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Background Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population. Materials and Methods This French multicenter real-world study was conducted between September 2020 and July 2023. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (version 1.1). Secondary variables were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Results Of the 67 patients included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV-M1c or M1d disease. The overall ORR was 28.4% (95% CI, 18%-41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. Median DOR was 3.1 (interquartile range, 1.3-4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5-3.7) and 9.8 (95% CI, 5.6-13.9) months, respectively. Grades 3-5 TRAEs occurred in 16 (24%) patients; common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). No treatment-related deaths occurred. Conclusion Our real-world study demonstrates an interesting response rate and acceptable safety profile in a population with poor prognostic factors. Our data support this treatment option for refractory melanoma, as it is not approved by the Food and Drug Administration or European Medicines Agency, and highlight the need for new strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic ablative radiation (SAbR) is a focused, high-dose radiation technique used to treat cancers that have spread to the adrenal glands. One of the feared consequences of this therapy is causing adrenal insufficiency in patients, which is a lack of adrenal function; however, the rates and severity at which this occurs in patients are still poorly studied. We studied patients with 66 treated adrenal glands using SAbR, which demonstrated that this technique was effective at controlling cancer sites with a control rate of 75% at 1 year. The risk of patients developing adrenal insufficiency in the entire cohort was significant at 14%, with a median time of 4.3 months. There was a higher risk in patients who had both adrenal glands treated with SAbR, or who had received a prior surgical removal of their other adrenal gland prior to SAbR therapy, with 44% of these patients developing adrenal insufficiency. Background: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. Methods: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. Results: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7–20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. Conclusions: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to report clinical outcomes of patients with vaginal melanoma (VaM) or vulvar melanoma (VuM) who were treated with immune checkpoint inhibitors (ICI) and discuss the development of immune‐related adverse events (irAE). Materials and Methods. This is a retrospective case series of patients diagnosed with VaM or VuM between July 2011 and September 2022 at the University of Virginia, Emily Couric Clinical Cancer Center. Patient demographics, disease characteristics, treatment outcomes, and adverse events were abstracted. The primary outcome was incidence of irAE. Results. Eight patients were included in this study, four with VaM and four with VuM. Most (n = 6) had local or regional disease at first presentation, and 25% (n = 2) presented with distant metastasis. All patients received a CTLA‐4 inhibitor and 75% (n = 6) received PD‐1 inhibitor alone or in combination with a CTLA‐4 inhibitor. Most (75%, n = 6) patients experienced irAE. Of those who had irAE, 83% (n = 5) required therapy interruption or discontinuation. Most (66%, n = 4) underwent ICI rechallenge of which 75% (n = 3) experienced subsequent irAE. Of all patients in the series, 75% of patients (n = 6) had partial or complete response to ICI. Conclusion. This series is the first to detail incidence of irAEs and ICI rechallenges in vulvovaginal melanoma. Our findings indicate that while ICIs are effective, their use is associated with significant irAE development. Rechallenge of ICI after irAE is feasible but associated with risk of recurrent/new irAE. Further studies are needed to better quantify this risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with stage IIB and IIC melanoma are considered to have high-risk localized disease and, in some cases, demonstrate worse recurrence-free and overall survival than patients with stage IIIA and even IIIB disease. The mainstay of treatment for patients with high-risk clinical stage II melanoma is surgical resection of the primary tumor and sentinel lymph node biopsy (SLNB), which confers accurate pathologic staging and prognostication for further treatment decisions. Building on the success of adjuvant therapy for stage III melanoma, the KEYNOTE-716 and CheckMate 76K trials found improved recurrence-free survival for patients with high-risk stage II melanoma with adjuvant pembrolizumab and nivolumab, respectively, after complete resection with SLNB. Given these findings, the National Comprehensive Cancer Network now recommends discussing adjuvant pembrolizumab or nivolumab with patients with high-risk stage IIB/C melanoma, weighing the risks of recurrence against the risks of treatment-related adverse events when making the decision regarding adjuvant therapy. Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases (BMs), the most common type of cerebral tumor, are primarily associated with lung cancer, breast cancer, and melanoma. Patients typically present to the emergency department (ED) with insidious symptoms such as headaches, focal neurological deficits, seizures, and signs of increased intracranial pressure. Key symptomatic treatment in the ED includes corticosteroids to manage peritumoral edema, and carefully selected antiepileptic medications for tumor-related epileptic conditions. After stabilization, the treatment philosophy for BMs should prioritize effective yet minimally toxic options to maximize quality of life. Surgery is recommended for accessible BMs in patients with good performance status. Radiation therapy and systemic treatments, including chemotherapy, targeted therapy, and immunotherapy, are available options for managing disease progression. Given that over half of patients with BMs in the ED are admitted, a better understanding of avoidable hospitalizations is essential to differentiate those who can be safely discharged from those needing observation or hospitalization. Brain metastases (BMs) are the most prevalent type of cerebral tumor, significantly affecting survival. In adults, lung cancer, breast cancer, and melanoma are the primary cancers associated with BMs. Symptoms often result from brain compression, and patients may present to the emergency department (ED) with life-threatening conditions. The goal of treatment of BMs is to maximize survival and quality of life by choosing the least toxic therapy. Surgical resection followed by cavity radiation or definitive stereotactic radiosurgery remains the standard approach, depending on the patient's condition. Conversely, whole brain radiation therapy is becoming more limited to cases with multiple inoperable BMs and is less frequently used for postoperative control. BMs often signal advanced systemic disease, and patients usually present to the ED with poorly controlled symptoms, justifying hospitalization. Over half of patients with BMs in the ED are admitted, making effective ED-based management a challenge. This article reviews the epidemiology, clinical manifestations, and current treatment options of patients with BMs. Additionally, it provides an overview of ED management and highlights the challenges faced in this setting. An improved understanding of the reasons for potentially avoidable hospitalizations in cancer patients with BMs is needed and could help emergency physicians distinguish patients who can be safely discharged from those who require observation or hospitalization. [ABSTRACT FROM AUTHOR]

