Melanoma Survival Research Articles

Rural Melanoma Patients Have Less Surgery and Higher Melanoma-Specific Mortality.

Melanoma causes most skin cancer-related deaths, and disparities in mortality persist. Rural communities, compared to urban, face higher levels of poverty and more barriers to care, leading to higher stage at presentation and shorter survival in melanoma. To further evaluate these disparities, we sought to assess the association between rurality and melanoma cause-specific mortality and receipt of recommended surgery in a national cohort. Patients with primary non-ocular, cutaneous melanoma from the SEER database, 2000-2017, were included. Outcomes included melanoma-specific survival and receipt of recommended surgery. Rurality was based on Rural-Urban Continuum Codes. Variables included age, sex, race, ethnicity, income, and stage. Multivariate regression models assessed the effect of rurality on survival and receipt of recommended surgery. 103,606 patients diagnosed with non-ocular cutaneous primary melanoma met criteria during this period. 93.3% (n = 96620) were in urban areas and 6.7% (n = 6986) were in rural areas. On multivariate regression controlling for age, sex, race, ethnicity, and stage patients living in a rural area were less likely to receive recommended surgery (aOR .52, 95% CI: .29-.90, P = .02) and had increased hazard of melanoma-specific mortality (aHR 1.19, 95% CI: 1.02-1.40, P = .03) even after additionally controlling for surgery receipt. Using a large national cohort, our study found that rural patients were less likely to receive recommended surgery and had shorter melanoma cause-specific survival. Our findings highlight the importance of access to cancer care in rural areas and how this ultimately effects survival for these patients.

Dermatologic surgeons' approaches to acral lentiginous melanoma: a survey of the American College of Mohs Surgery.

Acral lentiginous melanoma (ALM) is a subtype of melanoma that primarily affects ethnic minorities and is associated with poor outcomes. Racial inequalities in melanoma survival, particularly between Blacks and Whites, have been well documented in the literature. There are limited data on the role of surgical approach to ALM and its contribution to the existing disparities in ALM survival. Thus, this study aimed to investigate the role of surgical approach to ALM among Mohs surgeons. The survey was distributed to members of the American College of Mohs Surgery (ACMS), with 43 physicians completing the survey. The results showed that there was no consensus among Mohs surgeons regarding the surgical approach for ALM, even for advanced stages. 74% respondents performed complete circumferential peripheral and deep margin assessment (CCPDMA) for ALM, including Mohs micrographic surgery (MMS) or en face staged excision. However, barriers such as limited training, low comfort operating on acral sites, and inadequate access to specialized biopsies were reported. Treatment recommendations varied widely regardless of the ALM stage, with no significant differences based on exposure to ALM during training, practice setting, or percent of skin of color patients served. These findings highlight the lack of guidelines and the need for more data on outcomes to support optimal management of ALM. The study emphasizes the importance of addressing healthcare disparities and improving survival outcomes, particularly for ethnic minorities affected by ALM. Consensus guidelines could help standardize treatment approaches and potentially reduce disparities in ALM management.

Prognostic value and immunological role of cathepsin S gene in pan‑cancer.

The cathepsin S (CTSS) gene encodes a lysine cysteine protease and serves an important role in the development of autoimmune diseases, inflammation and nervous system diseases. Furthermore, CTSS is implicated in tumor invasion and metastasis by the induction of tumor angiogenesis and the degradation of the tumor extracellular matrix. Nevertheless, the precise impact of CTSS on predicting pan-cancer prognosis and its influence on the tumor microenvironment and immune infiltration in human cancers remains unknown. This present study employed a comprehensive array of bioinformatic methods to evaluate the expression of CTSS and its associations with prognosis, clinicopathological characteristics, tumor microenvironment, tumor immune infiltration, tumor mutational burden and microsatellite instability across numerous cancer types. The current study demonstrated abnormal expression and distinct genomic alteration profiles of CTSS in many of the cancers tested. Furthermore, CTSS expression exhibited close associations with the prognosis of numerous cancers. High CTSS expression was significantly associated with better overall survival and disease-specific survival in bladder urothelial carcinoma (BLCA) and skin cutaneous melanoma (SKCM) but worse outcomes in brain lower grade glioma (LGG) and uveal melanoma (UVM). Moreover, CTSS demonstrated significant correlations with tumor mutational burden and microsatellite instability in 8 and 12 cancer types respectively, as well as different responses in immunotherapy sub-cohorts, especially in melanoma and bladder cancers. CTSS expression showed a positive correlation with stromal and immune cell scores in the four aforementioned cancers. Moreover, CTSS expression was correlated with the number of infiltrating CD8+ T cells, CD4+ T cells and macrophages. Conversely, CTSS was negatively associated with resting Mast cells, resting NK cells and resting memory CD4+ T cell infiltration in BLCA, SKCM and kidney renal clear cell carcinoma (KIRC). Furthermore, CTSS expression was correlated with immune-related gene expression, notably PDCD1, LAG3, PDCD1 and TIGIT in BLCA, KIRC, SKCM, LGG and UVM. Functional enrichment analysis suggested that CTSS could drive a dynamic adjustment of biological functions and pathways in BLCA, SKCM, LGG and UVM, including immune response regulating signaling pathways, regulation of lymphocyte activation and T cell receptor singling pathways. The current study suggested that CTSS could be an essential biomarker for prognosis and immune infiltration features in multiple cancers.

