Localized Melanoma Research Articles

Participant Motivators and Expectations in the MEL-SELF Randomized Clinical Trial of Patient-Led Surveillance for Recurrent Melanoma: Content Analysis of Survey Responses.

Limited data exist on the motivations and expectations of participants when enrolling in dermatology clinical trials, including melanoma early detection trials. Understanding participant motivators for research engagement has been identified as a prioritized area for trial methodology research. The study aimed to determine motivators of participation and expectations from trial involvement among patients enrolled in the MEL-SELF randomized clinical trial of patient-led surveillance for new or recurrent melanoma. The MEL-SELF trial is recruiting patients previously treated for localized melanoma, who own a smartphone, have a partner to assist with skin self-examination (SSE), and attend routinely scheduled follow-up at specialist and primary care skin clinics in Australia. We evaluated responses from the first 100 randomized participants to 2 open-ended questions about their motivations and expectations for participating in the trial, administered through the internet-based baseline questionnaire. A total of 3 coders independently coded the free-text responses and resolved discrepancies through consensus. Qualitative content analysis by an iterative process was used to group responses into themes. Responses from potential participants who were not randomized and the 404 participants randomized subsequently into the trial, were also checked for new themes. Coding and analysis were conducted in Microsoft Excel. Out of the 100 survey participants, 98 (98%) answered at least 1 of the 2 questions. Overall, responses across the motivation and expectation items indicated 3 broad themes: community benefit, perceived personal benefit, and trusting relationship with their health care provider. The most common motivators for participation were related to community benefit. These included progressing medical research, benefitting future melanoma patients who may have similar experiences, and broader altruistic sentiments such as "helping others" or "giving back." The most common expectations from the trial related to personal benefit. These included perceived improved outcomes such as earlier diagnosis and treatment, access to additional care, and increased self-empowerment to take actions themselves that benefit their health. Patients expressed a desire to gain health-related knowledge and skills and were interested in the potential advantages of teledermatology. There were no new themes in responses from those who were not randomized or were randomized subsequent to the first 100. We report a tailorable, patient-focused approach to identify drivers of research engagement in clinical research. Clinical trials offer an opportunity to collate a substantial evidence base on determinants of research participation and to identify context-specific factors. Results from the MEL-SELF trial emphasized notable altruism, self-empowerment, and perceived advantages of teledermatology as specific motivators. These findings informed consent processes, recruitment, retention, response to trial tasks, and intervention adherence for the MEL-SELF host trial. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379527.

Trends in Melanoma Incidence, Prevalence, Stage at Diagnosis, and Survival: An Analysis of the United States Cancer Statistics (USCS) Database.

Background and objectives Melanoma, a major skin cancer, has seen varying trends in incidence, prevalence, stage atdiagnosis, and survival. This study examines these trends using the United States CancerStatistics (USCS) database, covering the period from 1999 to 2021. Methods We extracted data from the USCS database, which integrates the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program and the Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR). The analysis included new melanoma cases, prevalence estimates (using a 20-year limited duration), stage at diagnosis, and five-year relative survival rates. Incidence rates were adjusted for age using the 2000 United States standard population. Descriptive and trend analyses were performed using IBM SPSS Statistics software, version 29 (IBM Corp., Armonk, NY). Results The analysis of melanoma trends from 1999 to 2021 reveals a significant increase in the annual age-adjusted incidence rate, rising from 15.1 per 100,000 (95% CI: 14.9- 15.2) in 1999 to 23.0 per 100,000 (95% CI: 22.8- 23.1) in 2021. This upward trend is consistent across gender and racial/ethnic groups. The prevalence of melanoma over a 20-year period was 0.279 (95% CI: 0.276-0.282), with males showing a higher prevalence (0.302, 95% CI: 0.298-0.306) compared to females (0.256, 95% CI: 0.252-0.260). The distribution of melanoma stage at diagnosis indicated that 77% of cases were localized (95% CI: 76.5-77.5%), 9.5% regional (95% CI: 9.2-9.8%), 4.7% distant (95% CI: 4.4-5.0%), and 8.8% unstaged (95% CI: 8.5-9.1%). Survival analysis showed a five-year relative survival rate of 99.4% (95% CI: 99.2-99.6%) for localized melanoma and 35.6% (95% CI: 33.7-37.6%) for distant melanoma, highlighting significant disparities in survival based on stage at diagnosis. Conclusions The study highlights a rising incidence of melanoma and emphasizes the critical role of early detection in improving survival outcomes. The findings underscore the effectiveness of early diagnosis and the necessity for ongoing efforts to improve melanoma outcomes across diverse populations.

