Melanoma Survival Research Articles

Expression Patterns of DLL3 Across Neuroendocrine and Non-Neuroendocrine Neoplasms Reveal Broad Opportunities for Therapeutic Targeting.

Neuroendocrine neoplasms (NENs) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development and expansion of DLL3-targeted therapies, we sought to characterize the expression of DLL3 and identify its clinical and molecular correlates across diverse neuroendocrine and non-neuroendocrine cancers. Here, we interrogated paired DNA and RNA-sequencing from 1,589 NENs across 29 sites, as well as 203,252 tumors across 47 cancer types. We found that high transcriptomic levels of DLL3 correlated with more aggressive histologic and mutational patterns in NENs, with adverse survival outcomes being reflected in NENs originating from the lung, pancreas, stomach, and small bowel. The heterogeneity in DLL3 expression across NENs was largely explained by site of origin, with lung, prostate, and bladder NENs exhibiting relatively high levels of DLL3 whereas gastroenteropancreatic (GEP) NENs displayed relatively low expression levels. Although the therapeutic targeting of DLL3 may be less applicable for GEP-NENs, we did find an upregulation of alternative targets such as SEZ6, CELSR3, and SSTR2 in these settings. Lastly, expanding our investigation into non-neuroendocrine cancers, we detected an enrichment of DLL3 in both low-grade and high-grade gliomas, Merkel cell carcinomas, medulloblastomas, and melanomas, with such enrichment being associated with prolonged overall survival in gliomas, but worse overall survival in melanomas. Altogether, we demonstrate that DLL3 represents an attractive target for subsets of neuroendocrine and non-neuroendocrine cancers and uncover opportunities for future therapeutic strategies.

Sex Differences in Melanoma Survival-a GEM study.

Sex differences in melanoma are prominent, with females having a significant survival advantage. However, it is unclear why we see this survival advantage. Here we investigate the relationship between sex, clinicopathologic variables, and melanoma specific survival in 1,753 single primary melanomas from patients in the GEM study. Using Cox proportional hazard models and formal mediation analysis, the effect of sex on survival is explained largely by differences in the clinicopathologic features of tumors at diagnosis. Specifically, we find evidence that 86.5% of the effect of sex on melanoma survival is mediated by differences in age at diagnosis, Breslow thickness, ulceration, mitoses and site (HR 1.85, P < .001). This analysis indicates that the female survival advantage in melanoma is not due primarily to a direct effect of sex (HR 1.19, P = .42) but is largely a result of an indirect effect of sex mediated by clinicopathologic features.

The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis.

PRAME is a cancer testis antigen whose expression is limited in normal tissues but is increased in cancers. Although there are studies revealing its oncogenic and immunogenic role, the relationship between PRAME expression and immunity in melanomas is not very clear. We aimed to reveal the relationship between PRAME expression and clinicopathologic parameters, immunologic markers, survival in melanomas. PRAME alteration data in TCGA SKCM data set was obtained from cBioPortal. Analyzes regarding clinicopathologic parameters were performed through cBioPortal and UALCAN, survival-related analyzes were performed through cBioPortal, GEPIA2. The correlation analyzes between PRAME expression and immune cell infiltration, immunity-related genes were performed in TIMER2.0, TISIDB, GEPIA2. PRAME protein-protein interaction network was constructed in STRING. The correlated genes with PRAME were listed in LinkedOmics, gene set enrichment and pathway analyses were performed through LinkInterpreter. In cases with low PRAME expression, there was a higher frequency of metastasis and p53 mutation, a more advanced tumor stage and a lower nodal stage. Strong relationship between PRAME expression and immune cell infiltration. A negative correlation was detected between expression of PRAME and many immunomodulatory genes (P<0.05). Positively correlated genes with PRAME expression were involved in metabolic pathways; negatively correlated genes were involved in pathways related to cell differentiation, immunologic processes. No significant relationship was found between PRAME expression and survival (P>0.05). Our findings reveal a strong interaction between PRAME expression and tumorigenicity, the immune system and shed light on further clinical studies including PRAME-targeted studies.

