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Histological subtypes of cutaneous melanoma (NCDB 2004-2015): mortality, lymph node status, and presence of metastasis at diagnosis.
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Simple Summary
Melanoma is clinicopathologically a heterogeneous disease with rising incidence. Metastatic disease is associated with poor outcomes, and immunotherapy was first approved in 2011 for its treatment. In our analysis of a large national database, we describe the epidemiology, clinical presentation, and survival outcomes of cutaneous, oc...
Contexts in source publication
Context 1
... remaining groups were melanoma, NOS (50.31%), and other (4.36%). The majority cases (67.38%) of cutaneous melanoma were Stage 1 at diagnosis ( Table S2a). Table 2 shows the mortality and extent of disease based on the histological subtypes of cutaneous melanoma, while Table 3 analyzes the differences in key characteristics of cutaneous melanoma based on race. ...Context 2
... majority cases (67.38%) of cutaneous melanoma were Stage 1 at diagnosis ( Table S2a). Table 2 shows the mortality and extent of disease based on the histological subtypes of cutaneous melanoma, while Table 3 analyzes the differences in key characteristics of cutaneous melanoma based on race. Amongst cases of ocular melanoma, 90.28% (n = 15,992) originated in the uvea, while 4.95% (n = 877) originated in the conjunctiva. ...Context 3
... <0.001) in contrast to a community cancer program. Table S2b analyzes the differences amongst the facilities in terms of the patients' race, income, and level of education. ...Context 4
... at such centers may have provided these patients with access to other immune checkpoint inhibitor-based treatments through clinical trial enrollment. The abovementioned findings could, in part, be the reason for a higher proportion of AA patients receiving care in academic centers versus community centers (Table S2b) Mortality greatly varied based on melanoma type and presence or absence of metastasis. The presence of metastasis was associated with a greater than 80% mortality across all groups of melanomas (Table S4a,b). ...Citations
... Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, accounting for approximately 3.8% of all melanomas (predominantly in the Caucasian population) [1], and whose development may be influenced by genetic ancestry [2]. Although rare, its prognosis is often poor, with a high propensity for liver metastasis and limited effective therapeutic options (reviewed in [3][4][5]). ...
Uveal melanoma (UM), a distinct subtype of melanoma, presents unique challenges in its clinical management due to its complex molecular landscape and tendency for liver metastasis. This review highlights recent advancements in understanding the molecular pathogenesis, genetic alterations, and immune microenvironment of UM, with a focus on pivotal genes, such as GNAQ/11, BAP1, and CYSLTR2, and delves into the distinctive genetic and chromosomal classifications of UM, emphasizing the role of mutations and chromosomal rearrangements in disease progression and metastatic risk. Novel diagnostic biomarkers, including circulating tumor cells, DNA and extracellular vesicles, are discussed, offering potential non-invasive approaches for early detection and monitoring. It also explores emerging prognostic markers and their implications for patient stratification and personalized treatment strategies. Therapeutic approaches, including histone deacetylase inhibitors, MAPK pathway inhibitors, and emerging trends and concepts like CAR T-cell therapy, are evaluated for their efficacy in UM treatment. This review identifies challenges in UM research, such as the limited treatment options for metastatic UM and the need for improved prognostic tools, and suggests future directions, including the discovery of novel therapeutic targets, immunotherapeutic strategies, and advanced drug delivery systems. The review concludes by emphasizing the importance of continued research and innovation in addressing the unique challenges of UM to improve patient outcomes and develop more effective treatment strategies.
... Misdiagnosis can be highly problematic since these lesions are also difficult to diagnose clinically, and one major study examining the national cancer database from January 2004 to December 2015 found that 35% of desmoplastic melanoma (DM) cases had a Breslow depth > 4 mm at the time of diagnosis. 1 This is in stark contrast to conventional melanomas in which <4% were > 4 mm at the time of diagnosis. 2 Hence, underdiagnosis may result in inadequate treatment of a deep melanoma with catastrophic results. ...
Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant (P<0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.