PP491 Integrating single-cell and bulk RNA-seq data to identify metastasis-related T cell marker signature using machine learning algorithms to predict the overall survival of malignant melanoma

PP491 Integrating single-cell and bulk RNA-seq data to identify metastasis-related T cell marker signature using machine learning algorithms to predict the overall survival of malignant melanoma

Abstract B051: Immunotherapy treatment disparities: A TCR analysis of patients with cutaneous melanoma

Abstract Abstract Background: As the deadliest form of skin cancer, advanced-stage melanoma is a devastating disease. Encouragingly, after the introduction of systemic immunotherapy, the overall survival of metastatic melanoma has improved drastically. Immunotherapy is showing superior survival outcomes for patients with advanced stage melanoma, but access to novel immunotherapeutic drugs is not universal for all patients. Herein, we examined the association between various sociodemographic and economic factors and the likelihood of using immunotherapy for the treatment of melanoma in the state of Texas. Patients and Methods: In this retrospective cohort study, data from the Texas Cancer Registry for the years 2011-2018 was analyzed. The study population included 35963 patients, 18 years and older, diagnosed with cutaneous melanoma. As a primary study outcome, multivariable regression analysis was done to evaluate the association between patient characteristics and likelihood of receipt of immunotherapy. As secondary outcomes, the association between sociodemographic factors and likelihood of presentation with metastasis at diagnosis was examined. Finally, subgroup analysis evaluated general trends between Hispanic and non-Hispanic patients with melanoma. Results: A total of 933 patients underwent immunotherapy. Having metastasis at diagnosis was strongly associated with higher odds of receiving immunotherapy (penalized adjusted OR 28.690, 95% CI 23.470-34.350, p< .0001). Compared to having private insurance, patients were less likely to receive immunotherapy if they were uninsured, had Medicare, or had missing/unknown insurance status (penalized adjusted OR’s 0.700, 0.790, 0.130, p = 0.026, 0.027, and p < .0001 respectively). Hispanic ethnicity did not show a statistically significant association with likelihood of receipt of immunotherapy. Results from our multivariate model highlighted several factors associated with a higher likelihood of presenting with metastatic disease which included Hispanic ethnicity, black race, having no insurance, having Medicare, and belonging to the 10-20% and the 20-100% poverty level groups (p <0.05 for all). When compared to NHW’s, Hispanics with melanoma demonstrate a higher level of poverty, increased risk of metastasis at diagnosis, as well as higher likelihood of being uninsured and living in a border region (p < 0.001 for all). Conclusion: Immunotherapy has revolutionized the treatment of melanoma. As new immunotherapy drugs reach the market, disparities in utilization of immunotherapy are expected to increase. With this retrospective cohort study, we add to the growing body of evidence recognizing insurance status as a barrier to treatment with immunotherapy. Dermatologic health disparities affecting the Hispanic population underscore the importance of targeted interventions to overcome community level barriers to melanoma diagnosis and care. Finally, this study highlights the need to further evaluate different insurance types and their effect on receipt of immunotherapy. Citation Format: Fabiola G. Ramirez, Luis Alvarado, Alok Dwivedi, Jessica Chacon. Immunotherapy treatment disparities: A TCR analysis of patients with cutaneous melanoma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B051.

Educational Intervention and Melanoma Prognosis in Black People.