Introduction: Melanoma, a deadly form of skin cancer, has witnessed a notable increase in incidence over the past decades. Despite advancements in treatment, it remains a significant cause of cancer mortality. Understanding demographic trends and variations in melanoma mortality is crucial for addressing disparities and implementing effective interventions. Methods: Using the Centers for Disease Control Wide Ranging Online Data for Epidemiologic Research (CDC WONDER) database, we analyzed melanoma mortality data in the United States from 1999 to 2020. Data were stratified by demographic and regional variables, and age-adjusted mortality rates were calculated. Descriptive analysis was performed and Joinpoint regression analysis was employed to identify temporal trends. Results: Between 1999 and 2020, there were 184,416 melanoma-related deaths in the United States Overall, the age-adjusted mortality rate declined from 2.7 to 2.0 per 100,000 people at a rate of -1.3% annually, with significant variations across demographic groups and regions. Men, non-Hispanic White individuals, and those aged > 65 experienced higher mortality rates. Non-Hispanic White individuals noted the steepest decrease in AAMR after 2013 at a rate of -6.1% annually. Disparities were seen by geographic density, with rural populations exhibiting higher mortality compared to their urban and suburban counterparts. Conclusion: The study highlights a significant reduction in melanoma mortality in the U.S. since 2013, potentially attributed to advancements in diagnostic techniques such as dermoscopy and the introduction of immune checkpoint inhibitors. Disparities persist, particularly among rural populations. Targeted interventions focusing on increased screening and education are warranted to further mitigate melanoma mortality and address demographic disparities. [ABSTRACT FROM AUTHOR]

Melanoma is the fifth most common cancer in the United States. Conventional drug discovery methods are inherently time-consuming and costly, which imposes significant limitations. However, the advent of Artificial Intelligence (AI) has opened up new possibilities for simulating and evaluating numerous drug candidates, thereby mitigating the requisite time and resources. In this context, normalizing flow models by employing machine learning techniques to create new molecular structures holds promise for accelerating the discovery of effective anticancer therapies. This manuscript introduces TumFlow, a novel AI model designed to generate new molecular entities with potential therapeutic value in cancer treatment. It has been trained on the NCI-60 dataset, encompassing thousands of molecules tested across 60 tumour cell lines, with an emphasis on the melanoma SK-MEL-28 cell line. The model successfully generated new molecules with predicted improved efficacy in inhibiting tumour growth while being synthetically feasible. This represents a significant advancement over conventional generative models, which often produce molecules that are challenging or impossible to synthesize. Furthermore, TumFlow has also been utilized to optimize molecules known for their efficacy in clinical melanoma treatments. This led to the creation of novel molecules with a predicted enhanced likelihood of effectiveness against melanoma, currently undocumented on PubChem. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited. Objective: To define the prevalence and comorbidity associations of HS. Methods: This was a cross-sectional study of EPICTM Cosmos© examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations. Results: All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98–28.23], Down syndrome (OR 11.31; CI 10.93–11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09–11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26–6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29–2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86–3.08) and basal cell carcinoma (OR 2.69; CI 2.15–3.36) were identified. Limitations: International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy. Conclusion: This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS. [ABSTRACT FROM AUTHOR]

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four‐fold to five‐fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South‐Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics‐based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinicians currently estimate the risk of a patient's melanoma returning or spreading using tumor thickness and other characteristics. Most patients are diagnosed with stage I disease and are considered to have a low risk of a poor outcome, but they account for the largest number of melanoma deaths each year. The 31-gene expression profile test (31-GEP) looks at the molecular biology of the tumor to determine a patient's risk of cancer returning or spreading. In this study, the 31-GEP was better at predicting cancer progression than current melanoma staging. The 31-GEP can help doctors personalize care and make better treatment and management plans for patients. Background: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. Methods: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013–2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. Results: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)—better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). Conclusions: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans. [ABSTRACT FROM AUTHOR]

Background: Histopathologic characteristics (HC) are a mainstay in melanoma prognosis; gene expression profiling (GEP) has emerged as a potential additional independent value. Objective: To elucidate HC predictive of groups obtained via GEP of malignant melanoma. Methods: A retrospective study analyzing HC of 265 melanomas submitted for GEP over the course of 8 years. GEP was conducted as a part of regular clinicopathologic workup through Castle Biosciences Decision Dx®. Results: Of the 265 cases, the major HC found to have an association with reported gene expression profiles were melanoma histology subtype, depth of invasion, and presence of ulcer. Limitations: This study is limited by its cross-sectional nature. Causation and long-term related outcomes of the use of GEP versus American Joint Committee on Cancer histopathologic staging cannot be ascertained by this design. Conclusions: An association, but no definitive prediction, exists between histopathologic categories of depth of invasion, melanoma subtype, and presence or absence of ulcer and gene expression profiles. GEP adds valuable data to the evaluation of malignant melanomas that cannot be definitively predicted by conventional models. The findings add to needed groundwork for comparison of traditional markers and molecular genotyping and begins to build a robust predictive model for better outcomes in patients with malignant melanoma. [ABSTRACT FROM AUTHOR]

A choroidal nevus is a common intraocular tumor in the United States, found in approximately 5% of Caucasian adults. The three main risks of melanocytic choroidal nevus include vision loss from a subfoveal nevus, development of subretinal fluid, and transformation of nevus into melanoma, a malignant counterpart. We explore clinical risk factors that predict benign melanocytic choroidal nevus transformation into a malignant choroidal melanoma. Based on a large analysis of 2,355 cases that were monitored longitudinally using multimodal imaging, the most recent list of clinical features includes tumor Thickness greater than 2 mm on ultrasonography, subretinal Fluid on optical coherence tomography, Symptomatic vision loss 20/50 or worse, Orange pigment on fundus autofluorescence, Melanoma hollow on ultrasonography, and DIaMeter greater than 5 mm on fundus photography. These factors are remembered with a mnemonic of the capital letters TFSOM-DIM for "To Find Small Ocular Melanoma Doing Imaging." Analysis of these factors demonstrated a Kaplan-Meier mean five-year risk of 1% with no risk factors, 11% with any one factor, 22% with any two factors, 34% with any three factors, 51% with any four factors, and 55% with any five factors. There was no patient with six risk factors. Of those with combinations of four risk factors, six of 15 combinations yielded a 70%-100% rate of transformation; of those with combinations of five risk factors, two of five combinations yielded a 70%-100% rate of transformation. Choroidal nevus carries a risk for evolving into melanoma, and understanding of clinical and imaging features predictive of this outcome is highly important. [ABSTRACT FROM AUTHOR]

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population‐based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015–2019 by 0.6%–1% annually for breast, pancreas, and uterine corpus cancers and by 2%–3% annually for prostate, liver (female), kidney, and human papillomavirus‐associated oral cancers and for melanoma. Incidence rates also increased by 1%–2% annually for cervical (ages 30–44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth‐leading cause of cancer death in both men and women younger than 50 years in the late‐1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two‐fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals. [ABSTRACT FROM AUTHOR]