... It is hypothesized that access to specialized therapies and enhanced care logistics at academic medical centers could be contributors to improved survival. 26,27 There are several limitations to this study. The NCDB is limited to Commission on Cancer accredited facilities, which covers approximately 75% of new cancer cases in the U.S. Thus, a significant fraction of hospitals may be underrepresented in this data due to selection bias, particularly against rural critical access hospitals. ...
BACKGROUND: Kaposi sarcoma (KS) is a cutaneous and mucous membrane tumor caused by human/Kaposi sarcoma herpesvirus 8 (HHV-8), typically seen in immunocompromised patients, including those with HIV/AIDS. Patients from traditionally underserved and underrepresented (URM) populations have disparate survival outcomes across malignancies, however the effects of socioeconomic and demographic factors on survival have not been described on a large scale in KS. METHODS: KS patients diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB). Overall survival (OS) was analyzed using Kaplan Meier and adjusted Cox regression methods, and repeated in a propensity score matched cohort, where White patients were matched to Black patients 1:1 for demographic factors and comorbidities. RESULTS: For the 4,034 identified patients, advanced age, Black race, HIV-positive status, and Charlson-Deyo score ≥1 were independently associated with decreased OS. Survival benefit was seen with Spanish/Hispanic ethnicity, private insurance, residence in areas of high educational attainment, and treatment at academic centers. Black patients had median survival of 99 months (95% confidence interval [CI] 73-124 months) compared to White patients (140 months, 95% CI 122-158 months) (p<0.001). Following propensity score matching, Black patients continued to have poorer OS compared to White patients (119 months versus 136 months, p=0.045). CONCLUSION: We describe the impact of socioeconomic factors and race on survival in KS, finding significantly reduced survival in Black patients, which persisted after controlling for covariates. These results highlight the need for directed efforts promoting equitable outcomes for underrepresented minorities.
... Consistent with our findings, other studies have shown that treatment with surgical excision for localized disease is associated with a higher expected overall survival [48]. Similarly, clinical guidelines dictate that radiation and cytotoxic chemotherapy treatment should be reserved for those requiring palliative treatment or for patients that developed resistance to immunotherapy drugs due to the low response rate seen with these agents for the treatment of metastatic CM [19,49]. ...
The incidence of cutaneous melanoma is rising, and Melanoma related deaths are highest among people aged 65–74. Herein, we aim to understand the impact of novel and established melanoma treatment methods on CM related mortality and all-cause mortality. We further compared these effects among Hispanic and non-Hispanic Whites (NHW).
The data was extracted from the Texas Cancer Registry from 2007 to 2017. A Cox Proportional Hazard regression analysis was performed to assess treatment effect on melanoma mortality and all-cause mortality, with race-ethnicity as an effect modifier.
A higher percentage of Hispanic patients presented with CM-related mortality (22.11%) compared to NHW patients (14.39%). In both the Hispanic and NHW, post-diagnosis radiation (HR = 1.610, 95% CI 0.984–2.634, HR = 2.348, 95% CI 2.082–2.648, respectively), post-diagnosis chemotherapy (HR = 1.899, 95% CI 1.085–3.322, HR = 2.035, 95% CI 1.664–2.489, respectively), and post-diagnosis immunotherapy (HR = 2.100, 95% CI 1.338–3.296, HR = 2.402, 95% CI 2.100–2.748) are each associated with an increased risk in CM-related mortality. Similar results were seen with post-diagnosis radiation (Hispanic HR = 1.640, 95% CI 1.121–2.400, NHW HR = 1.800, 95% CI 1.644–1.971), post-diagnostic chemotherapy (Hispanic HR = 1.457, 95% CI 0.898–2.364, NHW HR = 1.592, 95% CI 1.356–1.869), and post-diagnosis immunotherapy (Hispanic HR = 2.140, 95% CI 1.494–3.065, NHW HR = 2.190, 95% CI 1.969–2.435) with respect to all-cause mortality. Post-diagnosis surgery (HR = 0.581, 95% CI 0.395–0.856, HR = 0.622, 95% CI 0.571–0.678) had the opposite effect in CM-related mortality for Hispanics and NHWs respectively.