A systematic search was conducted on the PubMed database using the keywords "education," "melanoma," and "African Americans." The results were filtered to include studies published within the last decade that focused on melanoma diagnosis, risk, or outcomes. These selected studies included African Americans, non-Hispanic Black individuals, or those with darker skin tones and compared them with educational interventions or non-Hispanic White groups. The studies showedan overall positive impact of targeted educational initiatives on using sun-protective behaviors, health education, and self-efficacy related to melanoma. Notably, interventions proven to be effective for non-Hispanic White populations also demonstrated efficacy in other racial groups, including non-Hispanic Blacks. It was observed that non-Hispanic Blacks exhibited an overall reduced level of concern regarding melanoma, partly due to its lower incidence within this demographic.Furthermore, these studies focussed on the disparities in melanoma incidence and survival rates among different racial groups. Non-Hispanic Black individuals were found to have a higher incidence of melanoma and lower survival rates compared to non-Hispanic White individuals. Collectively, the studies evaluating melanoma educational interventions for darker skin tones yield promising results for improving melanoma prognosis in Black communities. They underscore the importance of addressing racial disparities in melanoma awareness, diagnosis, and treatments. These studies also highlighted the barriers to sun protection behaviors, such as cost, limited awareness, and misconceptions, particularly prevalent among ethnic communities and youth. The use of melanoma photographs specifically tailored to darker skin tones in outreach efforts to enhance identification, self-examination, and early detection should be considered to improve melanoma prognosis similar to the non-White population.

Melanoma and CLL co-occurrence and survival: role of KC history

BackgroundSurvival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers.MethodsA retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case–control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups.ResultsA time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma.ConclusionsHistory of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis.

Pan-cancer analysis of the prognostic significance of ACKR2 expression and the related genetic/epigenetic dysregulations

ABSTRACT Objective ACKR2 is a scavenger for most inflammation-related CC chemokines. This study aimed to assess the pan-cancer prognostic significance of ACKR2 and the genetic and epigenetic mechanisms underlying its dysregulation. Methods Pan-cancer data from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and The Genotype-Tissue Expression (GTEx) were integrated and analyzed. Results ACKR2 is consistently associated with favorable progression-free interval (PFI) and overall survival (OS) in TCGA-uveal melanoma (UVM) and TCGA-liver hepatocellular carcinoma (LIHC). ACKR2 is negatively correlated with the expression of CCL1, CCL4, CCL5, CXCL8, CCL17, and CCL20 in TCGA-UVM and TCGA-LIHC. The group with gene copy gain had significantly higher ACKR2 expression than those with loss. The lower ACKR2 expression groups were associated with a significantly higher ratio of BAP1 mutations. In addition, ACKR2 was negatively corrected with DNMT1 expression but was positively corrected with ZC3H13, an m6A writer gene and NSUN3, an RNA m5C writer gene. Conclusions ACKR2 expression was associated with favorable prognosis in patients with uveal melanoma and hepatocellular carcinoma. ACKR2 dysregulation might be an accumulated result of gene copy number alterations, transcriptional disruption, and RNA modifications.

Surveillance for Metastasis in High-Risk Uveal Melanoma Patients: Standard versus Enhanced Protocols.

to evaluate the effectiveness of enhanced surveillance protocols (EP) utilizing high frequency (HF) or enhanced modality (EM) compared to the standard protocol (SP) in detecting metastasis and determining their impact on overall survival (OS) in high-risk uveal melanoma (UM) patients. A total of 87 consecutive patients with Class 2 (high risk) primary UM were enrolled, with negative baseline systemic staging. The patients underwent systemic surveillance with either SP (hepatic ultrasonography [US] every 6 months) or EP (either HF [US every 3 months] or EM [incorporation hepatic computed tomography/magnetic resonance imaging]) following informed discussion. The main outcome measures were largest diameter of largest hepatic metastasis (LDLM), number of hepatic metastatic lesions, time to detection of metastasis (TDM), and OS. This study revealed significant differences in LDLM between surveillance protocols, with the use of EP detecting smaller metastatic lesions (HF, EM, and SP were 1.5 cm, 1.6 cm, and 6.1 cm, respectively). Patients on the EM protocol had a lower 24-month cumulative incidence of >3 cm metastasis (3.5% EM vs. 39% SP; p = 0.021), while those on the HF protocol had a higher 24-month cumulative incidence of ≤3 cm metastasis compared to SP (31% HF vs. 10% SP; p = 0.017). Hazard of death following metastasis was significantly reduced in the EP (HR: 0.25; 95% CI: 0.07, 0.84), HF (HR: 0.23; 95% CI: 0.06, 0.84), and EM (HR: 0.11; 95% CI: 0.02, 0.5) groups compared to SP. However, TDM and OS did not significantly differ between protocols. Enhanced surveillance protocols improved early detection of hepatic metastasis in UM patients but did not translate into a survival advantage in our study cohort. However, early detection of metastasis in patients receiving liver-directed therapies may lead to improved overall survival.