Pediatric melanoma is the most commonly diagnosed skin cancer in children, with the annual incidence recently increasing by an average of 2% each year. Ultraviolet (UV) radiation from excessive sun exposure is an important carcinogenic risk factor, with penetration varying greatly throughout the country. Consequently, an individual's geographic location may play a role in how much exposure to high UV index rays they receive throughout their lifetime. The objective of this study was to use the surveillance, epidemiology, and end results SEER database to study geographic trends in incidence, staging, and mortality of pediatric melanoma between 2009 and 2019 and determine their relation to UV index in the United States. A retrospective analysis of pediatric patients from 0 to 19 years in the surveillance, epidemiology, and end results 22 registries incidence database (17 states) and 17 registries incidence-based mortality database (12 states) was conducted from 2009 to 2019 based on a diagnosis of melanoma of the skin using the International Classification of Childhood Cancer codes for malignant melanoma. Data regarding patient demographics and incidence, staging, and mortality per state were extracted. Incidence data were geographically mapped and mean UV index distribution from www.epa.gov was superimposed. Incidence of pediatric melanoma was stratified regionally, with a total of 1665 new cases from 2009 to 2019. The Northeast had 393 new cases, with 244 (62.1%) localized cases, 55 (14.0%) lymph node-invasive and metastatic (advanced) cases, and 6/146 (4.1%) cases of mortality. The Midwest had 209 new cases, with 123 (58.9%) localized cases, 29 (13.9%) advanced cases, and 1/57 (1.8%) case of mortality. The South had 487 new cases, with 224 (46.0%) localized cases, 104 (21.4%) advanced cases, and 8/232 (3.4%) cases of mortality. The West had 576 new cases, with 364 (63.2%) localized cases, 82 (14.2%) advanced cases, and 23/551 (4.2%) cases of mortality. Mean UV index was 4.4 in the Northeast, 4.8 in the Midwest, 7.3 in the South, and 5.5 in the West from 2006 to 2020. The regional difference in incidence was not statistically significant. There was a statistically significant increased number of advanced cases in the South as compared to the Northeast (P = 0.005), West (P = 0.002), and Midwest (P = 0.02), with a significant correlation coefficient of 0.7204 between advanced cases and mean UV index in the South. There is a statistically significant increased incidence of lymph node-invasive and metastatic pediatric melanoma cases in the South as compared to the West, Northeast, and Midwest regions of the United States. There is also a significant correlation between the incidence of lymph node-invasive and metastatic pediatric melanoma cases and UV index. In the pediatric population, there is no statistically significant association between total incidence and mortality of melanoma and geographic region. There is an increased prevalence of pediatric melanoma seen in White and female patients. This suggests that an individual's geographic location in the United States during childhood may play a role in their likelihood of malignant melanoma development, advanced-stage melanoma development, and mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Melanoma is a skin tumor with a high mortality rate, and early diagnosis and effective treatment are the key to reduce its mortality rate. Therefore, more and more attention has been paid for biomarker identification for early diagnosis, prognosis prediction and prognosis evaluation of melanoma. However, there is still a lack of a report that comprehensively and objectively evaluates the research status of melanoma biomarkers. Therefore, this study aims to intuitively analyze the research status and trend of melanoma biomarkers through the methods of bibliometrics and knowledge graph. Objective: This study uses bibliometrics to analyze research in biomarkers in melanoma, summarize the field's history and current status of research, and predict future research directions. Method: Articles and Reviews related to melanoma biomarkers were retrieved by using Web of Science core collection subject search. Bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer and Bibliometrix (R-Tool of R-Studio). Result: A total of 5584 documents from 2004 to 2022 were included in the bibliometric analysis. The results show that the number of publications and the frequency of citations in this field are increasing year by year, and the frequency of citations has increased rapidly after 2018. The United States is the most productive and influential country in this field, with the largest number of publications and institutions with high citation frequency. Caroline Robert, F. Stephen Hodi, Suzanne L. Topalian and others are authoritative authors in this field, and The New England Journal of Medicine, Journal of Clinical Oncology and Clinical Cancer Research are the most authoritative journals in this field. Biomarkers related to the diagnosis, treatment and prognosis of melanoma are hot topics and cutting-edge hotspots in this field. Conclusion: For the first time, this study used the bibliometric method to visualize the research in the field of melanoma biomarkers, revealing the trends and frontiers of melanoma biomarkers research, which provides a useful reference for scholars to find key research issues and partners. [ABSTRACT FROM AUTHOR]

Melanoma is the fifth most common cancer in the United States and the deadliest of all skin cancers. Even with recent advancements in treatment, there is still a 13% two-year recurrence rate, with approximately 30% of recurrences being distant metastases. Identifying patients at high risk for recurrence or advanced disease is critical for optimal clinical decision-making. Currently, there is substantial variability in the selection of screening tests and imaging, with most modalities characterized by relatively low accuracy. In the current study, we built upon a preliminary examination of differential scanning calorimetry (DSC) in the melanoma setting to examine its utility for diagnostic and prognostic assessment. Using regression analysis, we found that selected DSC profile (thermogram) parameters were useful for differentiation between melanoma patients and healthy controls, with more complex models distinguishing melanoma patients with no evidence of disease from patients with active disease. Thermogram features contributing to the third principal component (PC3) were useful for differentiation between controls and melanoma patients, and Cox proportional hazards regression analysis indicated that PC3 was useful for predicting the overall survival of active melanoma patients. With the further development and optimization of the classification method, DSC could complement current diagnostic strategies to improve screening, diagnosis, and prognosis of melanoma patients. [ABSTRACT FROM AUTHOR]

Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment. [ABSTRACT FROM AUTHOR]

The most prevalent modifiable risk factor for skin cancer is cumulative lifetime exposure to ultraviolet (UV) radiation, supporting the development of interventions promoting the early adoption of sun‐protection behaviors. This systematic review summarizes behavioral interventions designed to promote sun‐protection behaviors and reduce harmful UV exposure among U.S. adolescents. Ten studies describing 15 intervention arms were ultimately included in this review and comprised seven cross‐sectional studies, a cohort study, a quasi‐experimental study, and a randomized controlled trial. Most interventions included in this review were effective in increasing awareness of skin cancer and knowledge of the risk factors for skin cancer, but knowledge did not correlate with self‐reported frequency of sun‐protection behaviors in this population. [ABSTRACT FROM AUTHOR]

