Site Of Melanoma Research Articles

The Prognostic Significance of Tumoral Melanosis.

Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent. We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS). TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS. TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Inducible CCR2+ nonclassical monocytes mediate the regression of cancer metastasis.

A major limitation of immunotherapy is the development of resistance resulting from cancer-mediated inhibition of host lymphocytes. Cancer cells release CCL2 to recruit classical monocytes expressing its receptor CCR2 for the promotion of metastasis and resistance to immunosurveillance. In the circulation, some CCR2-expressing classical monocytes lose CCR2 and differentiate into intravascular nonclassical monocytes that have anticancer properties but are unable to access extravascular tumor sites. We found that in mice and humans, an ontogenetically distinct subset of naturally underrepresented CCR2-expressing nonclassical monocytes was expanded during inflammatory states such as organ transplant and COVID-19 infection. These cells could be induced during health by treatment of classical monocytes with small-molecule activators of NOD2. The presence of CCR2 enabled these inducible nonclassical monocytes to infiltrate both intra- and extravascular metastatic sites of melanoma, lung, breast, and colon cancer in murine models, and they reversed the increased susceptibility of Nod2-/- mutant mice to cancer metastasis. Within the tumor colonies, CCR2+ nonclassical monocytes secreted CCL6 to recruit NK cells that mediated tumor regression, independent of T and B lymphocytes. Hence, pharmacological induction of CCR2+ nonclassical monocytes might be useful for immunotherapy-resistant cancers.

53342 Epidemiology and Primary Site of Melanoma in Asian Patients

53342 Epidemiology and Primary Site of Melanoma in Asian Patients

Patterns of forearm lymphatic drainage to the epitrochlear lymph nodes in 1400 cutaneous melanoma patients.

Variations of hand and forearm lymphatic drainage to upper-arm lymphatic pathways may impact the route of melanoma metastasis. This study compared rates of lymphatic drainage to epitrochlear nodes between anatomic divisions of the hand and forearm to determine whether the anatomic distribution of hand and forearm melanomas affects the likelihood of drainage to epitrochlear lymph nodes. Using a single-institution lymphoscintigraphy database, we identified all patients with cutaneous melanoma on the hand and forearm. A body-map two-dimensional coordinate system was used to classify cutaneous melanoma sites between radial-ulnar and dorsal-volar divisions. Sentinel lymph nodes (SLNs) visualized on lymphoscintigraphy were recorded. Proportions of patients with epitrochlear SLNs were compared between anatomic divisions using χ2 analysis. Of 3628 upper extremity cutaneous melanoma patients who underwent lymphatic mapping with lymphoscintigraphy, 1400 met inclusion criteria. Twenty-one percent of patients demonstrated epitrochlear SLNs. Epitrochlear SLNs were observed in 27% of dorsal forearm melanomas and 15% of volar forearm melanomas (p < 0.001). Epitrochlear SLNs were observed in 31% of ulnar forearm melanomas and 17% of radial forearm melanomas (p < 0.001). Higher proportions of dorsal and ulnar forearm melanomas have epitrochlear SLNs. Metastasis to epitrochlear SLNs may be more likely from melanomas in these respective forearm regions.

Primary Malignant Melanoma of the Hard Palate: A Rare Case Report

Background: Primary malignant melanoma of the oral cavity is an uncommon and aggressive malignancy with a poor prognosis. The hard palate is a rare site for primary melanoma, and early diagnosis is often challenging due to its asymptomatic nature in the initial stages. Case presentation: We present the case of a 58-year-old female who presented with a pigmented lesion on the right hard palate and a neck mass. The lesion had been present for a year and had gradually increased in size. The neck mass had appeared three months prior and was associated with pain. Imaging and biopsy confirmed the diagnosis of malignant melanoma with cervical lymph node metastasis. The patient underwent wide excision with right hemimaxillectomy and modified radical neck dissection type II, followed by planned postoperative radiation therapy. Conclusion: This case highlights the importance of considering melanoma in the differential diagnosis of pigmented oral lesions. Early diagnosis and aggressive treatment are crucial for improving outcomes in this rare but aggressive malignancy. The use of adjuvant therapies, such as radiation and targeted therapy, may be beneficial in select cases.

