Rise In Incidence Of Melanoma Research Articles

Melanoma Incidence and Mortality Trends in Sweden.

Over the past decades, many global regions have experienced a steady increase in the incidence of cutaneous melanoma. However, more recently, a downward trend has been observed in the younger age groups in Australia and the US. Yet, in Europe, none of the countries have reported any significant decline in melanoma incidence for any age group. To assess melanoma incidence and mortality trends in Sweden, with a focus on individuals younger than the average age of melanoma onset. This cohort study used data on the national population from the Swedish Melanoma Registry and the Swedish Cancer Registry, which cover more than 99% of all primary invasive cutaneous melanomas diagnosed in the country. All patients diagnosed from 1990 to 2022 were included. Incidence and mortality rates per 100 000 inhabitants were calculated for each year and shown as average annual rates for every 5-year period from 1990 to 2022. Joinpoint regression models were used to evaluate statistical significance of temporal trends and points of change. There were 34 800 primary invasive cutaneous melanomas (19 582 [56.3%] in females and 15 218 [43.7%] in males) reported in 33 324 individuals younger than 60 years (median [IQR] age, 48 [36-58] years) from 1990 to 2022. A consistent rise in melanoma incidence was observed among those 50 to 59 years old. The age groups from 20 to 29 years, 30 to 39 years, and 40 to 49 years showed an incidence peak in 2013 to 2015 followed by stable or significantly declining rates until 2022. In patients younger than 20 years, melanoma incidence remained low with no significant trends. There was also a significant decline in melanoma mortality among 30- to 59-year-old individuals, but not in those 60 years and older. The findings of this cohort study showed a significant recent downward trend in both melanoma incidence and melanoma mortality in the age group 30 to 49 years in Sweden. The reasons for these declines are unclear but may include UV protection, public health campaigns, changing population demographics, and the introduction of effective melanoma treatment. None of these possibilities were evaluated; further study is needed.

Abstract 7472: Melanoma-intrinsic expression of signal-regulatory protein alpha (SIRPα) confers tumor cells resistance to anti-tumor adaptive immunity

Abstract Introduction: Melanoma patient survival rates have significantly improved recently owing to the development of both targeted therapies and immunotherapies. However, there are still around 50% of patients relapse. The limited response to immunotherapies and global rise in melanoma incidence, with around 290,000 cases newly diagnosed each year, highlight the need for identifying new biomarkers, modulatory pathways, and risk factors for melanoma development. Earlier studies have characterized that aberrant expression of CD47 (a.k.a. “don’t eat me” signal) is one of the mechanisms that tumors exploit to avoid innate immune surveillance. CD47 blockade has been demonstrated to restore myeloid effector function by reinvigorating phagocytosis of tumor cells, which further enhances anti-tumor T cell responses. However, melanoma tumors are resistant to CD47 blockade. Interestingly, we and others have discovered that human and mouse melanoma cells express high levels of SIRPα, the receptor for CD47, which is typically expressed in myeloid compartments. Experimental Procedure: To investigate the role of tumor SIRPα, we designed gRNAs to CRISPR out the SIRPα N-terminal region, where it interacts with CD47, in B16 melanoma and generated SIRPα+/+ (WT) and SIRPα-/- (KO) B16 tumors. We conducted multiple in vitro and in vivo experiments to investigate whether tumor SIRPα played a role in tumor growth and modulated anti-tumor immunity. The preclinical tumor model we used is B16-F10 melanoma and the murine strains we used are the immune-competent (C57BL/6j; B6) and the immune-deficient (RAGnull) mice. For phenotypic and functional assessments, we performed analysis using flow cytometry, immunohistochemistry (IHC) and single cell RNA-sequencing (scRNA-seq) derived from live-sorted CD45+ tumor infiltrating lymphocytes (TILs) of SIRPα-WT and SIRPα-KO B16 tumors. Summary of Unpublished Data Our preliminary data in a preclinical B16-F10 melanoma model revealed that surface SIRPα expression is necessary for optimal B16-F10 melanoma growth in immune-competent mice, but not in immune-deficient RAGnull mice, suggesting a potential crosstalk between tumor SIRPα and the host adaptive immune system. Intriguingly, we found that selective SIRPα deletion in melanoma cells results in a significant increase of immune infiltrates within melanoma tumors that further suppresses tumor growth. Concluding Remarks: SIRPα is required for optimal melanoma development by suppressing anti-tumor adaptive immunity. Ethics Approval: All mice were maintained in microisolator cages and treated in accordance with the NIH and American Association of Laboratory Animal Care regulations. All mouse procedures and experiments for this study were approved by the Weill Cornell Medicine Institutional Animal Care and Use Committee. Citation Format: Chien-Huan Weng, Chana Schochet, Linda Hamadene, Shabnam Eghbali, Sébastien Monette, Levi Mangarin, Cailian Liu, Fadi Samaan, Jedd D. Wolchok, Taha Merghoub. Melanoma-intrinsic expression of signal-regulatory protein alpha (SIRPα) confers tumor cells resistance to anti-tumor adaptive immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7472.

