Cutaneous Melanoma Patients Research Articles

Recent Developments of Circulating Tumor Cell Analysis for Monitoring Cutaneous Melanoma Patients.

Simple SummaryCirculating tumor cells (CTCs) originating from cutaneous melanoma patients have been studied for several decades as surrogates for real-time clinical status and disease outcomes. Here, we will review clinical studies from the last 15 years that assessed CTCs and disease outcomes for melanoma patients. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, to address tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single-center trials. Recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients.Circulating tumor cells (CTCs) have been studied using multiple technical approaches for interrogating various cancers, as they allow for the real-time assessment of tumor progression, disease recurrence, treatment response, and tumor molecular profiling without the need for a tumor tissue biopsy. Here, we will review studies from the last 15 years on the assessment of CTCs in cutaneous melanoma patients in relation to different clinical outcomes. The focus will be on CTC detection in blood samples obtained from cutaneous melanoma patients of different clinical stages and treatments utilizing multiple platforms. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single- center trials. The recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic aberration profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients. The molecular studies on melanoma CTCs have provided and may set standards for other solid tumor CTC analyses.

Pan-immune-inflammation value independently predicts disease recurrence in patients with Merkel cell carcinoma

PurposeWe aimed to determine whether the pan-immune-inflammation value (PIV) of patients with Merkel cell carcinoma (MCC) at primary diagnosis differs from controls and whether it is associated with disease stage and outcome.MethodsIn this retrospective study, we recruited MCC patients with stage I–III. PIV was calculated from absolute complete blood cell counts obtained within one week at MCC diagnosis as follows: [neutrophils (103/mm3) × platelets (103/mm3) × monocytes (103/mm3)]/lymphocytes (103/mm3). As controls, we studied age–gender-matched cutaneous melanoma (CM, stage I–III) patients and healthy controls (HC). Univariate and multivariate statistics were used.ResultsThe median PIV in MCC patients was significantly increased compared to both CM patients as well as healthy controls. PIV of MCC patients in stage II and III was significantly higher compared to stage I patients. ROC analysis revealed that MCC recurrence was significantly associated with a PIV greater than 372 [p < 0.0001, Youden index 0.58; hazard ratio: 4 (95% confidence interval: 1.7 to 9.2)]. In multivariate analysis, only a PIV greater than 372 and higher MCC stage were determined as independent predictors for disease recurrence.ConclusionWe determined, for the first time, the prognostic ability of the promising blood-based biomarker PIV in MCC patients and observed that PIV is increased in MCC patients in dependence on disease stage and independently predicts MCC recurrence.

Sex Differences in Cutaneous Melanoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background:This study aims to provide a comprehensive overview of sex-related characteristics of cutaneous malignant melanoma (CMM), with special reference to its incidence, clinicopathological profile, overall survival, and treatment-related costs.Methods:This retrospective cohort study included all 1,279 CMM patients who were registered in 2015 in the Veneto Cancer Registry (a population-based registry including all 4,900,000 regional residents). The by-sex comparisons included tumor stage and site, histological subtype, and other clinical–pathological variables. A Cox regression analysis was used to test the association between sex and survival, adjusting for the main covariates. Treatment costs were calculated by linking patients with several administrative regional databases.Results:Age-specific incidence rates were significantly higher for men among people >50 years old. For men, the trunk was the most common primary site (59.3%), whereas for women the lower limbs (32.1%) were the most common primary site, followed by the trunk (31.8%), which was lower than for men (p < 0.001). At presentation, the frequency of early stage CMM was higher among women, who also featured a significantly lower risk of death (p = 0.016), after adjusting for covariates. Men also incurred higher costs for melanoma treatment in the first year after their diagnosis.Conclusions:Among younger adults, CMM was more common in women, whereas among older adults, it was more common in men. Sex also influences patients' histopathological characteristics at diagnosis. Women had better overall survival after adjusting for demographic, pathological, and clinical profiles. The costs of treatment were also lower for women with CMM.