Efficacy of axitinib in a US cohort of patients with programmed cell death protein 1-resistant mucosal melanoma.

Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ± anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021. Radiologic response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Twenty-three patients were included in this study. In all, 78% were females with a median age of 62 years. The originating site of mucosal melanoma was the sinonasal (35%), genitourinary (35%), and gastrointestinal (30%) tracts. Sixty-five percent of patients had M1c or M1d disease and 0% had BRAF V600 mutations detected. The majority (96%) had prior treatment inclusive of anti-PD-1, with a median of 2 prior lines, and 78% of patients received a combination of axitinib and PD-1 and the median duration of treatment was 3.2 months. The overall response rate was 13% and the disease control rate was 26%. The median progression-free survival was 3.2 months, and the median overall survival was 8.2 months. Overall, the regimen was well tolerated with 39% of patients requiring dose reduction and 9% requiring treatment cessation. Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.

The MARIANE-trial: Multicenter phase 1b/2 trial testing safety and efficacy of neoadjuvant intradermal ipilimumab and nivolumab in high-risk stage II melanoma.

TPS9615 Background: Adjuvant anti-PD1 (nivolumab or pembrolizumab) has been shown to improve relapse free survival for patients with high-risk stage II melanoma (IIB-C). However, this therapy probably won’t be reimbursed as standard of care in most European countries due to high costs, and the benefit-risk-ratio. For macroscopic stage III melanoma, neoadjuvant ipilimumab (IPI; anti-CTLA4) plus nivolumab (NIVO; anti-PD1) has been shown to induce high pathologic response rates in the resected lymph nodes, long-term event free survival, and this schedule is currently being compared to adjuvant NIVO in a phase 3 study (NCT04949113). This combination schedule, however, is unsuitable for earlier disease stages, due to high costs and clinical toxicity. In preclinical models, a local tumor draining lymph node directed delivery of anti-PD-1 plus anti-CTLA-4 has been demonstrated to outperform systemic administration on induction of T-cell proliferation and tumor control. In patients, local delivery of anti-PD-1 or anti-CTLA-4 has been suggested to be equally effective in tumor control with a reduction of adverse events. These data have formed the rationale for testing intradermal injections at the excision site of the primary tumor with IPI and NIVO prior to the re-excision and sentinel node procedure in high-risk stage II melanoma patients. Methods: This multicenter, dose-escalating phase Ib/II trial, using a Simon’s two-stage design, is the first trial to test feasibility and efficacy of intradermal IPI plus NIVO in high-risk stage II melanoma patients. In total 21 to 80 patients, diagnosed with a stage T3-4 cutaneous melanoma with ≥ 50% chance of positive sentinel node, naïve for re-excision, sentinel node surgery and immunotherapy, will be included in this trial. Patients will receive 2 cycles of intradermal IPI 0.5 mg + NIVO 1 mg at the excision site of the primary melanoma (every 3 weeks; arm A); 6 cycles intradermal IPI 0.5 mg + NIVO 1 mg (every week; arm B); 2 cycles intradermal IPI 10 mg + NIVO 20 mg (every 3 weeks, arm C); or 2 cycles of intravenous nivolumab 240 mg every 3 weeks combined with the most optimal intradermal regimen of IPI + NIVO (based on the results of arm A, B or C) in arm D. In week 6, patients will undergo sentinel node surgery, whereafter only patients with a non-MPR (&gt;10% vital tumor) will be treated with adjuvant anti-PD1 according to current standard of care. We expect the first patient to be enrolled in March 2024and to be accruing for 1-1.5 years. Clinical trial information: NCT06240143 .