Research on mortality outcomes and non-cancer-related causes of death in patients with cutaneous melanoma (CM) remains limited. This study aimed to identify the prevalence of non-cancer-related deaths following CM diagnosis. The data of 224,624 patients diagnosed with malignant CM in the United States between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We stratified our cohort based on their melanoma stage at diagnosis and further calculated standardized mortality ratios (SMRs) for each cause of death, comparing their relative risk to that of the general US population. The total number of fatalities among melanoma patients was 60,110, representing 26.8% of the total cases. The percentage of deaths is directly proportional to the disease stage, reaching 80% in distant melanoma. The highest fatalities among the localized melanoma group (25,332; 60.5%) occurred from non-cancer causes, followed by melanoma-attributable deaths (10,817; 25.8%). Conversely, melanoma is the leading cause of death in regional and distant melanoma cohorts. Cardiovascular and cerebrovascular diseases were the most prevalent non-cancer causes of death among the three disease-stage cohorts. Compared to the general population, we did not observe an increased risk of death due to non-cancer causes in the localized CM cohort, while patients diagnosed with regional and distant CMs had a statistically significant higher risk of death from all the reported major causes of death. [ABSTRACT FROM AUTHOR]

Background: Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. Methods: A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. Results: The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [95% CI: (7.58, 12.07)]. Conclusions: Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk. [ABSTRACT FROM AUTHOR]

Background: Primary malignant melanomas of the Gastrointestinal mucosa are uncommon. Most cases of gastrointestinal (GI) melanomas are secondary, arising from metastasis at distant sites. The purpose of this study is to assess to what extent the interaction between independent prognostic factors (age and tumor site) of primary GI melanoma influence survival. Furthermore, we also aimed to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with primary GI melanoma in the past decade. Methods: A total of 399 patients diagnosed with primary GI melanoma, between 2008 and 2017, were enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of primary GI melanoma. Variables with a p value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model (model 1) to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Furthermore, we analyzed the effect of the interaction between age and primary location on mortality (model 2). Results: Multivariate cox proportional hazard regression analyses revealed higher OM in age group 80+ (HR = 5.653, 95% CI 2.212–14.445, p = 0), stomach location of the tumor (HR = 2.821, 95% CI 1.265–6.292, p = 0.011), regional lymph node involvement only (HR = 1.664, 95% CI 1.051–2.635, p < 0.05), regional involvement by both direct extension and lymph node involvement (HR = 1.755, 95% CI 1.047–2.943, p < 0.05) and distant metastases (HR = 4.491, 95% CI 3.115–6.476, p = 0), whereas the lowest OM was observed in patients with small intestine melanoma (HR = 0.383, 95% CI 0.173–0.846, p < 0.05). Multivariate cox proportional hazard regression analyses of CSM also revealed higher mortality of the same groups and lower CSM in small intestine and colon melanoma excluding the rectum. For model 2, considering the interaction between age and primary site on mortality, higher OM was found in age group 80+, followed by age group 40–59 then age group 60–79, regional lymph node involvement only, regional involvement by both direct extension and lymph node involvement and distant metastases. The small intestine had a lower OM. The rectum as primary location and the age range 40–59 interacted to lower the OM (HR = 0.14, 95% CI 0.02–0.89, p = 0.038). Age and primary gastric location did not interact to affect the OM. For the CSM, taking into account the interaction between age and the primary location, higher mortality was found in the same groups and the colon location. The primary colon location also interacted with the age group 40–59 to increase the CSM (HR = 1.38 × 109, 95% CI 7.80 × 107–2.45 × 1010, p = 0). Conclusions: In this United States population-based retrospective cohort study using the SEER database, we found that only the age range 40–59 interacted with the rectum and colon to lower and increase mortality respectively. Primary gastric location, which was the single most important location to affect mortality, did not interact with any age range to influence mortality. With those results, we hope to shed some light on this rare pathology with a very dismal prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: While surgery remains the main treatment modality for non-melanoma skin cancer (NMSC), radiotherapy still plays a major role in the treatment algorithm, even with the emergence of immunotherapy and the revolution it is causing in treatment paradigms. The aim of our review is to describe the role of radiotherapy in the definitive and adjuvant setting for NMSC. We also aim to describe the role of radiotherapy combined with immunotherapy in these cases. Non-melanoma skin cancer (NMSC) is the most common malignancy in the United States. While surgery is considered as the main treatment modality for both cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC), radiotherapy plays an important role in the treatment of NMSC, both in the adjuvant setting for cases considered high-risk for recurrence, and in the definitive setting, when surgery is not feasible or desired by the patient. The last years have seen the emergence of immunotherapy treatment for cases of advanced cSCC in the palliative, and possibly neoadjuvant settings, making the treatment paradigm more complex. In this review, we attempt to describe the different radiation modalities available for the treatment of NMSC, the indications for adjuvant post-operative treatment with radiotherapy for cSCC, the role of radiotherapy in elective neck treatment, and the efficacy, safety, and toxicity profile of this treatment in these different settings. Furthermore, we aim to describe the efficacy of radiotherapy combined with immunotherapy as a promising horizon for treating advanced cSCC. We also aim to describe the ongoing clinical studies that attempt to examine future directions for the role of radiation treatment in NMSC. [ABSTRACT FROM AUTHOR]

With the incidence of skin cancer increasing in the United States, the role of dental providers in noting suspicious skin lesions as well as advising patients in proper sun-protective strategies is more important than ever. However, the public conversation about proper sun protection is often laden with misunderstandings and pervasive myths. This article reviews the most common types of skin cancer, elucidates the differences among the types of UV radiation, and offers updated recommendations for proper sunscreen use along with adjunctive sun-protective strategies. [ABSTRACT FROM AUTHOR]

Background: Skin cancer is the most common type of cancer in the United States. Melanoma skin cancer is the deadliest form of skin cancer. In the United States, the rates of melanoma skin cancer continue to rise more than any other type of cancer. Local Problem: Nurse practitioners play an important role in early detection of skin cancer; however, minimal time is spent on dermatology training in current nurse practitioner programs to sufficiently prepare nurse practitioners to identify melanoma skin cancer. Early detection of melanoma skin cancer leads to decreased mortality. Methodology: There were approximately 75 family nurse practitioners eligible to participate. The potential participants were asked to complete the online demographic survey and a pretest questionnaire. After intervention, the participants were asked to complete a posttest questionnaire. Intervention: A web-based educational tool regarding identification of melanoma skin cancer was developed. The family nurse practitioners viewed the web-based educational module regarding melanoma skin cancer. Results: A comparison of pretest and posttest means from the questionnaire was analyzed using a t test. Thirty-three family nurse practitioners showed statistically significant improvements in knowledge after the educational intervention. In addition, confidence increased in their ability to detect melanoma skin cancer. Conclusions: This project has shown that a web-based educational module can improve family nurse practitioners' ability and confidence to detect melanoma skin cancer. This educational module was statistically effective and provides an educational framework that can be adopted by other healthcare organizations to improve nurse practitioner knowledge surrounding melanoma detection. [ABSTRACT FROM AUTHOR]