Melanoma detection, treatment, survival, and mortality through year 2 of the pandemic

The COVID-19 pandemic affected the timely diagnosis and treatment of many cancers, including melanoma, the fifth most common cancer in the U.S. This study aimed to quantify the disruption and recovery of melanoma detection, treatment, survival, and mortality during the pandemic by analyzing data from the Surveillance, Epidemiology, and End Results (SEER) program from 2000 to 2021. Our epidemiological analysis found that melanoma incidence initially dropped by 14.8% (95% CI: − 17.2 to − 12.4) in 2020 compared to pre-pandemic projections. Although incidence rates substantially recovered by 2021, an estimated 10,274 patients (95% CI: − 12,824 to − 7,724) remained undiagnosed due to pandemic-related disruptions. Time-to-treatment and 1-year survival were mostly consistent with pre-pandemic trends, while melanoma-specific mortality modestly declined by 4.5% (95% CI: − 14.6 to 5.6) in 2021, though this was statistically non-significant. These findings suggest that healthcare systems adapted to the challenges posed by the pandemic, maintaining essential cancer services. However, the significant drop in melanoma diagnoses likely contributed to the observed reduction in mortality. Thus, re-establishing care for patients missed during the pandemic will be crucial to preventing a future increase in advanced-stage melanoma and related deaths.

Stat Bite: Improvements in 5-year Relative Survival for Regional and Distant Stage Melanoma of the Skin

Stat Bite: Improvements in 5-year Relative Survival for Regional and Distant Stage Melanoma of the Skin

Sex differences in survival from melanoma of the skin: The role of age, anatomic location and stage at diagnosis: A CONCORD-3 study in 59 countries.

CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Studies showed a survival advantage in women, but the reasons are not completely understood. We aim to estimate trends in age-standardised 5-year net survival by sex and to examine the role of age, anatomic location and stage on the survival advantage for women worldwide. Patients were grouped into five anatomic locations (head and neck, trunk, limbs, genital organs and not otherwise specified locations), into five age groups (15-29, 30-44, 45-59, 60-74 and 75-99 years) and into binary stage (non-metastatic vs. metastatic). We estimated net survival with the non-parametric Pohar Perme estimator, correcting for background mortality by single-year of age, sex, race/ethnicity where possible and calendar year in each country. All-ages estimates were standardised with the International Cancer Survival Standard weights. Men were generally older and with higher proportion of metastatic melanomas than women. Overall, the trunk was the most common location in men (range 31 %-58 %) and the lower limbs and hips in women (26 %-40 %). Age-standardised 5-year net survival was lower in men (43 %-92 %) than in women (54 %-95 %) in all countries during 2010-2014 and it was lower at older ages for both sexes. A survival advantage for women was observed for all anatomic sites and for localised disease. Women had a more favourable distribution of main prognostic factors, and showed highest survival for any prognostic factor. Public health efforts should focus on raising awareness of early signs of melanoma, especially among elderly in South-East Europe and to increase awareness in East-Asia, where survival was poorest.

A Comparative Study of Merkel Cell Carcinoma and Melanoma Incidence and Survival in the United States, 2000-2021.

Merkel cell carcinoma (MCC) and melanoma are important contributors to skin cancer mortality in the United States. We evaluated their epidemiology using the United States cancer registry data. In 2000-2021, 19,444 MCCs and 646,619 melanomas of the skin were diagnosed. Ninety percent of MCCs and 95% of melanomas were in non-Hispanic White individuals. More than 70% of MCCs versus 37% of melanomas occurred in people aged ≥70 years. Excess MCCs and melanomas were observed on the head and neck (observed:expected: MCC, 5.15; melanoma, 2.47). Among non-Hispanic White individuals, ambient UVR exposure was associated with melanoma arising on the head and neck (incidence rate ratios of 1.15-1.20 for MCC and 1.24-1.49 for melanoma, comparing quintiles 3-5 with quintile 1). Cancer-specific mortality was higher among patients with MCC than among those with melanoma (hazard ratio= 2.33, 95% confidence interval= 2.26-2.42) but improved in both groups after 2011 when BRAF and checkpoint inhibitors were introduced. In conclusion, melanoma exhibited stronger associations with race and ambient UVR exposure, while MCC was more likely to arise on the head and neck (perhaps reflecting the distribution of precursor cells). To ensure prompt treatment, clinicians should be on alert when diagnosing these cancers.