Cutaneous melanoma: An update on pathogenesis, prevention, and treatment

AbstractAlthough the cause for the rise in melanoma incidence remains a topic of debate, its potentially aggressive nature necessitates a continual update on the pathophysiologic mechanisms of disease and current guidelines for management. Akin to other cutaneous malignancies, sun exposure remains a crucial risk factor in the development of different melanoma subtypes. There are specific non‐UV associated mutations that are commonly found in most melanomas and some nevi, such as B‐RAF V600E, that may represent an initial insult of a multistep process that eventually leads to progression of the lesion into a more aggressive phenotype. The standard of care for early melanoma management remains surgical excision with wide margins, however management changes with more advanced lesions by the addition of imaging, sentinel lymph node biopsies, genetic testing, immune, and targeted therapy. Different novel treatment regimens for advanced unresectable melanomas are being investigated with the use of targeted therapies and vaccines. Novel screening technology using artificial intelligence for detection of melanoma is currently being developed but remains in its early stages with its effectiveness being significantly lower compared to clinicians. As such, melanoma prevention and early detection through skin examinations remain crucial to avoid potentially deadly complications from more advanced lesions.

Dermoscopy Use in Primary Care: A Scoping Review

Patients in many countries with new or changing skin lesions will first consult a primary care physician, often called a general practitioner (GP). With the dramatic rise in melanoma incidence over recent decades, dermoscopy offers a tool with an evidence base supporting its use in skin lesion assessment. How GPs use dermoscopy is unclear. A scoping literature review was carried out to examine the current state of published evidence about dermoscopy use in primary care. The methodological steps taken in this review followed those developed by Arksey and O'Malley, as revised by Levac and colleagues. Four electronic databases were searched for evidence published up to January 2018 describing the use of dermoscopy in a generalist primary care setting. Seven articles were identified for analysis. All included articles have been published since 2007. Most were questionnaire studies and revealed that generally a small minority of GPs use dermoscopy, although some jurisdictions such as Australia report greater use. Dermoscopy is generally used only for the assessment of pigmented skin lesions, but is not used consistently. Several perceived barriers to dermoscopy use, including the need for training, have been reported. There is a paucity of data on dermoscopy use among GPs, and diversity in questionnaire items prevents comparison between jurisdictions. Perceived barriers to dermoscopy use require more in-depth exploration, potentially including qualitative data, to evaluate them more fully. Understanding these factors, including how GPs train in dermoscopy, will be crucial in widening dermoscopy use in primary care.

Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.