“There is a life before and after cancer”: experiences of resuming life and unmet care needs in stage I and II melanoma survivors

Although the largest increase in melanoma incidence is observed for localised melanoma, little research has been done on its impact. Despite favourable prognoses and relatively short treatment trajectories, diagnosis and treatment may significantly impact life post-treatment. Therefore, the aim of this study was to gain an in-depth understanding of stage I and II melanoma survivors’ experiences resuming life after treatment and their associated survivorship care (SSC) needs. A qualitative focus group study was conducted with 18 stage I or II melanoma survivors, divided over three focus groups with 6 survivors each. Transcripts were analysed through thorough thematic content analysis, using multiple phases of coding. In resuming life, survivors experienced profound initial impacts of disease and treatment, fed by a perceived lack of knowledge and underestimation of melanoma. They faced unexpected physical and emotional effects post-surgery, experiencing mixed feelings from relief to fear and uncertainty. Survivors felt misunderstood, had to adjust their lives, and managed personal and external expectations while experiencing a positive shift in life perspective, leading to a notable difference in life before and after cancer. In terms of SSC needs, survivors stressed the need for tailored information, accessible resources, patient-centered follow-up, and supportive care addressing the total impact of disease and treatment. These findings highlight the importance of improving melanoma awareness and providing holistic SSC not only to advanced, but also to localised melanoma survivors. A tailored survivorship care plan could facilitate access to information and supportive care, helping patients resume their lives.

DNA methylation variations of DNA damage response correlate survival and local immune status in melanomas.

We aimed to explore the impact of DNA methylation alterations on the DNA damage response (DDR) in melanoma prognosis and immunity. MATERIAL &METHODS: Different melanoma cohorts with molecular and clinical data were included. Hierarchical clustering utilizing different combinations of DDR-relevant CpGs yielded distinct melanoma subtypes, which were characteristic of different prognoses, transcriptional function profiles of DDR, and immunity and immunotherapy responsesbut were associated with similar tumor mutation burdens. We then constructed and validated a clinically applicable 4-CpG risk-score signature for predicting survival and immunotherapy response. Our study describes the close interrelationship amongDNA methylation, DDR machinery, local tumor immune status, melanoma prognosis, and immunotherapy response.

Melanoma Deaths by Thickness: Most Melanoma Deaths Are Not Attributable to Thin Melanomas

IntroductionPrevious population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States. MethodsA review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death. ResultsMost melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%). ConclusionsThe public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas.

The 31-GEP to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system.

9530 Background: Cutaneous melanoma (CM) metastasis to the central nervous system (CNS) has a poor prognosis; however, treatment of CNS metastasis while asymptomatic is associated with better outcomes. CNS imaging is not routinely recommended for patients with early-stage CM (i.e., AJCC stage I–II), yet ˜14% of patients with stage II melanoma will develop CNS metastases. The 31-gene expression profile test (31-GEP) identifies patients at a low (Class 1A), intermediate (Class 1B/2A), or high risk (Class 2B) of tumor recurrence and metastasis. We evaluated the association of CNS metastasis with the 31-GEP test result for the purpose of directing CNS-directed imaging to detect metastasis earlier and, thus, improve outcomes. Methods: A retrospective analysis of patients clinically tested with the 31-GEP from 2013-2017. Patients were included in the study if they had clinical or pathological AJCC stage I-II CM (n=1,662). Kaplan-Meier analysis was used to estimate 5-year recurrence-free survival (RFS), and the log-rank test was used to compare survival between groups. Patients with non-CNS metastasis were censored at the time of recurrence. Univariate analysis to identify predictors of CNS metastasis was performed for tumor location, mitotic rate, Breslow thickness, ulceration status, tumor-infiltrating lymphocytes, age, sex, regression, lymphovascular invasion, tumor subtype, and 31-GEP results. Only significant (p&lt;0.01) factors in univariate analysis were included in Cox multivariable analysis. Results: Median follow-up time was 4.6 years (range: 0.02-14.5 years). Patients with a CNS metastasis tended to have thicker tumors (median 1.1 vs. 0.8, p=0.003), higher mitotic rate/mm2 (median 2.5 vs. 1.0, p&lt;0.001) and a higher proportion of males (73% vs. 55%, p=0.03) than patients that did not develop CNS metastasis. Patients with a Class 2B result were significantly more likely to develop CNS metastasis (7.4% [15/202]) relative to patients with a Class 1B/2A (1.7% [5/291]) or Class 1A (0.9% [10/1,169], p&lt;0.001) 31-GEP result. Patients with a Class 2B result had significantly lower 5-year RFS than patients with a Class 1B/2A or Class 1A result (91.6% vs. 98.2% vs. 99.1%, p&lt;0.001) and had shorter times to CNS metastases (1.5 yrs. vs. 4.2 yrs. vs. 3.4 yrs. p&lt;0.001). In multivariable analysis, only the 31-GEP Class 2B (HR=9.42, p&lt;0.001) result was a significant predictor of CNS metastasis; mitotic rate, Breslow thickness, and ulceration were not significantly predictive. Conclusions: Under multivariable analysis, the 31-GEP was the only significant predictor of CNS metastasis, and CNS metastasis occurred early (1.5 yrs). Patients with early-stage I-II CM and a Class 2B result should be considered for CNS imaging to enable asymptomatic detection of CNS metastasis and, thus, improve survival relative to symptomatic CNS metastasis.

