Canada.

Participants
Patients with melanoma diagnosed from 2007 to 2019.

Main outcome measures
We used latent class cluster analysis to create clusters of patients with similar diagnostic experiences to characterise diagnostic pathways in routine practice. Indicator variables characterised the patient’s keratinocyte carcinoma and dermatologist history, presentation pattern, procedure types, number of visits and procedures, and the activity on the diagnosis date. 2 tests and Pearson residuals were used. We characterised clusters by the lengths of their DI, primary care subinterval and specialist care subinterval.

Results
There were 33 371 patients diagnosed with melanoma from 2007 to 2019. We identified four diagnostic pathways: ‘primary care only’ (n=6107), ‘referred to specialist with immediate action’ (n=8987), ‘multiple visits and procedures in specialist care’ (n=11 893) and ‘specialist care only’ (n=6384). Patient, disease and DI characteristics varied across pathways. Pathway types varied regionally. A higher proportion in the ‘primary care only’ pathway lived in rural areas whereas a higher proportion in the ‘referred to specialist for immediate action’ and the ‘specialist care only’ pathways lived in major urban centres. Across pathways, the median DI varied from 1 to 67 days, the median primary care subinterval varied from 1 to 30 days and the median specialist care subinterval varied from 1 to 25 days. Patients in the ‘primary care only’ pathway experienced the shortest DIs, and patients in the ‘multiple visits and procedures in specialist care’ pathway experienced the longest DIs.

Conclusions and relevance
We identified four melanoma diagnostic pathways. The shortest DI, the ‘primary care only’ pathway, highlights the important role of primary care and the need to reduce the wait for specialists. Diagnostic processes varied across geographical locations. Future research should address reasons for these differences, including whether they are associated with inefficient or inappropriate care.

Introduction
Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.

Methods and analysis
We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort ‘trial emulation’ study with an active comparator and new-user design. Individuals with MS aged ≥18 years will be identified using a validated algorithm. Incident users of fingolimod and active comparators (natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide) will then be identified. The outcome of interest will be skin cancer (melanoma and non-melanoma skin cancers). Survival analysis will be used to estimate HRs and corresponding 95% CIs, adjusted for potential confounders.

Ethics and dissemination
Ethics approval for this study was obtained from the University of British Columbia Clinical Research Ethics Board (H24-03199). No personal identifying information will be made available as part of this study. Findings will be disseminated through presentations and peer-reviewed publications.

Trial registration number
NCT06705608.

Ascierto, il 50% dei pazienti metastatici sopravvive a 10 anni dalla diagnosi

Introduction
The sun is one of the primary natural sources of ultraviolet radiation (UVR) and a known human carcinogen. It has been related to melanoma and several skin cancers, such as squamous cell carcinoma and basal cell carcinoma. Non-melanoma skin cancers are prevalent in South Africa, with high reported incidence rates in both genders. Due to its diversified population, South Africa experiences extreme ultraviolet index (UVI) levels, reaching 13 in the summer (a UVI of 11+ is considered extreme). Most summer workdays expose outdoor workers to repeated UVR exposure, which can lead to health risks like sunburn, premature ageing, cataracts, and an increased risk of skin cancer. This study aims to evaluate UV radiation exposure among outdoor military workers.

Methods and analysis
A cross-sectional quantitative study will occur at the Lohatla military base in Kathu, Northern Cape province of South Africa, using personal electronic dosimeters for solar UVR assessment. Additionally, a self-administered questionnaire will assist in assessing health effects and perceived exposure behaviours. The study addresses a critical public health concern, exploring significant risks associated with UVR exposure among outdoor military workers across different demographics.

Ethics and dissemination
The ethical approval for this study was obtained from the Health Sciences Research Committees of the University of Free State (UFS-HSD2023/1227/2811). The confidential data will be accessed by the named researchers and stored in secure password-protected platforms. In addition, the findings will be disseminated through high-impact publications in various formats to government departments and the broader scientific community.

New England Journal of Medicine, Volume 392, Issue 1, Page 81-82, January 2, 2025.

Introduction
A diagnosis of melanoma in situ presents negligible risk to a person’s lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients’ management choices and anxiety levels.

Methods and analysis
This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: ‘melanoma in situ’ (control), ‘low-risk melanocytic neoplasm’ (intervention 1) and ‘low-risk melanocytic neoplasm, in situ’ (intervention 2). The required sample size is 1668 people. The co-primary outcomes are (1) choice between no further surgery or further surgery to ensure clear histological margins greater than 5 mm and (2) choice between patient-initiated clinical follow-up when needed (patient-led surveillance) and regular routinely scheduled clinical follow-up (clinician-led surveillance). Secondary outcomes include diagnosis anxiety, perceived risk of invasive melanoma and of dying from melanoma and management choice anxiety (after surgery choice and follow-up choice). We will make pairwise comparisons across the three diagnostic label groups using regression models (univariable and multivariable).

Ethics and dissemination
The study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000740594). Ethics approval has been received from The University of Sydney Human Research Ethics Committee (2024/HE000019). The results of the study will be published in a peer-reviewed medical journal, and a plain language summary of the findings will be shared on the Wiser Healthcare publication page (https://www.wiserhealthcare.org.au/category/publications/).

Trial registration number
Australian New Zealand Clinical Trials Registry (ID 386943).

Several studies have highlighted the significance of targeting fat mass and obesity-associated protein (FTO) in gastrointestinal cancers including hepatocellular carcinoma (HCC) .1 The recent study from the group of Irene Oi-Lin Ng presented in Gut by Chen et al2 introduces new insights into the molecular dynamics of HCC, focusing on the pivotal role of FTO in the disease’s pathophysiology. Functioning as an eraser of N6-methyladenosine (m6A), FTO modulates RNA stability and translation. In the context of HCC, FTO’s activity leads to the stabilisation of oncogenic transcripts, thereby promoting cancer cell proliferation and survival.3 The study identifies glycoprotein non-metastatic melanoma protein B (GPNMB) as a downstream effector of FTO (figure 1). By diminishing the m6A modification on GPNMB, FTO enhances its stability, thereby protecting it from YTHDF2-mediated degradation. This stabilisation facilitates the incorporation of GPNMB into small extracellular vesicles (sEVs), which are…

Objective
Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown.

Design
The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment.

Results
FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumour-infiltrating CD8+ T cells. Furthermore, we identified GPNMB to be a downstream target of FTO, which reduced the m6A abundance of GPNMB, hence, stabilising it from degradation by YTH N 6-methyladenosine RNA binding protein F2. Of note, GPNMB was packaged into sEVs derived from HCC cells and bound to the surface receptor SDC4 of CD8+ T cells, resulting in the inhibition of CD8+ T cell activation. A potential FTO inhibitor, CS2, suppresses the oncogenic functions of HCC cells and enhances the sensitivity of anti-PD-1 and sorafenib treatment.

Conclusion
Targeting the FTO/m6A/GPNMB axis could significantly suppress tumour growth and metastasis, and enhance immune activation, highlighting the potential of targeting FTO signalling with effective inhibitors for HCC therapy.

Ascierto, +25% di sopravvivenza in forme malattia avanzate

Ascierto, ‘dai raggi solari ci si deve difendere anche in inverno’