Postoperative Radiotherapy for Cutaneous Melanoma in Patients at High Risk of Local-Regional Recurrence after Surgery Alone

We evaluated outcomes in 131 patients with cutaneous melanoma (median follow-up, 3.6 years) considered at high risk of recurrence after surgery alone treated with surgery and postoperative radiotherapy. Eligible patients had one or more of the following: recurrence after surgery, positive lymph nodes, extracapsular extension, incomplete regional node dissection, microscopically positive margins, gross residual disease, or in-transit metastases. 102 patients received hypofractionated radiotherapy and 29 had conventional fractionation. 10-year outcomes were: in-field local-regional control, 87%; local regional control, 72%; distant metastasis-free survival, 48%; cause-specific survival, 44%; and overall survival, 31%. Three patients experienced acute toxicities while 6 experienced late toxicities.

Identification of Potential Core Genes Between Primary and Metastatic Malignant Melanoma and Analysis of Their Immune Correlation.

PurposeTo identify the potential differential genes between primary and metastatic melanoma, screen out immune-related genes in core genes and analyze their immune correlation, thus searching for the early diagnostic biomarkers of cutaneous malignant melanoma (CMM) and the targets of curbing metastasis.Materials and MethodsWe analyzed two microarray datasets (GSE8401 and GSE46517) derived from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between primary and metastatic melanoma were screened out using the GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify the functions and pathways of DEGs. We analyzed protein–protein interaction of these DEGs based on the Search Tool for the Retrieval of Interacting Genes database and showed by Cytoscape software. In addition, the online Gene Expression Profiling Interactive Analysis tool (GEPIA) was used to analyze the prognostic value of hub genes expressed in metastatic melanoma patients. Immune-related genes in hub genes were screened and further analyzed.ResultsA total of 178 upregulated DEGs and 4 downregulated DEGs were identified. 23 terms and 4 pathways were confirmed related to metastatic melanoma. Ten hub genes with a high degree of connectivity were found. Overexpression of three hub genes (DSG1, FLG, PKP1) (P<0.01) was associated with metastasis and poor prognosis of CMM. Among them, the patients with overexpression of PKP1 suffered shorter survival. In addition, 2 immune-related genes (EGFR and CDH1) in hub genes were screened out and both of them were related to anti-tumor immunity, although their expression level did not affect the overall survival of CMM patients significantly.ConclusionOur study suggests that DSG1, FLG and PKP1 were overexpressed in metastatic melanoma compared with primary melanoma, and overexpression of these three genes was an unfavorable prognostic factor ifor CMM patients, which may indicate that they are associated with promoting metastasis of malignant melanoma. EGFR and CDH1 play a crucial role in anti-tumor immunity for CMM. Further research is needed to explore the value of these genes in the inhibition of metastasis and treatment of CMM.

The efficacy of 99mTc-rituximab as a tracer for sentinel lymph node biopsy in cutaneous melanoma patients.

BackgroundThe sentinel lymph node (SLN) status is a vital prognostic factor for malignant melanoma (MM) patients. There is increasing evidence that a radioactive agent, rather than its combination with blue dye, is sufficient for a SLN biopsy (SLNB). Thus, we discussed the efficacy of 99mTc-rituximab as a tracer in MM patients.MethodsA total of 502 consecutive patients with MM who underwent SLNB were enrolled in this study. All participants were peritumorally injected with 99mTc-rituximab before imaging, and scanned with single-photon emission computed tomography-computed tomography (SPECT-CT) to detect the number and location of the SLN. A gamma detection probe was employed to detect radioactive SLNs in operation. Follow up was conducted to observe whether nodal or distant recurrence occurred.ResultsThe SLNs were successfully imaged via SPECT-CT and harvested from all 502 participants. No drainage tube was indwelled and 32 (6.3%) participants experienced the following complications: seroma (n=26, 5.2%), wound infections or lymphangitis (n=6, 1.2%), sensory nerve injuries (n=4, 0.8%). There were 380 patients who were diagnosed as SLN-negative and 122 (24.2%) were SLN-positive. A total of 85 SLN-positive patients received complete lymph node dissection, and 28 (32.9%) had additional positive lymph nodes. During a median follow-up of 24 months, 28 participants were found to have a false negative (FN) SLN. The FN rate was 18.7%. A higher T stage was a predictive factor for FN [odds ratio (OR) 1.77; P<0.05]. There was no significant difference in the positive or FN rate between the acral and cutaneous groups.ConclusionsThe radiopharmaceutical 99mTc-rituximab could be employed as a simple and safe tracer in acral and cutaneous melanoma SLN biopsies.