The incidence of cutaneous melanoma increased dramatically in Iceland during the last two decades of the 20th century. The aim of this study was to investigate the trend in Breslow's tumour thickness during the years 1980-2009. The population-based Icelandic Cancer Registry provided information on all cutaneous melanomas diagnosed in the country during the study period, a total of 854 cases. Incidence rates were stratified according to gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness. When stratified by gender and age, the incidence of thin (≤1.0 mm) melanomas increased dramatically in all subgroups. The increase in thin (≤1.0 mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3 in 2000-2009 and especially in young (<50 years) women or from 1.6 to 12.2 per 100,000 during the same period compared to an increase from 0.2 to 3.4 per 100,000 for young (<50 years) men (P < 0.05). In intermediate thickness (1.01-4.0 mm) tumours, the incidence increased only in men over the age of 50 from 2.1 in 1980-1989 to 11.3 per 100,000 in 2000-2009 (P < 0.05). The incidence of thick melanomas (>4 mm) did not increase. The median Breslow's thickness declined from 2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in females for the same period (P < 0.001). The rise in melanoma incidence in individuals under 50 years and in women over 50 years was confined to thin tumours. However, among older males there was also an increased incidence of tumours of an intermediate thickness. This could indicate that future melanoma educational campaigns in Iceland should be directed at older individuals, and that older men may need special attention regarding suspicious nevi.

Microinvasive Melanoma

Surgical excision is the treatment of choice for primary melanomas and radiation therapy is the accepted alternative for the subset of lesions not amenable to surgery. With the recent rise in melanoma incidence, especially in the elderly, there are a growing number of cases that are neither amenable to surgery nor radiation therapy. In this article, we review pharmacotherapeutic approaches to microinvasive melanoma (invasive radial growth phase melanoma) that might be considered in such circumstances. There are no approved drugs for the treatment of primary melanoma and randomized controlled trials with 5 or more years of follow-up have not been performed. The limited studies and numerous case series in the literature on pharmacologic treatment of primary melanoma have focused on topical therapies. Accordingly, we provide a review of the potential pharmacotherapeutic agents in the treatment of microinvasive melanoma by extrapolating from the available limited literature on the use of fluorouracil, azelaic acid, retinoic acid derivatives, interferon (IFN)-α, imiquimod, and other agents for melanoma in situ, invasive melanoma, and epidermotropic melanoma metastases. Our review indicates that topical fluorouracil and tretinoin are not effective as single agents. The efficacy of azelaic acid, tazarotene, cidofovir, and intralesional IFN-α, interleukin-2, and IFN-β is undefined. Imiquimod is the most studied and promising agent; however, optimal dosage, therapeutic regimen, and survival rates are unknown. In the face of a growing demand for non-surgical treatments, formal clinical trials are needed to ascertain the role of pharmacotherapeutic agents in the treatment of microinvasive melanoma.

The melanoma ‘epidemic’: lessons from prostate cancer

The rise in malignant melanoma incidence has been termed "epidemic". Closer scrutiny of epidemiologic data suggests overdiagnosis as the true cause of the dramatic rise in melanoma incidence. In epidemiologic terms, "overdiagnosis" describes lesions that are histologically malignant but biologically benign. Overdiagnosis is not unique to melanoma screening but is prevalent in screening for cancers of other organs, including the thyroid and prostate glands.

The melanoma ‘epidemic’, a dermatopathologist's perspective

Over the past several decades, the rise in melanoma incidence has been termed "epidemic." However, detailed analysis of mortality data suggests that the true incidence of melanoma has not increased dramatically. Dermatopathologists, who hold a key position in the diagnosis of melanoma, should have unique insight into this quandary. Factors contributing to the apparent melanoma epidemic likely include intense screening, sampling of earlier lesions, medical-legal pressures, imperfect diagnostic methodology, and lack of a usable gold standard. Consequences of the apparent melanoma epidemic are also explored herein.