Many patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed. Using prospectively-collected whole-tissue sections, we assessed in consecutive stage I–IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification. Seven-marker signature testing designated 25.1% of patients (110/439) as high-risk (stage IA, 13.3% [43/323], IB, 53.2% [42/79], and IIA, 67.6% [25/37]). A Kaplan–Meier analysis demonstrated high-risk patients to have significantly worse DFS, MSS and OS versus low-risk counterparts (P < 0.001). In multivariable Cox regression modelling also including key clinicopathological/demographic factors, 7-marker signature data independently prognosticated the studied end-points. Models with the 7-marker signature risk category plus clinicopathological/demographic covariates substantially outperformed models with clinicopathological/demographic variables alone in predicting all studied outcomes (areas under the receiver operator characteristic curve 74.1% versus 68.4% for DFS, 81.5% versus 71.2% for MSS, 80.9% versus 73.0% for OS; absolute differences 5.7%, 10.3% and 7.9%, respectively, favouring 7-marker signature risk category-containing models). In patients with AJCC early-stage disease, the 7-marker signature reliably prognosticates melanoma-related outcomes, independent of AJCC classification, and provides a valuable complement to clinicopathological/demographic factors. • American Joint Committee on Cancer v8 early stage I-IIA melanoma includes many cases with an unfavourable course. • 7-biomarker IHC signature's ability to find at-risk stage I–IIA patients was studied. • Samples were prospectively collected from 439 consecutive stage I–IIA patients. • Results were significantly worse in 7-marker signature high-risk versus low-risk groups. • 7-marker signature high-risk class captured most recurrences and deaths from melanoma. [ABSTRACT FROM AUTHOR]

Melanoma is the fifth most common cancer diagnosed in the United States, representing 5.6% of all new cancer cases. There are conflicting reports correlating a relationship between primarily outdoor occupations, associated with increased exposure to direct sunlight, and the incidence of cutaneous melanoma. Our objective was to outline and critically evaluate the relevant literature related to chronic occupational exposure to sunlight and risk of developing cutaneous melanoma. The study protocol for this systematic review was submitted to the International Prospective Register of Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. For each relevant study included, the following information was extracted: author names, publication year, study name, study design, age, exposure assessment, outcome, comparison, number of cases, case ascertainment, and descriptive and adjusted statistics. Study quality and evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluations model. The initial database search yielded 1629 articles for review and following full-text screening, a total of 14 articles were included for final analysis. Of the studies included, seven articles were retrospective case control and seven were cohort studies. The studies did not report any differences in the likelihood of cutaneous melanoma development based upon membership in the outdoor versus indoor occupation groups included in each study. Overall, the articles included in this systematic review did not report an increased risk of developing cutaneous melanoma among individuals with outdoor occupations. Further investigation is required to determine if other occupational or life-style–related risk factors exist, to help support the development of individualized skin screening recommendations and improve the early detection of melanoma in all populations. [ABSTRACT FROM AUTHOR]

Skin cancer is one of the most prevalent cancers in the Caucasian population. In the United States, it is estimated that at least one in five people will develop skin cancer in their lifetime, leading to significant morbidity and a healthcare burden. Skin cancer mainly arises from cells in the epidermal layer of the skin, where oxygen is scarce. There are three main types of skin cancer: malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Accumulating evidence has revealed a critical role for hypoxia in the development and progression of these dermatologic malignancies. In this review, we discuss the role of hypoxia in treating and reconstructing skin cancers. We will summarize the molecular basis of hypoxia signaling pathways in relation to the major genetic variations of skin cancer. [ABSTRACT FROM AUTHOR]

Skin cancer, including melanoma, is the most common cancer worldwide and a significant public health concern. A significant risk factor for melanoma is through increased exposure to ultraviolet (UV) radiation through the use of indoor tanning beds. Although rates of indoor tanning bed use have decreased in recent years, young adults, particularly White, college-age women, comprise the majority of indoor tanning bed users in the United States. The purpose of this cross-sectional study was to explore and explain the initiation and sustenance of indoor tanning cessation among college students using the multi-theory model (MTM) of health behavior change. Data were collected from 254 college students who reported current indoor tanning use using a validated 46-item survey to assess demographics and the MTM constructs. Data were analyzed using multiple linear regression to determine the ability of the MTM constructs to predict the initiation and sustenance of indoor tanning cessation. For initiation of indoor tanning cessation, participatory dialogue: advantages (B = 0.038, p = 0.001), behavioral confidence (B = 0.129, p < 0.001) and changes in the physical environment (B = 0.088, p < 0.001) were significantly associated with indoor tanning cessation following covariate adjustment. For sustenance, only emotional transformation (B = 0.140, p < 0.001) demonstrated a significant relationship with indoor tanning cessation, following adjustment. Findings from this study demonstrate the utility of the MTM in explaining indoor tanning cessation and designing intervention strategies and clinical recommendations to encourage indoor tanning cessation among college students. [ABSTRACT FROM AUTHOR]

Purpose: Melanoma incidence is higher in rural than in urban areas in the United States, possibly due to greater incidental sun exposures from rural outdoor‐focused lifestyles and occupational patterns. Our aim was to compare activities at the time of a sunburn between rural and urban residents. Methods: Utilizing the nationally representative 2019 cross‐sectional Health Information National Trends Survey (HINTS), we report odds ratios (OR) and confidence intervals (CI) from logistic regression models comparing self‐reported activities at most recent sunburn among rural versus urban adults. Findings: About one‐third of participants (37.2%) reported a sunburn in the past year, higher in urban (38.0%) than in rural populations (32.5%). At the time of most recent sunburn, swimming (36.6%) and working outside a home (29.4%) were the most commonly reported activities. Working on a job (30.4% vs 10.4%; OR: 3.30, 95% CI: 1.33, 8.20) or outside the house (38.7% vs 28.1%; OR: 1.86, 95% CI: 1.03, 3.33) were more common, while exercising or sunbathing were less common, among rural compared to urban participants. Conclusions: Incidental sun exposures during outdoor‐focused rural occupations and work outside the house may be critical skin cancer prevention targets in rural populations; outdoor exercise and sunbathing may be more important in urban populations; incidental exposures while swimming may be important in both populations. [ABSTRACT FROM AUTHOR]