Our results propose differences in all-cause and CM-only related mortality with separate treatment modalities, particularly with chemotherapy, radiation therapy and immunotherapy. In addition, this retrospective cohort study showed that health disparities exist in the Hispanic Medicare population of Texas with CM.
... Melanoma is a fatal and aggressive tumor, as it is associated with poor prognosis in patients with advanced or metastatic disease [1][2][3][4]. Over the past decade, the incidence of occurrence melanoma has increased every year [5][6][7][8]. ...
Background
Recent studies have shown that circulating microRNAs (miRNAs) can be used as diagnostic biomarkers for melanoma. This study aimed to evaluate the diagnostic value of circulating miRNAs for melanoma.
Methods
A comprehensive literature search was conducted and the quality of the included literature was evaluated using QUADAS-2 (Quality Assessment for diagnostic accuracy studies), and the diagnostic accuracy was assessed by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). We used Deeks’ funnel plot to evaluate publication bias.
Results
The meta-analysis included 10 articles covering 16 studies, and the results showed that circulating miRNAs provide high diagnostic accuracy for melanoma. The overall pooled sensitivity was 0.87 (95% CI: 0.82–0.91), specificity was 0.81 (95% CI: 0.77–0.85), PLR was 4.6 (95% CI: 3.7–5.8), NLR was 0.16 (95% CI: 0.11–0.23), DOR was 29 (95% CI: 18–49), and AUC was 0.90 (95% CI: 0.87–0.92), respectively. Subgroup analysis showed better diagnostic value in miRNA clusters, European population, plasma miRNAs, and upregulated miRNAs compared to other subgroups.
Conclusions
The results indicated that circulating microRNAs can be used as a non-invasive biomarker for the diagnosis of melanoma.
... Skin cancer is the most common cancer and comprises both non-melanoma and melanoma skin cancers, whose incidence has been increasing constantly over the past decades. Skin cancers that are detected at early, non-metastatic stages are curable by surgical resection with a 5-year relative survival of 99.4% for localized melanoma and basal cell carcinoma [1]. Nevertheless, for metastatic melanoma disease, the 5-year survival rate drops to about 29.8% [1]. ...
... Skin cancers that are detected at early, non-metastatic stages are curable by surgical resection with a 5-year relative survival of 99.4% for localized melanoma and basal cell carcinoma [1]. Nevertheless, for metastatic melanoma disease, the 5-year survival rate drops to about 29.8% [1]. Therefore, there is a pressing need to identify biomarkers for the early detection of skin cancers at the earliest stages. ...
Introduction:
Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy.
Areas covered:
In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers.
Expert opinion:
Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings.
Simple Summary
Cutaneous melanoma, a fatal and aggressive tumor, has witnessed a transformative shift in its clinical management over the past decade with the advent of anti-programmed cell death 1 (PD1) and anti-cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) immunotherapies, as well as targeted therapies. Current standard monitoring methods, such as imaging scans, have limitations, necessitating the exploration of alternative biomarkers. Circulating tumor DNA emerges as a promising blood-based biomarker for precise clinical decisions.
Abstract
Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration of alternative biomarkers. This review comprehensively explores the role of circulating tumor DNA (ctDNA) in advanced melanoma, covering technical aspects, detection methods, and its prognostic and predictive value. Recent findings underscore ctDNA’s potential applications and implications in clinical practice. This review emphasizes the need for precise and dynamic biomarkers in melanoma care, positioning ctDNA as a promising blood-based tool for prognosis, treatment response, and resistance mechanisms. The technical nuances of ctDNA detection, association with melanoma mutations, and its role in guiding therapeutic decisions for immunotherapy and targeted therapy underscore its multifaceted utility, marking a paradigm shift in clinical decision-making and offering a promising trajectory for personalized and informed care in advanced melanoma.
Introduction
Melanoma guidelines stem largely from data on non‐Hispanic White (NHW) patients. We aimed to identify features of melanoma within non‐Hispanic Black (NHB) patients to inform strategies for earlier detection and treatment.