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

Ambient ultraviolet radiation and ocular melanoma incidence in the United States, 2000−2019

Background/ObjectivesOcular melanoma is a rare, but deadly cancer. This large cancer registry study examines the associations between solar ultraviolet radiation (UVR) and incidence of different anatomical sites of ocular melanoma by sex, age, laterality, and race and ethnicity.MethodsIncidence data were derived from 21 cancer registries in the US for the years 2000–2019. Satellite-based UVR estimates were linked to county of residence at diagnosis. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quartiles using Poisson models.ResultsUVR was not associated with total ocular melanoma (N = 18,089) comparing Q4 versus Q1 (IRR = 0.98; 95%CI:0.94,1.03; p-trend = 0.07) or conjunctival melanoma (IRR = 0.99; 95%CI:0.82,1.19; p-trend = 0.81). However, in analyses of continuous UVR (per 10 mW/m2), risks were reduced for total ocular melanoma (IRR = 0.97; 95% CI: 0.96, 0.99). Incidence was increased for ciliary body/iris melanoma in the highest UVR quartile (IRR = 1.63; 95%CI:1.43,1.87; p-trend < 0.0001) and remained increased in non-Hispanic White individuals only. Incidence was reduced for choroidal melanoma in the highest UVR quartile (IRR = 0.86; 95%CI:0.82,0.91; p-trend < 0.0001).ConclusionsUVR may be associated with increased risk of ciliary body/iris melanoma. Reduced risk of choroidal melanoma may be due to higher diffuse UVR exposure to posterior ocular sites in locations at higher latitudes. Our results support and expand previous findings of associations of UVR using various surrogates on ocular melanoma risk and serve as a starting point for understanding the differences in the relationship between UVR and specific anatomical sites.

High UV damage and low repair, but not cytosine deamination, stimulate mutation hotspots at ETS binding sites in melanoma

Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ultraviolet) damage sequencing data and analyzed cyclobutane pyrimidine dimer (CPD) formation, DNA repair, and CPD deamination in human cells at single-nucleotide resolution. Our data show prominent CPD hotspots immediately after UV irradiation at ETS binding sites, particularly at sites with a conserved TTCCGG motif, which correlate with mutation hotspots identified in cutaneous melanoma. Additionally, CPDs are repaired slower at ETS binding sites than in flanking DNA. Cytosine deamination in CPDs to uracil is suggested as an important step for UV mutagenesis. However, we found that CPD deamination is significantly suppressed at ETS binding sites, particularly for the CPD hotspot on the 5' side of the ETS motif, arguing against a role for CPD deamination in promoting ETS-associated UV mutations. Finally, we analyzed a subset of frequently mutated promoters, including the ribosomal protein genes RPL13A and RPS20, and found that mutations in the ETS motif can significantly reduce the promoter activity. Thus, our data identify high UV damage and low repair, but not CPD deamination, as the main mechanism for ETS-associated mutations in melanoma and uncover important roles of often-overlooked mutation hotspots in perturbing gene transcription.

Characteristics of adaptive immune effectors involved in the secondary xenogeneic immune response to human melanoma cells

Introduction. Current approaches are being developed for adoptive cancer therapy using T-cells genetically modified with T-cell receptors (TCRs) with specificity for tumor antigens. The complexities of identifying antigen-specific TCRs in a patient’s repertoire and selecting therapeutic receptors necessitate the development of experimental strategies for generating tumor-specific T cells. One of such approaches could be the xenogeneic immunization of mice with human tumor cells. It seems plausible that the T cell repertoire stimulated by xenogeneic vaccination could be a source of TCRs suitable for adoptive cancer immunotherapy.Aim. To assess the prospects for using xenogeneic immunizations to generate tumor-specific memory T cells and identify their TCRs suitable for adoptive immunotherapy, we studied the dynamics of the secondary xenogeneic response in a model of induction of an immune response in mice to human melanoma cells.Materials and methods. Mice were immunized with human melanoma cells, and 45 days later, they were re-challenged with the immunizing tumor. The dynamics of the development of the secondary immune response in vivo and the composition of the involved effectors of adaptive immunity were analyzed by flow cytometry. The proliferation of lymphocytes from immune mice in response to human melanoma cells was evaluated in in vitro culture.Results. The secondary xenogeneic response was characterized by a more intense accumulation of T cells and the rapid development of the effector phase at the injection site of human melanoma. This correlated with an enhanced in vitro proliferative response of lymphocytes from immune animals to xenoantigens of the immunizing tumor. CD4+ and CD8+ memory T cells contributed equally to the development of a secondary response to human melanoma cells expressing HLA class I and II molecules. When only HLA class I was expressed on the cells of the immunizing xenogeneic tumor, CD8+ memory cells were formed, which dominated the secondary immune response.Conclusion. Our findings confirmed the formation of a specific immunological memory for xenoantigens during xenogeneic immunization. This suggests the possibility of generating xenogeneic TCRs specific for human tumor antigens, which opens up opportunities to developing approaches for screening among them for receptor variants suited for adoptive immunotherapy of human cancers.