Purpose: We report the prevalence and economic cost of skin cancer treatment compared to other cancers overall in the USA from 2012 to 2018. Methods: Using the Medical Expenditure Panel Survey full-year consolidated data files and associated medical conditions and medical events files, we estimate the prevalence, total costs, and per-person costs of treatment for melanoma and non-melanoma skin cancer among adults aged ≥ 18 years in the USA. To understand the changes in treatment prevalence and treatment costs of skin cancer in the context of overall cancer treatment, we also estimate the prevalence, total costs, and per-person costs of treatment for non-skin cancer among US adults. Results: During 2012–15 and 2016–18, the average annual number of adults treated for any skin cancer was 5.8 (95% CI: 5.2, 6.4) and 6.1 (95% CI: 5.6, 6.6) million, respectively, while the average annual number of adults treated for non-skin cancers rose from 10.8 (95% CI: 10.0, 11.5) to 11.9 (95% CI: 11.2, 12.6) million, respectively. The overall estimated annual costs rose from $8.0 (in 2012–2015) to $8.9 billion (in 2016–18) for skin cancer treatment and $70.2 to $79.4 billion respectively for non-skin cancer treatment. Conclusion: The prevalence and economic cost of skin cancer treatment modestly increased in recent years. Given the substantial cost of skin cancer treatment, continued public health attention to implementing evidence-based sun-safety interventions to reduce skin cancer risk may help prevent skin cancer and the associated treatment costs. [ABSTRACT FROM AUTHOR]

The purpose of this article is to review the objectives of the American College of Surgeons Commission on Cancer Operative Standards with a specific focus on Standard 5.5, which pertains to curative intent wide local excision of primary cutaneous melanoma lesions. We review the details and rationale of the standard itself, including its requirement to include specific elements and responses in synoptic format in operative reports. [ABSTRACT FROM AUTHOR]

Over five million cases of skin cancer are diagnosed each year in the United States with melanoma the third most common cancer in young adults. While publications have shown that sunburns increase the risk of developing melanoma throughout the lifetime including in adolescence and adulthood showing the importance of altering sun exposing behaviors throughout the lifetime, use of sun protection in college students remails low. In Fall 2019, an online survey of undergraduate students living on campus at a large southwestern university was conducted to determine the frequency of recent sunburns as well as sun protective behaviors and perceived knowledge of and barriers to sun protection. Associations between knowledge, behaviors, and barriers with self-reported sunburn were evaluated using logistic regression. Over 46% of 458 students reported at least one sunburn in the past three months and 21% reported having multiple sunburns in that period. Furthermore, 53% reported that they intentionally tanned their skin outdoors occasionally or more frequently, while 6.4% reported using an indoor tanning bed occasionally or more. Adjusted for skin sensitivity, recent sunburn history was associated with higher tanning activity scores and with high agreement that tanning was attractive (p < 0.01). This information can inform a more targeted series of intervention programming on the university campus. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to estimate the number of individuals living with metastatic breast, prostate, lung, colorectal, or bladder cancer or metastatic melanoma in the United States using population-based data.Methods: A back-calculation method was used to estimate the number of individuals living with metastatic cancer for each cancer type from US cancer mortality and survival statistics from the Surveillance, Epidemiology, and End Results registries. The percentages of those living with metastatic cancer who advanced to metastatic disease from early stage cancer vs who were diagnosed with metastatic cancer de novo were calculated. One- and 5-year relative survival rates for de novo metastatic cancer were compared by year of diagnosis to assess time trends in survival.Results: It is estimated that, in 2018, 623 405 individuals were living with metastatic breast, prostate, lung, colorectal, or bladder cancer, or metastatic melanoma in the United States. This number is expected to increase to 693 452 in 2025. In 2018, the percentage of metastatic cancer survivors who were initially diagnosed with early stage cancer and advanced to metastatic cancer ranged from 30% for lung cancer to 72% for bladder cancer.Conclusions: This study demonstrates increasing numbers of individuals living with metastatic cancer of the 6 most common cancer types in the United States. This information is critical for informing the allocation of research efforts and healthcare infrastructure needed to address the needs of these individuals. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite significant survival improvements for adolescents and young adults (AYAs) with cancer overall, several subsets of AYAs lag behind. This is especially true for AYAs diagnosed with metastatic disease, where, for many types of cancer, fewer than 20% of patients are alive 5 years later. Which sociodemographic subgroups of AYAs are at highest risk for presenting with metastatic disease is not well understood. In this study using United States Surveillance, Epidemiology, and End Results Program data, we found significantly increased risk of metastatic disease across many cancer sites for non-Hispanic Blacks, males, and low socioeconomic status AYAs. In particular, metastatic melanoma was striking for demonstrating multiple sociodemographic disparities. Results of this study shed light on the relative roles of age, race/ethnicity, sex, and socioeconomic status in metastatic disease presentation. These will inform future, cancer-specific research to elucidate biological, social, and environmental mechanisms underlying these associations with metastatic disease. Having metastatic disease at diagnosis poses the great risk of death among AYAs with cancer from all sociodemographic subgroups. This "landscape" study utilized United States Surveillance, Epidemiology, and End Results Program data from 2000–2016 to identify subgroups of AYAs at highest risk for presenting with metastases across twelve cancer sites having a poor-prognosis (5-year survival <50% with metastases). Adjusted odds ratios for risk of metastatic disease presentation were compared for AYAs in aggregate and by sociodemographic subgroup (race/ethnicity, sex, socioeconomic status [SES]). In general, AYAs who were male, racial/ethnic minorities, or low SES were at consistently greatest risk of metastases. Strikingly, having metastatic melanoma was independently associated with multiple AYA sociodemographic subgroups, including males (aOR 3.11 [95% CI 2.64–3.66]), non-Hispanic Blacks (4.04 [2.32–7.04]), Asian Pacific Islanders (2.99 [1.75–5.12]), Hispanics (2.37 [1.85–3.04]), and low SES (2.30 [1.89–2.80]). Non-Hispanic Blacks were more likely to present with metastatic cancer in all sites, except for bone, rhabdomyosarcoma, and stomach. Low SES AYAs are more likely to present with metastatic melanoma, bone tumors, soft tissue sarcomas, breast, cervical, lung, and stomach carcinomas. Building on these results, future cancer-specific studies should investigate the connection between sociodemographic risk factors and biological drivers of metastases. This line of research has potential to inform targeted public health and screening efforts to facilitate risk reduction and earlier detection of these deadly diseases. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and noncutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined 3 US prospective cohorts, the Health Professionals Follow-up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding nonmelanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 men; 212,449 women) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as referent, for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared with the lowest quintile, risk of any cancer was slightly increased across all other quintiles (highest quintile hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.01, 1.07; P for heterogeneity = 0.41). All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR = 1.17, 95% CI: 1.04, 1.31; P for heterogeneity = 0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and noncutaneous cancers. [ABSTRACT FROM AUTHOR]