Methods
From 2004 to 2019 Surveillance, Epidemiology, and End Results (SEER) data, we identified nonmetastatic melanoma patients with known TN category and race. Kaplan–Meier cancer‐specific survival (CSS) estimates and multivariable Cox proportional hazard modeling analyses were performed.
Results
Of 492 597 patients, 1499 (0.3%) were NHB, who were younger (21% vs. 17% age <50) and more commonly female (54% vs. 41%) than NHW, both p < 0.0005. For NHBs, lower extremity was the most common site (52% vs. 15% for NHWs, p < 0.0001), T category was higher (55% Tis–T1 vs. 82%; 27% T3–T4 vs. 8%, p < 0.0001) and stage at presentation was higher (19% Stage III, vs. 6%, p < 0.0001). Within the NHB cohort, males were older, and more often node‐positive than females. Five‐year Stage III CSS was 42% for NHB males versus 71% for females, adjusting for age and clinical nodal status (hazard ratio 2.48).
Conclusions
NHB melanoma patients presented with distinct tumor characteristics. NHB males with Stage III disease had inferior CSS. Focus on this high‐risk patient cohort to promote earlier detection and treatment may improve outcomes.
Background
Immunotherapy agents are approved for adjuvant treatment of stage III melanoma; however, evidence for survival benefit in early stage III disease is lacking. Current guidelines for adjuvant immunotherapy utilization in stage IIIA rely on clinician judgment, creating an opportunity for significant variation in prescribing patterns. This study aimed to characterize current immunotherapy practice variations and to compare patient outcomes for different prescribing practices in stage IIIA melanoma.
Study design
Patients with melanoma diagnosed from 2015-2019 that met American Joint Committee on Cancer 8th edition criteria for stage IIIA and underwent resection were identified in the National Cancer Database. Multiple imputation by chained equations replaced missing values. Factors associated with receipt of adjuvant immunotherapy were identified. Multivariable Cox proportional hazards regression compared overall survival across groups.
Results
Of 4,432 patients included in the study, 34% received adjuvant immunotherapy. Patients had lower risk-adjusted odds of receiving immunotherapy if they were treated at an academic center (OR=0.48, 95%CI=0.33-0.72, p<0.001 vs. community facility) or at a high-volume center (OR=0.69, 0.56-0.84, p<0.001 vs. low-volume). Immunotherapy receipt was not associated with risk-adjusted survival (p=0.095). Moreover, patients treated at high-volume centers experienced longer overall risk-adjusted survival than those treated at low-volume centers (HR=0.52, 0.29-0.93, p=0.030). Risk-adjusted survival trended toward being longer at academic centers than at community centers, but the difference was not statistically significant.
Conclusion
Academic and high-volume centers utilize significantly less adjuvant immunotherapy in stage IIIA melanoma than community and low-volume centers without compromise in overall survival. These findings suggest that this population may benefit from more judicious immunotherapy utilization.
Background:
Protracted times to diagnosis of cancer can lead to increased patient anxiety, and in some cases, disease progression and worse outcomes. This study assessed the time to diagnosis for melanoma, and its variability, according to patient-, disease-, and system-level factors.
Methods:
This is a descriptive, cross-sectional study in Ontario, Canada from 2007-2019. We used administrative health data to measure the diagnostic interval (DI)-and its two subintervals-the primary care subinterval (PCI) and specialist care subinterval (SCI). Multivariable quantile regression was used.
Results:
There were 33,371 melanoma patients. The median DI was 36 days (interquartile range [IQR]: 8-85 days), median PCI 22 days (IQR: 6-54 days), and median SCI 6 days (IQR: 1-42 days). Increasing comorbidity was associated with increasing DI. Residents in the most deprived neighbourhoods and those in rural areas experienced shorter DIs and PCIs, but no differences in SCI. There was substantial variation in the DI and SCI across health regions, but limited differences in the PCI. Finally, patients with a history of non-melanoma skin cancer, and those previously established with a dermatologist experienced significantly longer DI, PCI, and SCI.
Discussion:
This study found variability in the melanoma DI, notably by system-level factors.