CD96 as a Potential Diagnostic Biomarker and New Target for Skin Cutaneous Melanoma.

Skin cutaneous melanoma has high morbidity and mortality. Identification of reliable and quantitative melanoma biomarkers could facilitate an early diagnosis and improve survival and morbidity rates. CD96 has a significant role in adjusting immune function. Although the abnormal expression of CD96 has been reported to participate in carcinogenesis in many human types of cancer, the bioinformatics role of the CD96 in melanoma is unknown. Expression degrees and their underlying functions were first studied by this study. According to TCGA, GTEx, and gene expression profile interaction analysis dataset in this paper, compared with normal skin tissues, CD96 was expressed at higher levels in human cutaneous melanoma skin tissues. Meanwhile, we detected the relative CD96 expression levels by immunohistochemistry. Gene functional enrichment analyses were applied through cBioPortal database analysis. CD96 was clearly upregulated in skin cutaneous melanoma patients and carried out its effects through regulating several signaling pathways, containing the JAK-STAT, PI3K-Akt, and MAPK. Taken together, the analysis results indicated that CD96 could be used as a new clinical bioindicator as well as an underlying medicinal target for cutaneous melanoma.

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

ObjectiveTo demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.Methods and analysisRetrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating...

Melanoma in patients with mycosis fungoides

The development of both malignant neoplasms mycosis fungoides and cutaneous malignant melanoma is a rare condition; nevertheless, the literature describes both cases of the development of mycosis fungoides in patients with a primary diagnosis of melanoma and the detection of cutaneous malignant melanoma in patients with T-cell lymphomas of the skin. The question of the effect of previous therapy for mycosis fungoides on the risk of cutaneous malignant melanoma remains controversial. Currently, the world community is considering a possible pathogenetic relationship between these two oncopathologies. The clinical observations of the development of cutaneous malignant melanoma in 2 patients with mycosis fungoides presented in the article emphasize the importance of a thorough clinical and dermatoscopic examination of all pigmented formations for the timely detection of malignant melanocytic neoplasms, the presence of which radically affects the further choice of treatment tactics for patients.

Immune Checkpoint Inhibitor Treatment and Ophthalmologist Consultations in Patients with Malignant Melanoma or Lung Cancer-A Nationwide Cohort Study.

Simple SummaryImmune checkpoint inhibitors are increasingly being used for treating advanced malignant cutaneous melanoma and lung cancer. Immune-related side effects in multiple organs are common but the frequencies of ophthalmic side effects in national cohorts of unselected patients are undescribed. This study estimated frequencies of first-time ophthalmologist consultations and inflammatory conditions in consecutive patients with malignant melanoma or lung cancer treated with immune checkpoint inhibitors in Denmark from 2011–2018. The one-year risks of first-time consultation and ocular inflammation were 6% and 1%, respectively. These numbers were increased compared with patients with the same type of cancer who were not treated with immune checkpoint inhibitiors.Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. Results: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4–1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83–27.31) and men (4.87 (95% CI 1.79–13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29–2.34) and MM (HR 3.21 (95% CI 2.31–4.44). Conclusions: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI.

Silencing FYVE, RhoGEF, and PH domain containing 1 (FGD1) suppresses melanoma progression by inhibiting PI3K/AKT signaling pathway