Abstract 3791: A prognostic signature based on inherited genetic polymorphisms for patients with uveal melanoma

Abstract Introduction: Uveal melanoma (UM) is the most frequent eye malignancy in adults. Two UM subtypes exist, defined by Gene Expression Profiling or by genomic status: GEP class 1/disomy 3 [D3] and GEP class 2/monosomy 3 [M3] defining low-risk or high-risk of developing metastasis, respectively. However, these prognostic signatures require tumor samples, which may be difficult to obtain. We previously identified by a genome-wide association study (GWAS) frequent single nucleotide polymorphisms (SNP) in IRF4 and HERC2 associated with risk for D3 or M3 UM, respectively (1). Here, we aim to design a prognostic signature for the D3 and M3 UM subtypes based on these constitutive polymorphisms, available from blood samples. Experimental Procedures: We used the GWAS cohort of 1476 UM patients genotyped on GSA or Omni5. Risk SNPs coupled with clinical variables were used on a cohort of 497 UM patients (191 D3, 306 M3) in a statistical machine learning process to define a predictive signature of UM subtype. A cohort of 852 UM patients was used for validation. Results: We retained two SNPs, rs12203592 (in IRF4) and rs12913832 (in HERC2), tumor diameter and thickness, age at diagnosis and gender. We validated the predictive model in the validation cohort. The predicted high-risk group showed a decrease in time to relapse (TR) (HR: 3.72 [2.57 - 5.41], logrank p-value = 1.35E-15), overall survival (OS) (HR: 3.85 [2.58 - 5.73], logrank p-value = 1.24E-14) and progression-free-survival (PFS) (HR: 3.61 [2.32 - 5.61], logrank p-value = 6.55E-11), compared with the predicted low-risk group. Conclusion: Common germline polymorphisms contribute to the prediction of metastatic risk in patients with localized uveal melanoma. This information could be especially useful when access to the tumor is problematic. 1. Mobuchon et al, J Natl Cancer Inst, 114, 2, (2022) Citation Format: Thibault Verrier, Anaïs Le Ven, Alexandre Houy, Agathe Garcia, Pierron Gaelle, Nathalie Cassoux, Manuel Rodrigues, Josselin Noirel, Marc-Henri Stern. A prognostic signature based on inherited genetic polymorphisms for patients with uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3791.

Exploring Mechanisms and Promising Treatments of Malignant Melanoma

Malignant melanoma is one of the 4 main types of skin cancer, among basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, and it is the most aggressive and metastatic form. Unfortunately, advanced-stage, metastatic patients have a 5-year survival rate of a mere 5% to 19%. The traditional first-line treatment option for localized cutaneous melanomas is a tumor and margin excision surgery; however, in advanced-stage patients, chemotherapy drugs and targeted therapies have emerged as a more effective treatment option. The rising incidence of malignant melanoma in the fair-skinned populations of North America, Europe, and Australia, along with rising resistance to immune checkpoint inhibitors (ICIs), underscores the importance of new, efficacious melanoma treatments. The novel and breakthrough development of two types of immunotherapies, T-cell receptor (TCR) engineered T-cell immunotherapy (TCR-T) and mRNA vaccines, are promising treatment options, especially for advanced-stage, metastatic patients. While these treatments are in the early stages of development, various clinical trials have resulted in positive outcomes. Lastly, this review will highlight the challenges and setbacks to immunotherapy and future directions. Immunotherapy may become the standard for melanoma treatment, however, by overcoming current barriers, only time will tell.

Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial

Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions.