Neoadjuvant immunotherapy in melanoma: pathological response as a surrogate endpoint?

This review evaluates by analyzing recent studies whether pathological complete response (pCR) can be used as a reliable surrogate marker for overall survival (OS) in melanoma treated with neoadjuvant immunotherapy. Trials like Neo-Combi, Neo-Trio and COMBI-Neo show that pCR is crucial for long-term success in targeted therapy for melanoma, while studies like OpACIN-neo and SWOG S1801 demonstrate that immunotherapy can provide durable benefits even with partial responses. Findings from NADINA and the INMC analysis highlight that immunotherapy achieves higher pathologic response rates and improved survival outcomes, offering broader benefits compared to the pCR-dependent outcomes of targeted therapy. pCR serves as a critical prognostic biomarker across cancer types, with strong validation in breast cancer where it predicts long-term survival, particularly in aggressive subtypes like triple-negative and HER2-positive breast cancer. In melanoma, pCR is gaining prominence as a surrogate marker in neoadjuvant therapies, with its predictive value varying between targeted treatments - where achieving pCR is essential - and immunotherapies, which provide durable survival benefits even with partial responses. Despite its potential, the role of pCR as a universally reliable surrogate endpoint in melanoma requires further validation through cancer-specific studies to ensure accurate treatment guidance and personalized care.

Novel FANCI and RAD54B Variants and the Observed Clinical Outcomes in a Hungarian Melanoma Cohort.

Accumulating evidence suggests that inherited melanoma is not rare and approx. one in seven individuals with melanoma has clinically relevant hereditable cancer-predisposing and/or -susceptibility variant(s). Concerning its germline genetic background, genetic screening aims to identify either variants of predisposing genes with high penetrance or variants of susceptibility genes with medium or low penetrance. However, less attention is paid to genetic testing of germline variants of genes influencing patients' survival outcomes or enhancing the design of new therapies. We aimed to investigate whether the germline genetic background of a Hungarian melanoma cohort (n = 17) contains any pathogenic or likely pathogenic variants of the BRCA2, POLE, WRN, FANCI, PALB2, and RAD54B genes and if the presence of these variants correlate with the clinical findings of the patients, including the advanced stage of melanoma, poor prognosis, and poor survival. We identified three novel variants in the FANCI gene and one novel variant in the RAD54B gene. We detected rapid disease progression, unfavorable outcome, and therapeutic resistance in the patient carrying the likely pathogenic FANCI variant. Our study highlights the importance of screening germline variants of genes influencing melanoma progression, therapy resistance, and survival of patients.

Uveal Melanoma: 5-Year Update on Incidence, Treatment, and Survival (SEER 1975–2020)

Introduction: Since 2003, using the Surveillance, Epidemiology, and End Results (SEER) database, epidemiological aspects of uveal melanoma have been reported. The aim of this study was to update trends in incidence, treatment, and survival of uveal melanoma in the USA from 1975 to 2020. Methods: Patients were identified using International Classification of Disease for Oncology codes: C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]. Trends in age-adjusted incidence, treatment (surgery or radiation), and 5-year relative survival were calculated. Results: A total of 5,563 cases of uveal melanoma were identified. The majority (97%) were reported by hospital inpatient/outpatient clinics. Microscopic (histopathologic or cytologic) confirmation was available in 61%. The mean age-adjusted incidence was 5.6 per million (95% CI: 5.5–5.7). As previously noted, a small but statistically significant (p < 0.05) annual percentage change of 0.5% was detected in whites. The previously reported declining trend in the number of patients treated with surgery alone (93% from 1975 to 1977 vs. 21% from 2017 to 2020) ensued, with ongoing corresponding increasing rates of radiation as the primary treatment (1% from 1975 to 1977 vs. 58% from 2017 to 2020). No change in the 5-year relative survival (82.8%) was observed (reported from 1975 to 2016). Conclusions: Previously reported overall age-adjusted incidence of uveal melanoma is stable throughout the years, with a minor increase in incidence in whites. Treatment trend toward radiation has not led to improvement in survival.