ABSTRACT Cutaneous melanoma is the leading cause of death among skin cancers despite the availability of diverse treatments. FGD1 plays an important role in multiple cancers, but how it works in cutaneous melanoma has not been illustrated. Thus, this study was intended to investigate the roles of FGD1 and its underlying mechanisms in cutaneous melanoma. Bioinformatics tools and quantitative real-time polymerase chain reaction (qRT-PCR) were used to analyze the expression of FGD1 in cutaneous melanoma. After the knockdown of FGD1 in melanoma cells, the proliferation, migration, and invasion of cells were analyzed by cell counting kit-8 (CCK8) assay, colony formation assays and transwell assays. Western blot was used to check the expression of key factors in PI3K/AKT pathway. In addition, nude mice models were used to study the role of FGD1 in melanoma development and metastasis in vivo. The data demonstrated that FGD1 was up-regulated and predicted a poor clinical outcome for cutaneous melanoma patients. Knockdown of FGD1 inhibited melanoma cell proliferation, migration, and invasion. The expressions of p-PI3K and p-AKT were significantly decreased, while the expressions of PI3K and AKT showed no marked difference in the knockdown group. Meanwhile, knockdown of FGD1 suppressed the development of melanoma in vivo. This study suggested that knockdown of FGD1 could block melanoma formation and proliferation by inhibiting PI3K/AKT signaling pathway. FGD1 might be a promising therapeutic target for melanoma.

Identification of TNFAIP8 as an Immune-Related Biomarker Associated With Tumorigenesis and Prognosis in Cutaneous Melanoma Patients.

Tumor necrosis factor-α–induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which is associated with inflammation and tumorigenesis. The potential role of TNFAIP8 in a tumor immune microenvironment in skin cutaneous melanoma (SKCM) has not yet been investigated. The TNFAIP8 expression was evaluated via gene expression profiling interactive analysis (GEPIA). We also evaluated the influence of TNFAIP8 on overall survival via GEPIA and PrognoScan. After GO and KEGG pathway analyses, the correlation between the TNFAIP8 expression level and immune cells or gene markers of the immune infiltration level was explored by R-language. The result showed the TNFAIP8 expression was significantly reduced in SKCM in comparison with normal control. In SKCM, the TNFAIP8 expression in higher levels was associated with the better overall survival. The high expression of TNFAIP8 was positively correlated with the immune score and promoted immune cell infiltration in SKCM patients. TNFAIP8 can be a positive prognosis marker or new immunotherapy target in SKCM.

The diagnostic value of modified systemic \u0131nflammation score in predicting post-operative outcomes of cutaneous melanoma patients who underwent \u0131solated limb perfusion

BackgroundIn-transit metastasis is considered a locoregional disease in cutaneous melanoma (CM) patients. Isolated limb perfusion (ILP) is among the treatment options in selected cases. The aim of this study was to determine the success of pre- and post-perfusion mSIS values in predicting the potential complications and the prognosis of the disease by investigating the early and long-term results of mSIS values calculated before and after ILP in CM cases with in-transit metastases.Materials and methodsPatients who underwent ILP within the period from 2014 to 2020 in our department were retrospectively scanned. A total of 20 patients were found to undergo ILP. The scores obtained from modified inflammation score (mSIS) were formulated according to albumin (Alb) and lymphocyte to monocyte ratio (LMR) scores.ResultsThe mean follow-up time was 20.47 months. Complications requiring surgical intervention developed in three patients. According to the Wieberdink local toxicity classification, the majority (70%) of the patients were found to be grade II. Based on pre-perfusion mSIS values, 8 patients were classified as mSIS 0 while six patients were classified as mSIS 1 and 2. Based on post-perfusion mSIS values, 14 patients and one patient were classified as mSIS 2 (70%) and mSIS 0, respectively. Accordingly, univariate analysis showed that mSIS 1 and mSIS 2 were negative prognostic factors for mean survival in the pre-perfusion period (HR 0.162, 95% CI 0.036–0.729; p = 0.018 and HR: 0.223, 95% CI 0.049–1.019; p = 0.053) whereas albumin (Alb) and lymphocyte to monocyte ratio (LMR) were not independent prognostic factors for mean survival.ConclusionThe mSIS values calculated in the pre-perfusion period can give an opinion about the OS of the patients whereas post-perfusion mSIS values may predict potential surgical complications and local toxicities.

Clinicopathologic models predicting non-sentinel lymph node metastasis in cutaneous melanoma patients: Are they useful for patients with a single positive sentinel node?