Background/purpose: Melanomas account for only approximately 4% of diagnosed skin cancers in the United States but are responsible for the majority of deaths caused by skin cancer. Both genetic factors and ultraviolet (UV) radiation exposure play a role in the development of melanoma. Although melanomas have a strong propensity to metastasize when diagnosed late, melanomas that are diagnosed and treated early pose a low mortality risk. In particular, the identification of patients with increased metastatic risk, who may benefit from early adjuvant therapies, is crucial, especially given the advent of new melanoma treatments. However, the accuracy of classic clinical and histological variables, including the Breslow thickness, presence of ulceration, and lymph node status, might not be sufficient to identify such individuals. Thus, there is a need for the development of additional prognostic melanoma biomarkers that can improve early attempts to stratify melanoma patients and reliably identify high‐risk subgroups with the aim of providing effective personalized therapies. Methods: In our current work, we discuss and assess emerging primary melanoma tumor biomarkers and prognostic circulating biomarkers. Results: Several promising biomarkers show prognostic value (eg, exosomal MIA (ie, melanoma inhibitory activity), serum S100B, AMLo signatures, and mRNA signatures); however, the scarcity of reliable data precludes the use of these biomarkers in current clinical applications. Conclusion: Further research is needed on several promising biomarkers for melanoma. Large‐scale studies are warranted to facilitate the clinical translation of prognostic biomarker applications for melanoma in personalized medicine. [ABSTRACT FROM AUTHOR]

Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients. [ABSTRACT FROM AUTHOR]

Background: Although the recent drop in melanoma mortality has been attributed to the introduction of newer therapies, the impact of ongoing public efforts remains unknown., Objective: Characterize and model melanoma mortality trends before the era of molecular and immune therapies (1969-2014) in the U.S. and Australia., Methods: Differential time series analysis based on population-ascertained melanoma mortality rates from the U.S. and Australia. Mortality rates were modeled and compared to the trajectories of ten other cancers., Results: Melanoma mortality rates have been significantly decelerating since the 1970s in both the U.S. (P < .0001) and Australia (P = .0021). Zero acceleration occurred around 2001 (95% CI: 1996, 2008) for the U.S. and 2004 (95% CI: 1999, 2011) for Australia. Male mortality rates decelerated 3x-4x faster than females in both countries. Melanoma mortality followed a similar quadratic function (R 2  > 0.9) to 10 other cancers, albeit with a later inflection point (1986 vs 2001) and broader focal width., Limitations: Absolute mortality data used without further stratification or considering cancer incidence or covariates., Conclusion: Melanoma deaths have been decelerating for the past 5 decades, reaching an inflection point around 2001, suggesting that mitigating campaigns were already afoot in both the U.S. and Australia before the advent of modern therapies., Competing Interests: Conflicts of interest None declared., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Melanoma is the most commonly fatal type of skin cancer, and it is an important and growing public health problem in the United States and worldwide. Fortunately, incidence rates are decreasing in young people, stabilizing in middle-aged people, and increasing in older individuals. Herein, the authors further describe trends in melanoma incidence and mortality, review the literature on risk factors, and provide an up-to-date assessment of population-wide screening and new technology being utilized in melanoma screening., Competing Interests: Disclosure The authors have nothing to disclosure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Introduction: Previous population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States., Methods: A review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death., Results: Most melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%)., Conclusions: The public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The low expectation of clinical benefit from phase 1 cancer therapeutics trials might negatively affect patient and physician participation, study reimbursement, and slow the progress of oncology research. Advances in cancer drug development, meanwhile, might have favourably improved treatment responses; however, little comprehensive data exist describing the response and toxicity associated with phase 1 trials across solid tumours. The aim of the study is to evaluate the trend of toxicity and response in phase 1 trials for solid tumours over time.Methods: We analysed patient-level data from the Cancer Therapy Evaluation Program of the National Cancer Institute-sponsored investigator-initiated phase 1 trials for solid tumours, from Jan 1, 2000, to May 31, 2019. We assessed risks of treatment-related death (grade 5 toxicity ratings possibly, probably, or definitely attributable to treatment), all on-treatment deaths (deaths during protocol treatment regardless of attribution), grade 3-4 toxicity, and proportion of overall response (complete response and partial response) and complete response rate in the study periods of 2000-05, 2006-12, and 2013-2019, and evaluated their trends over time. We also analysed cancer type-specific and investigational agent-specific response, and analysed the trend of response in each cancer type over time. Univariate associations of overall response rates with patients' baseline characteristics (age, sex, performance status, BMI, albumin concentration, and haemoglobin concentration), enrolment period, investigational agents, and trial design were assessed using risk ratio based on the modified Poisson regression model.Findings: We analysed 465 protocols that enrolled 13 847 patients using 261 agents. 144 (31%) trials used a monotherapy and 321 (69%) used combination therapies. The overall treatment-related death rate was 0·7% (95% CI 0·5-0·8) across all periods. Risks of treatment-related deaths did not change over time (p=0·52). All on-treatment death risk during the study period was 8·0% (95% CI 7·6-8·5). The most common grade 3-4 adverse events were haematological; grade 3-4 neutropenia occurred in 2336 (16·9%) of 13 847 patients, lymphopenia in 1230 (8·9%), anaemia in 894 (6·5%), and thrombocytopenia in 979 (7·1%). The overall response rate for all trials during the study period was 12·2% (95% CI 11·5-12·8; 1133 of 9325 patients) and complete response rate was 2·7% (2·4-3·0; 249 of 9325). Overall response increased from 9·6% (95% CI 8·7-10·6) in 2000-05 to 18·0% (15·7-20·5) in 2013-19, and complete response rates from 2·5% (2·0-3·0) to 4·3% (3·2-5·7). Overall response rates for combination therapy were substantially higher than for monotherapy (15·8% [15·0-16·8] vs 3·5% [2·8-4·2]). The overall response by class of agents differed across diseases. Anti-angiogenesis agents were associated with higher overall response rate for bladder, colon, kidney and ovarian cancer. DNA repair inhibitors were associated with higher overall response rate in ovarian and pancreatic cancer. The rates of overall response over time differed markedly by disease; there were notable improvements in bladder, breast, and kidney cancer and melanoma, but no change in the low response of pancreatic and colon cancer.Interpretation: During the past 20 years, the response rate in phase 1 trials nearly doubled without an increase in the treatment-related death rate. However, there is significant heterogeneity in overall response by various factors such as cancer type, investigational agent, and trial design. Therefore, informed decision making is crucial for patients before participating in phase 1 trials. This study provides updated encouraging outcomes of modern phase 1 trials in solid tumours.Funding: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4–12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies. • The efficacy of immunotherapy for melanoma in-transit metastases is unknown. • An international multicenter retrospective cohort study. • Systemic immunotherapy is an effective treatment for melanoma in-transit metastases. [ABSTRACT FROM AUTHOR]