P106 Genome-Wide Association Study of a rare papulosquamous disease: pityriasis rubra pilaris

Abstract Pityriasis rubra pilaris (PRP) is a rare chronic skin disorder that causes persistent inflammation, thickening and shedding of the skin. In terms of classification, it is a papulosquamous disease and its clinical features that have the closest overlap with psoriasis. Genetic studies have thus far identified variants in the CARD14 gene that contribute to the susceptibility of PRP, but a genome-wide association study (GWAS) has not yet been conducted. Therefore, it was our aim to perform a GWAS using the genotype data of nearly 200 000 individuals available from the Estonian Biobank database (EstBB). The patients included 100 EstBB participants who had a registered ICD-10 diagnosis code for PRP–L44.0. The control group consisted of 199 647 individuals who did not have the L44.0 diagnosis. An additive GWAS was performed using the SAIGE program adjusting for age, sex, and the first 10 genetic principal components. Since the group of patients was smaller than typically used in GWAS, we lowered the threshold for statistical significance to P &amp;lt; 5 × 10−7. The FUMA platform was used for functional annotation of association signals. Significant associations appeared in genomic regions of chromosome 4 [single nucleotide polymorphism (SNP) rs115367424, P = 2.08 × 10−7], chromosome 6 (lead SNP rs142103230, P = 5.71 × 10−8) and chromosome 14 (lead SNP rs8012648, P = 2.44 × 10−7). The nearest gene to rs115367424 is CCSER1, which has been associated with poor melanoma survival. The candidate SNPs of chromosome 6 are situated within an intron of PRKN gene that functions as a modulator of innate immunity to infectious agents and its genetic variants have been associated with susceptibility to leprosy. Chromosome 14 candidate SNPs are intronic variants of FBLN5 gene that can promote dermal wound healing and attenuate burn injury-induced inflammatory responses. The results presented here require confirmation in future studies, and the identification of possible functional variants in the three discussed genomic regions calls for further investigation. Genetic research on PRP is challenging due to its very rare occurrence, but considering the severity of the disease, this scientific attention is still very much needed.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers. Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing clinical and transcriptomic data from 1892 patients diagnosed with melanoma, bladder, ovarian, or pancreatic carcinomas. Real-world data were collected under the Total Cancer Care Protocol and the Avatar® project (NCT03977402) across 18 cancer centers. Furthermore, we compared the survival outcomes following immune checkpoint inhibitors (ICIs) based on immune cell gene expression. Results: In melanoma and bladder cancer, the estimated infiltration of APA T-cells differed significantly (p = 4.67 × 10-12 and p = 5.80 × 10-12, respectively) compared to ovarian and pancreatic cancers. Ovarian cancer had lower TRM T-cell infiltration than melanoma, bladder, and pancreatic (p = 2.23 × 10-8, 3.86 × 10-28, and 7.85 × 10-9, respectively). Similar trends were noted with stem-like, early, and late dysfunctional T-cells. Melanoma and ovarian expressed BTN3A isoforms more than other malignancies. Higher densities of stem-like TILs; TRM, early and late dysfunctional T-cells; APA T-cells; and BTN3A isoforms were associated with increased survival in melanoma (p = 0.0075, 0.00059, 0.013, 0.005, 0.0016, and 0.041, respectively). The TRM gene signature was a moderate predictor of survival in the melanoma cohort (AUROC = 0.65), with similar findings in testing independent public datasets of ICI-treated patients with melanoma (AUROC 0.61-0.64). Conclusions: Key cellular elements related to immune activation are more heavily infiltrated within ICI-responsive versus non-responsive malignancies, supporting a central role in anti-tumor immunity. In melanoma patients treated with ICIs, higher densities of stem-like TILs, TRM T-cells, early dysfunctional T-cells, late dysfunctional T-cells, APA T-cells, and BTN3A isoforms were associated with improved survival.

Patient and Tumor Factors on Overall Survival in Spindle Cell Melanoma

Patient and Tumor Factors on Overall Survival in Spindle Cell Melanoma

Trends in incidence, mortality, and survival of cutaneous malignant melanoma over three decades: a population-based study in Southern Spain.