Background and ObjectivesOf clinically node‐negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non‐sentinel lymph nodes (NSLNs). Approximately 80% of SLN‐positive patients have a single positive SLN.MethodsTo assess whether state‐of‐the‐art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single‐institution cohort of 143 patients with cN0 SLN‐positive primary melanoma who underwent subsequent completion lymph node dissection. We used sensitivity (SE) and positive predictive value (PPV) to characterize the ability of the models to identify patients at high risk for NSLN disease.ResultsAcross Stage III patients, all clinicopathologic models tested had comparable performances. The best performing model identified 52% of NSLN‐positive patients (SE = 52%, PPV = 37%). However, for the single SLN‐positive subgroup (78% of cohort), none of the models identified high‐risk patients (SE > 20%, PPV > 20%) irrespective of the chosen probability threshold used to define the binary risk labels. Thus, we designed a new model to identify high‐risk patients with a single positive SLN, which achieved a sensitivity of 49% (PPV = 26%).ConclusionFor the largest SLN‐positive subgroup, those with a single positive SLN, current model performance is inadequate. New approaches are needed to better estimate nodal disease burden of these patients.

SKA3 overexpression predicts poor outcomes in skin cutaneous melanoma patients

BackgroundSpindle and Kinetochore Associated Complex Subunit 3 (SKA3) is a part of the SKA complex, which plays a key role in cell mitosis. Studies have shown that SKA3 was associated with cancer progression. However, its role in skin cutaneous melanoma (SKCM) remains unclear. Here, we investigated the expression level and prognostic value of SKA3 in SKCM. MethodsBased on public databases, univariate and multivariate Cox regression analyses were used to investigate the different expression of SKA3 between SKCM and normal tissues. Then, the relationship between SKA3 expression level and prognosis was assessed. PPI network and functional enrichment analysis were performed. ESTIMATE and CIBERSORT were expected to evaluate the SKA3 expression and immune status. CCK8, wound healing, transwell assays and tumor xenograft trial were performed to detect the SKA3 function in cell viability, migration and invasion of the cell lines. ResultsThe SKA3 was highly expressed in SKCM tissues. SKA3 overexpression was associated with poor survival and immune status. SKA3 knockdown inhibited cell viability, migration and invasion of SKCM cells. ConclusionSKA3 is involved in the progression of SKCM and may serve as a new prognostic biomarker and therapeutic target.

Prognostic Value of Interleukin-32 Expression and Its Correlation with the Infiltration of Natural Killer Cells in Cutaneous Melanoma.

Interleukin-32 (IL-32) is well known as a proinflammatory cytokine that is expressed in various immune cells and cancers. However, the clinical relevance of IL-32 expression in cutaneous melanoma has not been comprehensively studied. Here, we identified the prognostic value of IL32 expression using various systematic multiomic analyses. The IL32 expressions were significantly higher in cutaneous melanoma than in normal tissue, and Kaplan–Meier survival analysis showed a correlation between IL32 expression and good prognosis in cutaneous melanoma patients. In addition, we analyzed the correlation between IL32 expression and the infiltration of natural killer (NK) cells to identify a relevant mechanism between IL32 expression and prognosis in cutaneous melanoma (p = 0.00031). In the relationship between IL32 expression and the infiltration of NK cells, a negative correlation was found in resting NK cells (rho = −0.38, p = 3.95 × 10−17) whereas a strong positive correlation was observed only in active NK cells (rho = 0.374, p = 1.23 × 10−16). Moreover, IL32 expression was markedly positively correlated with the cytolytic molecules, such as granzyme and perforin. These data suggest that IL32 expression may increase patient survival through the infiltration and activation of NK cells, representative anticancer effector cells, in cutaneous melanoma. Collectively, this study provides the prognostic value of IL32 expression and its potential role as an effective predictive biomarker for NK cell infiltration in cutaneous melanoma.