Objective: Racial and ethnic health disparities affect the diagnosis and management of melanoma and nonmelanoma skin cancers, leading to deleterious outcomes. Non-Hispanic White patients make up the majority of skin cancers cases, yet racial and ethnic minorities have poorer prognoses and outcomes. The skin cancer literature is fragmented with regards to potential contributors to these healthcare disparities. In this article, we provide a comprehensive review of the skin cancer literature to briefly quantify racial and ethnic inequities, highlight contributing factors, and propose practical changes that can be made.Methods: A PubMed search was completed to identify articles related to racial and ethnic health care disparities in the context of melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and dermatofibrosarcoma protuberans.Results: Relative to non-Hispanic White patients, patients of racial and ethnic minorities have differing clinical presentations of skin cancers and genetic risk factors. Insurance, access to specialty care, cultural beliefs, and available educational resources further contribute to racial and ethnic disparities.Limitations: We are limited to the level of detail provided in the existing literature, and at some times are unable to distinguish race of Hispanic populations. We also acknowledge that there are different nationalities grouped under these broad labels as well as multi-racial populations that may not be accounted for.Conclusion: Awareness of and familiarization with innate factors and potentially more modifiable contributors can help inform efforts to close the observed gap in racial and ethnic inequities. [ABSTRACT FROM AUTHOR]

The incidence of non‐melanoma skin cancer is on the rise and melanoma is among the most common cancers in the United States. Establishing an early diagnosis is essential for improving the prognosis of patients with skin cancer. High‐resolution non‐invasive imaging techniques may represent key tools for helping to identify and monitor early signs of skin cancer in seemingly healthy skin. Cumulative lifetime sun exposure leads to photoaging and photocarcinogenenis and the reaction of the skin to this solar‐induced damage is balanced between the DNA repair and photoprotection defence mechanisms of melanocytes and keratinocytes. In the first part of this article we provide an overview of these defence mechanisms and of the photoaging process, and discuss how non‐invasive imaging can be used to evaluate these changes. We then propose a model in which skin aging manifestations can be classified according to subject‐specific sun‐damage reaction profiles observed by reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). These photoaging profiles include an atrophic phenotype characterized by actinic keratosis, and a hypertrophic phenotype characterized by hyperplastic pigmented skin. According to our model, these phenotypes may be predictive of predispositions to different types of skin cancer: squamous cell carcinoma for the atrophic phenotype and lentigo maligna and freckles for the hypertrophic phenotype. In addition to RCM and OCT, dermoscopy is another non‐invasive technique that has improved the diagnosis of skin cancer. In the second part of this article, we describe how the YouDermoscopy™ application can improve skills and thus enhance the dermoscopic recognition of sun‐induced skin tumours, and then show how this training tool enables its users to collaborate with dermatologists worldwide to obtain second opinions for the diagnosis of ambiguous lesions. Altogether, RCM, OCT and dermoscopy are valuable tools that can contribute significantly to improving the early diagnosis of precancerous and cancerous lesions. [ABSTRACT FROM AUTHOR]

Objectives: Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. Methods: We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. Results: White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 μg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. Conclusions: We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated. [ABSTRACT FROM AUTHOR]

Background: The tumor, nodes and metastasis (TNM) classification and stage grouping have been updated in the 8th edition of the American Joint Committee on Cancer (AJCC) melanoma staging manual. However, restaging all the previous cases are not recommended.Aims: The aims of the study were to investigate the necessity of restaging Korean melanoma patients staged by the previous edition of the AJCC manual.Methods: Differences in the staging criteria of the 7th and 8th editions of the AJCC manual were identified. The staging of 276 primary melanomas from January 2011 to December 2018 was classified by both 7th and 8th editions of the manual and their differences were compared.Results: Staging by 7th and 8th edition of the AJCC manual differed in 64 cases (23.2%). The pathological prognostic staging changed in 35 (12.7%), and 29 (10.5%) had changes in only TNM classification but not the pathological staging. None of the patients needed additional sentinel lymph node biopsy or systemic treatment as a result of restaging. Additional counseling was needed for the patients, because melanoma-specific survival was increased in the 8th edition.Limitations: This is a retrospective study with relatively small number of patients at a single tertiary center in Korea.Conclusion: Assessment of the need for additional sentinel lymph node biopsy or systemic treatment is recommended because of the latest changes in the AJCC melanoma staging manual. Although the restaging of previously staged melanomas is not significantly needed in our patients, still the differences in TNM classification and/or pathological prognostic staging suggest the need to separately recognize the patients previously staged by 7th edition and recently staged by 8th edition. Careful counseling about melanoma-specific survival is needed for Asian patients. [ABSTRACT FROM AUTHOR]

Background: New research has attributed increased significance to the causal link between ultraviolet A (UVA) radiation and immunosuppression and carcinogenesis. In the United States, sunscreens are labeled with only their sun protection factor (SPF) and an imprecise term "broad‐spectrum protection." Sunscreen marketing and efficacy evaluations continue to be based primarily on skin redness (sunburn) or erythema. We sought to evaluate the ultraviolet (UV) protection offered by common sunscreen products on the US market using laboratory‐measured UV‐absorption testing and comparing with computer‐modeled protection and the labeled SPF values. This approach enables an investigation of the relationship between the labeled SPF and measured UVA protection, a factor that is ignored in current regulations. Methods: Fifty‐one sunscreen products for sale in the United States with SPF values from 15 to 110 and labeled as providing broad‐spectrum protection were tested using a commercial laboratory. All products were evaluated using the ISO 24443:2012 method for sunscreen effectiveness. The final absorbance spectra were used for analysis of in vitro UV protection. Results: In vitro SPF values from laboratory‐measured UV absorption and computer modeling were on average just 59 and 42 percent of the labeled SPF. The majority of products provided significantly lower UVA protection with the average unweighted UVA protection factor just 24 percent of the labeled SPF. Conclusion: Regulations and marketplace forces promote sunscreens that reduce sunburn instead of products that provide better, more broad‐spectrum UV protection. The production and use of products with broad spectrum UV protection should be incentivized, removing the emphasis on sunburn protection and ending testing on people. [ABSTRACT FROM AUTHOR]