Cutaneous malignant melanoma (CMM) represents a global public health problem. Epidemiological studies about CMM trends tend to focus on single indicators or lack information about tumor characteristics that can help gain a more thorough understanding of CMM epidemiology. To fill this gap, we studied CMM trends in incidence, mortality, and survival over three decades and considering sex, age, and tumor characteristics. Data were obtained for all new cases of CMM diagnosed 1985-2017 from the population-based cancer registry in Granada (Southern Spain) and for deaths due to CMM by the Ministry of Health of the Spanish government. Incidence, mortality, and survival estimates were obtained according to sex, age group, anatomical site, histological type, Breslow index, and Clark level. Observed and net survival were calculated for 1, 3, and 5 years using the Kaplan-Meier and Pohar-Perme methods, respectively. Log-linear jointpoint regression was used to assess temporal trends in age-standardized rates of incidence and mortality. Between 1985-2017, 2,446 patients aged 15 years and older were newly diagnosed with CMM. There was a significant increase in incidence, both in men and women (APC 4.4% and 3.7% respectively), mainly in superficial spreading and nodular melanomas, and more pronounced among those with <1mm Breslow index. Mortality rates increased, mainly driven by increases among men and individuals ≥65 years old. Nodular melanoma had the worst prognosis, with a 5-year observed survival of 67.1% compared to survival greater than 90% for the other subtypes. 5-year net survival improved from 78.3% in 1985-1997 to 88.6% in 2008-2017, with a clear trend by Breslow index. The incidence of melanoma in early stages in Southern Spain has increased over the past decades. This has been accompanied by noticeable improvements in mortality and survival, especially among younger age groups, suggesting the potential effectiveness of prevention strategies, and new treatment regimens.

Trends in Cutaneous Melanoma in Nova Scotia With a Focus on 2007 to 2019.

Melanoma represents a significant public health challenge in Canada, contributing to the deaths of over 1000 individuals each year. Prince Edward Island and Nova Scotia were previously noted to have the highest incidence rates of melanoma in Canada. Data from patients diagnosed with or dying from melanoma was extracted from the Nova Scotia Cancer Registry. TNM stage was available for cases diagnosed 2007 to 2017. Incidence (1992-2019) and mortality (1992-2021) rates were examined using Join Point Trend Analysis Software. Between 2007 and 2019, 2450 cases of in situ and 4063 cases of invasive melanoma were documented, of which 52.8% were male. The largest number of cases was from the 60- to 79-year age group. The most common site in females was upper limbs (in situ) and lower limbs (invasive), and for males, face, and neck (in situ), and trunk (invasive). The majority of invasive cases (71.5%) were diagnosed at stage I. Invasive melanoma incidence has been increasing by 2.7% per year since 1992, while in situ disease has increased at a greater rate (4.9% per year). The current estimate of 92% for 5 years of net survival has not changed appreciably over the same period. Survival for late-stage melanoma has shown a modest improvement for patients diagnosed over the period. With increasing rates of melanoma in Nova Scotia, there is a need for informed education, directed at the public and physicians, around pigmented skin lesions. This would allow the patient to detect atypical melanocytic lesions at an early stage. Sun safety practices in Nova Scotia should continue to be encouraged.