1099 Financial Implications of Implementing MSLT-II Trial Findings for Treatment of Cutaneous Malignant Melanoma Patients in A Tertiary Referral Centre in The United Kingdom

Abstract Aim Cutaneous malignant melanoma is a significant public health challenge in the United Kingdom. Since the new American Joint Committee on Cancer (AJCC) version 8 definition of melanoma staging, more melanoma patients are eligible for sentinel lymph node biopsies (SLNB). Prior to the MSLT-II trial, SLNB positive patients were treated as a distinct group within cutaneous melanoma patients and in most centres would routinely undergo lymph node clearance (LNC) of the regional lymph node basin to control disease. Given the above developments in melanoma care, we compared the cost of SLNB and monitoring to the cost of LNC for patients with melanoma. Method We retrospectively reviewed all SLNB positive patients undergoing LNC or surveillance in 2019. We measured the cost of all clinical encounters for both groups and performed a cost analysis. Results Our study shows that the mean cost per patient of axillary LNC is £4731.64 and groin LNC is £5381.78 against a cost of £2896.67 for SLNBs. Mean inpatient stay was 2.8 nights following LNC and 0.11 nights following SLNB. 50% of LNCs and 11% of SLNBs were associated with post-operative complications. Conclusions Our data shows that treating uncomplicated SLNB positive patients with surveillance rather than immediate LNC results in reduced morbidity, lower complication rate and shorter inpatient stay for the patients, as well as lower financial burden to the unit. This is reflected by the UK Consensus statement on melanoma, suggesting that LNC should not be routinely offered for positive SLNB without high-risk features.

878 Optimizing Follow Up for Melanoma Patients: Are We Meeting NICE Guidance?

Abstract Introduction St. George’s University Hospitals NHS Foundation Trust is a designated tertiary referral Centre for all skin cancers serving a population of 3.5 million in and around South West London. It has an international reputation for its management of melanoma cases. All melanoma patients need frequent follow up visits for a long period of time which may extend to more than 10 years. Many aspects should be included when following up these patients including clinical assessment, laboratory, and radiological evaluation. Aim The aim of this project is to assess the quality of laboratory follow up of melanoma patients focusing on optimizing vitamin D level. Method We performed a retrospective review of cutaneous melanoma patients in 2019. Laboratory standards for follow up of vitamin D level was identified from NICE guidance 2015. After introduction of a condensed guide, a second review was performed in 2020. Results In the first cycle, 63 patients were included. Only 47% of them had their Vitamin D levels checked at time of diagnosis. Follow up check for vitamin D level was only done in 36%. Following introduction of guidance, 36 patients have been included. Significant improvement in both parameters with rate of 65% and 96% respectively. Conclusions Although we managed to improve our adherence to NICE guidance, more effort is still needed to improve all patients' care. We are willing to conduct a qualitative survey asking staff to explore their obstacles.

Using Immune-Related lncRNA Signature for Prognosis and Response to Immunotherapy in Cutaneous Melanoma.

BackgroundCutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment.MethodsWe downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high- and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy.ResultsBy correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan–Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature.ConclusionThe 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy.

The Utility of Indocyanine Green Dye Fluorescence Lymphography and Angiography During Wide Excision of Cutaneous Melanoma.

Background and Objectives. Lymph node status is the most important prognostic factor in cutaneous melanoma patients. Recent studies showed that indocyanine green (ICG) fluorescence lymphography helps locating sentinel nodes better. Sometimes, flap reconstruction is needed after wide excision of tumor. Indocyanine green fluorescence also simplifies the intraoperative design of flaps. This study investigates the use of ICG fluorescence in patients with cutaneous melanoma during operation. Methods. We performed a single-center, retrospective study of subjects with cutaneous melanoma using ICG lymphograhy and/or angiography during wide excision of tumor between 2015 and 2019. Patients received a dermal injection of ICG and patent blue (PB) dye. The positive node was excised. Indocyanine green angiography was utilized to visualize better skin paddle during flap reconstruction if needed. Results. A total of 37 sentinel lymph nodes (SLNs) were removed in 12 patients. Indocyanine green successful localization was found in 10 of the 12 patients (83%). Three patients were found with 6 metastatic nodes on final pathology. 100% of these 6 nodes were identified by ICG, while 83% (5/6) were positive PB. Three of the 12 patients received flap reconstruction after operation, and no major complications occurred. Conclusions. ICG dye lymphangiography is a good alternative for locating SLNs in patients with melanoma. It could also visualize well perfusion skin paddle during reconstruction. We reported a reproducible and simple method to utilize ICG fluorescence in cutaneous melanoma patients.