EPID-03. SEX DIFFERENCES IN ODDS OF BRAIN METASTASIS AND OUTCOMES BY BRAIN METASTASIS STATUS AFTER ADVANCED MELANOMA DIAGNOSIS

Abstract Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among individuals with advanced melanoma. Using the nationwide Flatiron Health electronic health record-derived deidentified database, we evaluated individuals diagnosed with advanced melanomafrom 1/1/11-07/30/22 who received oncologist-defined rule-based first line of therapy (N = 7,969, 33% female according to EHR, 35% w/ documentation of brain metastases). Odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (aOR: 1.22, 95% CI:1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI:1.04, 1.28) but not rwPFS (aHR: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among individuals with advanced melanoma not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

Correlations between inflammatory cytokine levels and degree of pigmentation in acral melanomas.

Cutaneous melanoma, a highly aggressive skin tumor, is characterized by complex signaling pathways in terms of its pathogenesis and progression. Although the degree of pigmentation in melanoma determines its progression, metastasis, and prognosis, its association with inflammatory cytokines remains unclear. Thus, we evaluated the associations between melanoma pigmentation and plasma levels of inflammatory cytokines; furthermore, we investigated the potential variations in this relationship across the primary anatomic sites of melanoma. We enrolled patients with cutaneous melanoma who visited Chonnam National University Hwasun Hospital between January 2021 and December 2021. The anatomical sites of melanoma were categorized as acral and non-acral sites. The degree of pigmentation was quantified using computer software. In total, nine inflammatory cytokines were analyzed, including interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). This study included 80 melanoma patients. Of these, 53 had acral melanoma and 27 had non-acral melanoma. Overall, plasma concentrations of IL-2, IL-4, IL-5, GM-CSF, and IFN-γ demonstrated significant correlations with diminished pigmentation. Furthermore, in the acral melanoma patients group, plasma concentrations of IL-2, IL-4, IL-5, GM-CSF, IFN-γ, and TNF-α revealed significant correlations with diminished pigmentation. Our results reveal significant associations between melanoma pigmentation and various cytokine levels, particularly in acral melanoma patients; these associations can be influenced by factors related to acral melanoma, such as physical stress or trauma. These correlations may also provide directions for the treatment of acral melanoma.

Characterization of hypermetabolic lymph nodes after SARS-CoV-2 vaccination using PET-CT derived node-RADS, in patients with melanoma

This study aimed to evaluate the diagnostic accuracy of Node Reporting and Data System (Node-RADS) in discriminating between normal, reactive, and metastatic axillary LNs in patients with melanoma who underwent SARS-CoV-2 vaccination. Patients with proven melanoma who underwent a 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) between February and April 2021 were included in this retrospective study. Primary melanoma site, vaccination status, injection site, and 2-[18F]-FDG PET/CT were used to classify axillary LNs into normal, inflammatory, and metastatic (combined classification). An adapted Node-RADS classification (A-Node-RADS) was generated based on LN anatomical characteristics on low-dose CT images and compared to the combined classification. 108 patients were included in the study (54 vaccinated). HALNs were detected in 42 patients (32.8%), of whom 97.6% were vaccinated. 172 LNs were classified as normal, 30 as inflammatory, and 14 as metastatic using the combined classification. 152, 22, 29, 12, and 1 LNs were classified A-Node-RADS 1, 2, 3, 4, and 5, respectively. Hence, 174, 29, and 13 LNs were deemed benign, equivocal, and metastatic. The concordance between the classifications was very good (Cohen’s k: 0.91, CI 0.86–0.95; p-value < 0.0001). A-Node-RADS can assist the classification of axillary LNs in melanoma patients who underwent 2-[18F]-FDG PET/CT and SARS-CoV-2 vaccination.

Subcutaneous Rapid Dissolution Microneedle Patch Integrated with CuO2 and Disulfiram for Augmented Antimelanoma Efficacy through Multimodal Synergy of Photothermal Therapy, Chemodynamic Therapy, and Chemotherapy.