Abstract B044: Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival

Abstract The levels of circulating tumour DNA (ctDNA) in cancer patients are associated with response and survival outcomes. Analysis of ctDNA generally requires knowledge of tumour mutations or the application of expensive next generation targeted sequencing. Here we utilize a cutting-edge approach, combining cell-free DNA molecules (cfDNA) fragmentomics and machine learning, to infer the presence of ctDNA to predict response and survival to immune checkpoint inhibitors in stage III unresectable and IV melanoma patients. Genome libraries were constructed from cfDNA derived from 48 (discovery cohort) and 96 (validation cohort) stage III unresectable and IV melanoma patients prior to the commencement of immune-checkpoint inhibitors. The discovery cohort included any-line therapy, patients had a median age of 66, 69% were male, 33% were BRAF V600 mutant, and 88% had an ECOG of 0-1. The validation cohort included first-line therapy, patients had a median age of 69, 59% were male, 22% were BRAF V600 mutant, and 89% had an ECOG of 0-1. Genome libraries were subjected to shallow whole genome sequencing (8x) and the following metrics were calculated: tumour content prediction, aneuploidy levels, various proportions of fragments ranging from 20 bp to 320 bp, the proportion of mitochondrial DNA, and the amplitude of 10 bp size oscillations between 75-150 bp, and the Shannon diversity of trinucleotide motifs at each end of the read. Non-penalized logistic modelling was used to predict clinical benefit, and the resulting logistic model was transformed into a “white-box” model. The white-box model was applied to the cohorts and used to test progression-free and overall survival. The removal of reads with inserts &amp;lt;90 and &amp;gt;150 bp greatly improved chromosome aneuploidy detection from 19% to 31%. Logistic modelling of the fragmentomic features of cfDNA yielded an AUROC of 0.83 for prediction of clinical benefit in the discovery cohort. A cutoff was set for the fragmentomic model score and used to stratify groups for survival analysis. Patients with a low score showed significantly worse progression- free (mPFS 931 vs 286 days, HR 3.4, 95% CI 1.55-7.46, p&amp;lt;0.002) and overall (mOS NR vs 363 days, HR 8.1, 95% CI 2.7-24.3, p&amp;lt;0.001) survival. These results were replicated in the validation cohort with an AUROC of 0.78 for prediction of clinical benefit and significant associations with progression-free (mPFS 1986 vs 926 days, HR 2.33 95% CI 1.27-3.92, p=0.005) and overall (mOS NR vs 1238 days, HR 4.51 95% CI 1.7-11.96, p=0.002) survival. Fragmentomic features of plasma cfDNA enable the prediction of clinical benefit, progression-free, and overall survival in stage IV melanoma patients treated with immune-checkpoint inhibitors. Citation Format: Aaron B Beasley, Leslie Calapre, Ashleigh Stewart, Anna L Reid, Russell Diefenbach, Wei Yen Chan, Rebecca Auzins, Luisa Pinnel, Sanjeev Adhikari, Muhammad A Khattak, Peter Lau, Tarek M Meniawy, Jenny H Lee, Lydia Warburton, Michael Millward, Alexander M Menzies, Richard A Scolyer, Georgina V Long, Helen Rizos, Elin S Gray. Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B044.

Machine Learning-enhanced Signature of Metastasis-related T Cell Marker Genes for Predicting Overall Survival in Malignant Melanoma.

In this study, we aimed to investigate disparities in the tumor immune microenvironment (TME) between primary and metastatic malignant melanoma (MM) using single-cell RNA sequencing (scRNA-seq) and to identify metastasis-related T cell marker genes (MRTMGs) for predicting patient survival using machine learning techniques. We identified 6 distinct T cell clusters in 10×scRNA-seq data utilizing the Uniform Manifold Approximation and Projection (UMAP) algorithm. Four machine learning algorithms highlighted SRGN, PMEL, GPR143, EIF4A2, and DSP as pivotal MRTMGs, forming the foundation of the MRTMGs signature. A high MRTMGs signature was found to be correlated with poorer overall survival (OS) and suppression of antitumor immunity in MM patients. We developed a nomogram that combines the MRTMGs signature with the T stage and N stage, which accurately predicts 1-year, 3-year, and 5-year OS probabilities. Furthermore, in an immunotherapy cohort, a high MRTMG signature was associated with an unfavorable response to anti-programmed death 1 (PD-1) therapy. In conclusion, primary and metastatic MM display distinct TME landscapes with different T cell subsets playing crucial roles in metastasis. The MRTMGs signature, established through machine learning, holds potential as a valuable biomarker for predicting the survival of MM patients and their response to anti-PD-1 therapy.