The melanoma epidemic debate: some evidence for a real phenomenon from Tuscany, Italy

Our objective was to evaluate whether or not recent mortality data for the region of Tuscany confirm the hypothesis that an epidemic in the incidence of melanoma is an apparent phenomenon reflecting an overdiagnosis of indolent cases. We considered 1755 melanoma deaths in Tuscany in the period 1987-2003, and 2644 incidence cases of melanoma diagnosed in 1985-2003 in a subset of the same population. We calculated annual mortality and incidence trends using the National Cancer Institute's Joinpoint Program (version 2.6). We observed an increasing mortality from melanoma from 1987 to 2003 in both sexes, but mainly in women (estimated annual percentage changes=2.25; P<0.05). We also observed a statistically significant rise in melanoma incidence in both sexes, mainly of thin lesions. Furthermore, we observed an increase in thick lesions, especially in females (estimated annual percentage changes=2.9; P<0.05), and for lesions without Breslow definition. In conclusion, the rise in melanoma mortality and incidence, especially of thick lesions, suggests that the observed growth in melanoma incidence is not wholly apparent.

Non-Hodgkin's Lymphoma and Sunlight

Incidence and mortality rates for nonHodgkin's lymphoma (NHL) continue to rise dramatically throughout the world (7,2). Changes in diagnostic practices and in levels of exposure to the established risk factors for NHL (including genetic predisposition, immunosuppression, infection with human immunodeficiency virus [HIV], and various occupational exposures) cannot account for the long-term, worldwide increases (3). On the basis of epidemiologic and experimental observations, some investigators (4,5) recently suggested that sunlight may contribute to the development of NHL and its upward trend. In particular, the rise in NHL incidence parallels the global rise in melanoma incidence (6), patients with NHL are at an elevated risk of developing melanoma (7-10), and experimental data show immunosuppressive effects of UV radiation that may predispose to melanoma or other cancers (//). The hypothesis that sunlight exposure may affect NHL risk (4Jj,10) prompted us to review the geographic patterns of mortality rates in the United States for the following three decades: 1950-1959, 1960-1969, and 1970-1980 (12). In white men and white women, NHL mortality was consistently lower in the southern half of the United States, particularly during the earliest period. In contrast, mortality from melanoma of the skin and nonmelanoma skin cancer A. White men

Barriers to effective skin cancer detection

In response to the dramatic rise in melanoma incidence, numerous health care specialists have encouraged primary care providers to increase skin cancer detection efforts. Although primary care providers currently find more melanomas than do dermatologists, many detection opportunities are missed. In addition, primary care providers occasionally incorrectly reassure patients about specific lesions. Nevertheless, there is little evidence that efforts to detect skin cancer are growing. This paper discusses barriers to skin cancer detection and potential ways to increase screening. Methods involve the review of the medical literature and the author's synthesis of this information. The principle barriers to skin cancer detection are that it is a low priority in primary care, that the majority of exams do not result in significant findings, and that many providers lack expertise to adequately identify high risk lesions. Lack of reimbursement for preventive care, inadequate time for complete skin exams, and distraction by other health problems also play a role in limiting skin cancer detection efforts. Relying on primary care-based skin cancer detection as the only means to increase skin cancer identification is an unwise policy. Approaches that may be able to increase skin cancer prevention and detection include increased (1) collaboration between skin cancer specialists and experts in primary care, (2) focus on providers of pediatric care, (3) advocacy for reimbursement of preventive health care, (4) educational efforts for the public to request skin exams, and (5) education directed to providers in high risk areas.

Developing and evaluating a cancer prevention teaching module for secondary education: Project SAFETY (Sun Awareness for Educating Today's Youth).

The University of Texas M.D. Anderson Cancer Center (UTMDACC) is concerned with the meteoric rise in incidence of melanoma. As few as three episodes of blistering sunburns before age 20 increases two to three times an individual's risk for developing this malignancy. These statistics have compelled the UTMDACC to develop a comprehensive prevention program on skin cancer directed specifically to our youth. It is designed to be incorporated into the high school biology curriculum and is composed of three 50-minute teaching programs bound together with common themes, visuals, and treatment styles. The incorporation of prevention practices limiting damaging exposure to ultraviolet irradiation would significantly impact the future incidence of skin cancer in these individuals.