Spatial Proximity and Relative Distribution of Tumor-Infiltrating Lymphocytes and Macrophages Predict Survival in Melanoma

Tumor microenvironment plays a crucial role in primary cutaneous melanoma (CM) progression. Although the role of tumor-infiltrating lymphocyte (TIL) density has been known for a long time, its spatial distribution and impact with or without tumor-associated macrophages (TAMs) remain controversial. Herein, we investigated spatial proximity between tumor cells and immune cells in 113 primary CM and its correlation with disease-free (DFS) and overall survival (OS). The study cohort included clinical stage II (n = 79) and stage III (n = 34) primary CM with a Breslow thickness of >2 mm (with a median age of 64 years, including 72 men and 41 women). In univariate models, patients with SOX10+ melanoma cells with high proximity to CD8+ TILs in a 20 μm radius showed longer DFS (hazard ratio [HR], 0.58; 95% CI, 0.36–0.93; P = .025) and OS (HR, 0.55; 95% CI, 0.32–0.92; P = .023). Furthermore, at multivariate combined analysis, patients with SOX10+ melanoma cells with high proximity to CD8+ TILs or low proximity to CD163+ TAMs in a 20 μm radius showed an increased OS (aHR, 0.37; 95% CI, 0.14–0.96; P = .04) compared with melanoma patients with low proximity to CD8+ TILs or high proximity to CD163+ TAMs. In a subgroup analysis including 92 patients, a significant negative impact on DFS (aHR, 4.49; 95% CI, 1.73–11.64; P = .002) and OS (aHR, 3.97; 95% CI, 1.37–11.49; P = .01) was observed in sentinel lymph node (SLN)-negative patients with a high proximity of CD163+ TAMs to CD8+ TILs. These findings could help identify high-risk patients in the context of thick melanoma and a negative SLN. Our study suggests the importance of quantifying not only the density of immune cells but also the individual and combined relative spatial distributions of tumor cells and immune cells for clinical outcomes in SLN-negative primary CM patients.

Do age at diagnosis, tumour thickness and tumour site explain sex differences in melanoma survival? A causal mediation analysis using cancer registry data.

Women diagnosed with melanoma have better survival than men, but little is known about potential intervention targets to reduce this survival gap by sex. We conducted a population-based study using Victorian Cancer Registry data including 5833 women and 6780 men aged 15 to 70 years when diagnosed with first primary melanoma between 2007 and 2015. Deaths to the end of 2020 were identified through linkage to the Victorian and national death registries. We estimated the effect of age at diagnosis, tumour thickness and tumour site on reducing the melanoma-specific survival gap by sex (ie, interventional indirect effects [IIEs]) on risk difference (RD) scale. Compared to women, there were 211 (95% CI: 145-278) additional deaths per 10 000 in men within 5 years following diagnosis. We estimated that 44% of this gap would be reduced by a hypothetical intervention shifting the distribution of melanoma thickness in men to be the same as that observed for women (IIEthickness RD 93 [95% CI: 75-118] per 10 000) and 20% by an intervention on tumour site (head and neck/trunk vs upper limb/lower limb; IIEsite RD 42 [95% CI: 15-72] per 10 000), while an intervention on age at diagnosis would have a negligible effect. Tumour thickness, tumour site and age at diagnosis mediated 65% of the effect of sex on 5-year melanoma survival in Victoria. Of these factors, tumour thickness had the most considerable mediating effect, suggesting that effective promotion of earlier detection of melanoma in men could potentially nearly halve the gap in melanoma-specific survival by sex.

Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies

ABSTRACT Lymphocyte-activation gene-3 (LAG-3), an immune checkpoint receptor, negatively regulates T-cell function and facilitates immune escape of tumors. Dual inhibition of LAG-3 and programmed cell death receptor-1 (PD-1) significantly improved progression-free survival (PFS) in metastatic melanoma patients compared to anti-PD-1 therapy alone. Investigating the utility of LAG-3 expression as a biomarker of response to anti-LAG-3 + anti-PD-1 immunotherapy is of great clinical relevance. This study sought to evaluate the association between baseline LAG-3 expression and clinical outcomes following anti-LAG-3 and anti-PD-1-based immunotherapy in metastatic melanoma. LAG-3 immunohistochemistry (clone D2G4O) was performed on pre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 53 patients treated with combination anti-LAG-3 + anti-PD-1-based therapies. Eleven patients had received prior anti-PD-1-based treatment. Patients were categorized as responders (complete/partial response; n = 36) or non-responders (stable/progressive disease; n = 17) based on the Response Evaluation Criteria in Solid Tumours (RECIST). Tumor-infiltrating lymphocytes (TILs) were scored on hematoxylin and eosin-stained sections. LAG-3 expression was observed in 81% of patients, with staining in TILs and dendritic cells. Responders displayed significantly higher proportions of LAG-3+ cells compared to non-responders (P = .0210). LAG-3 expression positively correlated with TIL score (P < .01). There were no significant differences in LAG-3 expression between different sites of metastases (P > .05). Patients with ≥ 1% LAG-3+ cells in their tumors had significantly longer PFS compared to patients with < 1% LAG-3 expression (P = .0037). No significant difference was observed in overall survival between the two groups (P = .1417). Therefore, the assessment of LAG-3 expression via IHC warrants further evaluation to determine its role as a predictive marker of response and survival in metastatic melanoma.

1157P Corticosteroids and second-line immunosuppressants for immune-related adverse events and melanoma survival

1157P Corticosteroids and second-line immunosuppressants for immune-related adverse events and melanoma survival

The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas.

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

OUTCOMES OF STEREOTACTIC RADIOSURGERY/RADIOTHERAPY (SRST) IN MALIGNANT MELANOMA WITH CRANIAL METASTASES - THE WESSEX EXPERIENCE

Abstract AIMS To assess overall survival in malignant melanoma with cranial metastases following stereotactic radio- surgery/radiotherapy (SRST). METHOD Patients with metastatic melanoma who received SRST for their cranial metastases at the Wessex Neuro- Oncology Unit were evaluated between January 2017 and January 2023. Subtype analysis based on BRAF mutation was also performed. Their overall survival (OS) was plotted using Kaplan-Meier graph. RESULTS 121 patients were identified. The mean age at referral was 62 years (range 30-90). 50 patients had a BRAF mutation while 71 were BRAF wild type. This is a heterogenous cohort of patients, ranging from cranial-only disease to widespread disease, receiving one to two lines of systemic treatment. The median OS in patients with malignant melanoma with cranial metastases following SRST is 15 months (similar in both BRAF mutant and BRAF wildtype subgroups). The 3-year survival rate is 22.8% (BRAF mutant – 27.3%, BRAF wildtype - 20.3%). There is a small group of patients (28%) that died within six months of SRST. CONCLUSIONS Limitations were the small number of patients, short follow up period and heterogeneity in terms of systemic therapy. Our experience reveals in malignant melanoma, the median OS is 15 months after SRST to their cranial metastases. We found that BRAF mutation is non-discriminatory when predicting response to SRST and not the sole factor in predicting OS. A small cohort did not benefit from SRST as they survived for 6 months or less. Further analysis of this subgroup is needed to improve patient selection and treatment personalisation.

Clinicopathologic features, delayed diagnosis, and survival in amelanotic acral melanoma: A comparative study with pigmented melanoma

Clinicopathologic features, delayed diagnosis, and survival in amelanotic acral melanoma: A comparative study with pigmented melanoma

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden.

CCDC50 promotes tumor growth through regulation of lysosome homeostasis.

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 suppresses tumor growth and lung metastasis, and enhances the effect of BRAFV600E inhibition. Thus, we demonstrate critical roles of CCDC50-mediated clearance of damaged lysosomes in supporting tumor growth, hereby identifying a potential therapeutic target of melanoma.

42558 Disparities in Melanoma Survival in Asian American and Pacific Islander Patients

42558 Disparities in Melanoma Survival in Asian American and Pacific Islander Patients

Predictive accuracy of risk prediction models for recurrence, metastasis and survival for early-stage cutaneous melanoma: a systematic review

ObjectivesTo identify prognostic models for melanoma survival, recurrence and metastasis among American Joint Committee on Cancer stage I and II patients postsurgery; and evaluate model performance, including overall survival (OS)...