Sinonasal Mucosal Melanoma Survival Outcomes, Recurrence Patterns, and Prognostic Factors: A Systematic Literature Review and Meta-analysis of Publications after 2000

Abstract Background Sinonasal mucosal melanoma (SNMM) comprises &lt;1% of all head and neck cancers but has one of the highest 5-year mortalities. Methods A systematic review and analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) guidelines was conducted on SNMM survival, recurrence, and prognostic factors. Results A total of 2,379 abstracts were reviewed resulting in 90 studies describing 3347 SNMM patients. Patients were 49.65% male and 66.5 years old. Surgery plus radiation therapy, followed by surgery only, then radiation only were the most common treatments. Chemotherapy and immunotherapy were used in 418 patients and 101 respectively. The 2-, 3-, and 5-year overall survivals are 55.97, 40.09, and 30.35%, respectively. The 5-year disease-free survival and disease-specific survival are 25.56 and 38.04%. The 5-year local, regional, and distant recurrence-free survivals are 42.35, 81.64, and 44.65%. Mean survival after diagnosis was 26.99 months. Local (n = 650), regional (n = 226), and distant (n = 723) failure presented after 19.36, 6.35, and 12.42 months. Sites of metastasis were lung, liver, bone, brain, skin, kidney, and adrenal glands. Distant metastases, disease in the paranasal sinuses, and higher stage were noted to have worse survival outcomes. Positive margins did not significantly impact overall survival in 11/12 studies. Conclusion Overall survival over 20 years has remained poor with 70% of patients deceased in 5 years. About half of patients will develop distant failure and will thereafter rapidly decline. These data indicate need for advances in treatment of SNMM and new efforts with targeted immunotherapy offer a promising avenue toward improving survival outcomes.

Ecto-NOX Disulfide-Thiol Exchanger 2 (ENOX2/tNOX) Is a Potential Prognostic Marker in Primary Malignant Melanoma and May Serve as a Therapeutic Target.

With an increasing incidence of malignant melanoma, new prognostic biomarkers for clinical decision making have become more important. In this study, we evaluated the role of ecto-NOX disulfide-thiol exchanger 2 (ENOX2/tNOX), a cancer- and growth-associated protein, in the prognosis and therapy of primary malignant melanoma. We conducted a tissue microarray analysis of immunohistochemical ENOX2 protein expression and The Cancer Genome Atlas (TCGA) ENOX2 RNA expression analysis, as well as viability assays and Western blots of melanoma cell lines treated with the ENOX2 inhibitor phenoxodiol (PXD) and BRAF inhibitor (BRAFi) vemurafenib. We discovered that high ENOX2 expression is associated with decreased overall (OS), disease-specific (DSS) and metastasis-free survival (MFS) in primary melanoma (PM) and a reduction in electronic tumor-infiltrating lymphocytes (eTILs). A gradual rise in ENOX2 expression was found with an increase in malignant potential from benign nevi (BNs) via PMs to melanoma metastases (MMs), as well as with an increasing tumor thickness and stage. These results highlight the important role of ENOX2 in cancer growth, progression and metastasis. The ENOX2 expression was not limited to malignant cell lines but could also be found in keratinocytes, fibroblasts and melanocytes. The viability of melanoma cell lines could be inhibited by PXD. A reduced induction of phospho-AKT under PXD could prevent the development of acquired BRAFi resistance. In conclusion, ENOX2 may serve as a potential prognostic marker and therapeutic target in malignant melanoma.

Mohs Micrographic Surgery for the Treatment of Lentigo Maligna and Lentigo Maligna Melanoma: An Outcomes Study.

Lentigo maligna (LM), a type of melanoma in situ (MIS), usually develops on sun-damaged skin in the elderly. If left untreated, it may advance to the point of dermal invasion, developing into lentigo maligna melanoma (LMM). While surgeons have achieved robust clinical outcomes for LM treated with Mohs micrographic surgery (MMS), performing this treatment for LMM remains controversial and is not standard amongst all Mohs surgeons. We examined survival outcomes in LM/LMM cases treated with MMS and wide local excision (WLE). Data from the National Cancer Institute Surveillance, Epidemiology, and End Results (NCI SEER) program, collected from 2000-2019, was retrospectively analyzed. Patients with microscopically confirmed diagnosis of LM/LMM who received surgical treatment with MMS or WLE were included. The effect of different surgery types on melanoma survival was evaluated. A total of 22,852 LM/LMM cases performed during the years 2000-2019 were considered for analysis. There were no significant differences in disease-specific survival comparing WLE to MMS. Our research hints at the utility of MMS for LM/LMM. We encourage practitioners to consider MMS for the management LM/LMM when appropriate. J Drugs Dermatol. 2024;23(12):1094-1099.&nbsp; doi:10.36849/JDD.7898.