Melanoma is a malignancy of the skin that is resistant to conventional treatment, necessitating the development of effective and safe new therapies. The percutaneous microneedle (MN) system has garnered increasing interest as a viable treatment option due to its high efficacy, minimal invasiveness, painlessness, and secure benefits. In this investigation, a sensitive MN system with multiple functions was created to combat melanoma effectively. This MN system utilized polyvinylpyrrolidone (PVP) as microneedle substrates and biocompatibility panax notoginseng polysaccharide (PNPS) as microneedle tips, which encapsulated PVP-stabilized CuO2 nanoparticles as a therapeutic agent and disulfiram-containing F127 micelles to enhance the tumor treatment effect. The MN system had sufficient mechanical properties to pierce the skin, and the excellent water solubility of PNPS brought high-speed dissolution properties under the bio conditions, allowing the MNs to effectively penetrate the skin and deliver the CuO2 nanoparticles as well as the drug-loaded micelles to the melanoma site. CuO2 nanoparticles released by the MN system generated Cu2+ and H2O2 in the tumor acidic environment to achieve self-supply of hydrogen peroxide to chemodynamic therapy (CDT). In addition, Cu2+ was chelated with disulfiram to produce CuET, which killed tumor cells. And the MN system had excellent near-infrared (NIR) photothermal properties due to the loading of CuO2 nanoparticles and induced localized thermotherapy in the melanoma region to further inhibit tumor growth. Thus, the designed MN system accomplished effective tumor suppression and minimal side effects in vivo via combined therapy, offering patients a safe and effective option for melanoma treatment.

Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase).

The tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment. Patients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS). 973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients' characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively). Our study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research.

40727 Associations Between Primary Cutaneous Melanoma Site and Metastatic Disease Site

40727 Associations Between Primary Cutaneous Melanoma Site and Metastatic Disease Site

Cutaneous Malignant Melanoma with Testicular Metastases in a Wild Rabbit (Oryctolagus cuniculus).

Melanocytic skin tumours have been rarely described in pet rabbits, and exposure to UV light in sparsely haired areas has been hypothesised to play a cancerogenic role. Here, we describe a case of cutaneous malignant melanoma arising from the skin of the scrotum in an 8-year-old male wild rabbit, with testicular metastases as an unusual metastatic site for melanoma reported in humans to date. The tumour was nearly 5 cm in size, firm, and highly pigmented, with multifocal superficial ulcerations and large areas of intratumoural necrosis. The adjacent testis was 1.5 cm, multinodular, and black, obscuring tissue morphology. Histologically, the dermis was expanded by an infiltrative, densely cellular neoplasm composed of nests and sheets of polygonal to spindle neoplastic melanocytes, supported by scant fibrovascular stroma. Neoplastic cells showed intermediate N/C ratio, moderate basophilic cytoplasm, often obscured by abundant brownish granular pigment, and eccentric nuclei with prominent nucleoli. Cellular pleomorphism and nuclear atypia were severe, and high mitotic activity was observed. Diffuse dermal lymphovascular invasion was also observed. The testis was delimited by a thin tunica albuginea, and the parenchyma was largely obscured in its morphology by densely packed neoplastic cells. Seminiferous tubules, lined with a thin basement membrane and containing neoplastic and scattered spermatogenic cells, were occasionally observed. Neoplastic cells within the skin and the testis were positive for HMB-45, Melan-A, and S-100. The growing popularity of rabbits as pets allows for a greater ability to accumulate data on the spontaneous occurrence of tumours in these animals. Furthermore, descriptions of the biological aspects of spontaneously occurring tumours may serve to improve current knowledge in animal species and humans in which the same neoplasm may occur.

P50 Exploring unmet needs and attitudes to skin self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Melanoma specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale, and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n &amp;lt; 5; &amp;lt; 2.5%). SSE barrier and benefit scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) were identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)] and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.

DS09 (P50) Exploring Unmet Needs and Attitudes to Skin ­Self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory—Short Form (FCRI-SF), Melanoma-specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n &amp;lt; 5; &amp;lt; 2.5%). Skin self-examination barriers and benefits scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)], and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.