Lived Experiences and Fear of Cancer Recurrence Among Survivors of Localized Cutaneous Melanoma

Most of the rapid increase in cutaneous melanoma incidence in the US has been localized disease that is treated surgically and is associated with high survival rates. However, little is known about the psychological well-being of survivors in the US. To explore the lived experiences and fear of cancer recurrence among survivors of localized cutaneous melanoma. This was a qualitative and survey-based study that used semistructured interviews and the Fear of Cancer Recurrence Inventory short form (FCRI-SF) survey tool with participants recruited from an academic dermatology practice affiliated with the University of Texas, Austin. Interviews were completed via telephone or in person from August 2021 to September 2022. Each of the 9 items in the FCRI-SF was rated on a 5-point Likert scale, scored from 0 to 4, with a maximum possible score of 36 points. Data analyses were performed from February 2022 to June 2023. Semistructured interviews were analyzed for themes and subthemes associated with the lived experiences of survivors of cutaneous melanoma. The FCRI-SF scores were tabulated, with scores of 13 or greater identifying potential cases of clinically significant fear of cancer recurrence. In all, 51 participants (mean [SD] age, 49.5 [11.7] years; 34 [67%] female and 17 [33%] male) with a history of localized melanoma (stage 0-IIA) completed the interview and survey. Among them, 17 (33%) had survived a diagnosis of stage 0 melanoma, and the remainder, at least 1 invasive melanoma diagnosis (stage I-IIA). Semistructured interviews revealed several themes: (1) emotions surrounding follow-up appointments, (2) intensity of melanoma surveillance, (3) lifestyle changes regarding sun exposure, and (4) thoughts about life and death. Thirty-eight of 51 participants had an FCRI-SF score above the threshold for clinical fear of cancer recurrence. This qualitative and survey-based study found that despite having an excellent prognosis, some survivors of localized melanoma, even those who had stage 0, have high rates of fear of cancer recurrence and intense survivorship experiences that affect their psychological well-being.

Epigenetic markers of choroidal melanoma

This study analyzed the expression pattern of miRNA-223 and miRNA-126 in patients with localized choroidal melanoma (CM) taking into account biometric parameters in the absence of metastases. Blood plasma of 84 patients with M0N0 CM aged 35-86 years (mean age 63.4±1.2 years) was investigated. The basis for the diagnosis of CM was the results of ophthalmological examination, optical coherence tomography, and ultrasound scanning. In all cases, the absence of metastases was proven (using computed tomography or magnetic resonance imaging). Control - plasma of 28 volunteers (mean age 62.9±1.42 years, age range 45-78 years), who did not have tumoral, autoimmune, or chronic inflammatory processes. The expression levels of miRNAs circulating in blood plasma were determined by real-time polymerase chain reaction. An increase in the expression levels of miRNA-223 and miRNA-126 in the plasma of all 84 patients with CM was confirmed compared to the control group. Features of the miRNA expression pattern that emerged with changes in the tumor's quantitative parameters were identified. Evaluation of the levels of miRNA-223 and miRNA-126 in the blood plasma of patients with CM can be used in clinical practice to clarify the diagnosis of CM, as well as to predict the development of hematogenous metastases.

Prognostic and predictive biomarkers in melanoma

Biomarkers help to inform the clinical management of patients with melanoma. For patients with clinically localised primary melanoma, biomarkers can help to predict post-surgical outcome (including via the use of risk prediction tools), better select patients for sentinel lymph node biopsy, and tailor catch-all follow-up protocols to the individual. Systemic drug treatments, including immune checkpoint inhibitor (ICI) therapies and BRAF-targeted therapies, have radically improved the prognosis of metastatic (stage III and IV) cutaneous melanoma patients, and also shown benefit in the earlier setting of stage IIB/C primary melanoma. Unfortunately, a response is far from guaranteed. Here, we review clinically relevant, established, and emerging, prognostic, and predictive pathological biomarkers that refine clinical decision-making in primary and metastatic melanoma patients. Gene expression profile assays and nomograms are emerging tools for prognostication and sentinel lymph node risk prediction in primary melanoma patients. Biomarkers incorporated into clinical practice guidelines include BRAF V600 mutations for the use of targeted therapies in metastatic cutaneous melanoma, and the HLA-A∗02:01 allele for the use of a bispecific fusion protein in metastatic uveal melanoma. Several predictive biomarkers have been proposed for ICI therapies but have not been incorporated into Australian clinical practice guidelines. Further research, validation, and assessment of clinical utility is required before more prognostic and predictive biomarkers are fluidly integrated into routine care.

Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma

The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. To develop time-to-event risk prediction models for melanoma metastatic recurrence. Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P<.001) and to locoregional recurrences only (HR: 5.79, P<.001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. Retrospective nature and cohort from one geography. These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.

Trends in the Utilization and Outcomes of Brachytherapy vs. Proton Therapy in Localized Uveal Melanoma in the United States

To determine the trends in the utilization of different techniques of radiation treatment in localized uveal melanoma in the United States and to determine the difference in outcome between brachytherapy (BT) and proton-beam therapy (PT). Using the North American Association of Central Cancer Registries (NAACCR), we identified 17451 patients with localized uveal melanoma with known both surgical and method of radiation therapy between 1995-2018. Univariate and multivariable analyses were performed to identify factors and characteristics that may have a potential impact on the treatment. Net survival was calculated using Relative survival in Ederer II cumulative expected method with actuarial. Overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier method and life-tables. The registries included 28.312 patients with uveal melanoma, out of them 22,983 patients with localized disease. Patients with known both surgical and method of radiation therapy were 17451 patients. We have studied this group further. The median age of this group was 61 (IQR 51-71), males were 51.9% (N = 9063), whites were 98.1% (N = 16921), and choroidal tumors were 87.8% (N = 15330). The median tumor thickness was 3.9mm (IQR 24-70), while, the median maximum tumor diameter was 11.3mm (IQR 8.0-14.4). The median follow-up time was 5.9 years (IQR 3.1-10.3). Among all patients, 57.5% (n = 10032) received BT, and 9.8% (n = 1708) received PT. Collectively, 30.1% (n = 5247) of the patients received no radiation treatment. BT constituted 14% of treatment modalities in 1995 and steadily increased to 65% in 2017. PT utilization was minimal in 1995 (1.4%) and also increased to 14.3% in 2017. Younger age and thinner tumor thickness were independently associated with better Cancer-specific survival (CSS) and overall survival (OS). For all patients who were treated primarily with radiation treatment, the 5-year OS was 85,9% and the 10-year OS was 77.2%. There were no differences in rates of OS or CSS between patients who were treated with BT or PT. There is a continuous increase in the utilization of both BT and PT in the treatment of localized uveal melanoma. Similar survival outcomes could be anticipated for both radiation treatment techniques.

Biopsy of the sentinel lymph nodes using indocyanine green fluorescence method in local cutaneous melanoma

Timely diagnosis and treatment of cutaneous melanoma are important problems as mortality for this pathology exceeds 70 % of all skin tumors, and in Russia this disease is diagnosed at stage I only in 35.7 % of cases. Correctly selected therapy offers good results, but effective treatment requires accurate staging involving detection of metastases in the sentinel lymph nodes which cannot be identified clinically. This review analyzes study data showing the effectiveness of detection of the sentinel lymph nodes using indocyanine green fluorescence method.

802 Are Patients with Malignant Melanoma Operated on Within National Cancer Waiting Time Standards?

Abstract Aim This audit evaluated the performance of the local melanoma referral pathway against national cancer wait times, to identify limiting factors and find solutions to deliver service in a safe and streamlined manner. Method Patients with malignant melanoma referred to general surgeons between March and June 2022 were identified retrospectively. Patients with other skin cancers, concurrent malignancy, metastatic melanoma, or those declining surgery were excluded. The date of each step of the referral pathway was noted for each patient using Microsoft Excel, and the difference between the dates was calculated. The percentage of compliance with the 31-day and 62-day wait was compared against the national operational standard. Results During the audit period, 59 patients with malignant melanoma were referred to the general surgeons, 22 of these were excluded for the aforementioned reasons. Of the remaining 37 patients, 65% were male and the average age was 66 years old. 83% of patients received their first treatment from diagnosis within 31 days, falling short of the 96% target. Only 60% of patients received surgery within the following 31 days. On average it took 56.8 days from diagnosis to surgical treatment, with wait time to operation varying from 15 days to 101 days. Conclusions Overall, the average time to surgery for patients with malignant melanoma was less than the target 62 days, however there was notable variation in the number of days patients waited for their operation. Further detailed analysis of cases with long wait times is required to reduce the risk of delaying vital cancer treatment.

Population-based prognostic instrument (SweMR 2.0) for melanoma-specific survival - An ideal tool for individualised treatment decisions for Swedish patients

IntroductionThe prognosis for patients with melanoma has improved due to better treatments in recent years and updated tools to accurately predict an individual's risk are warranted. This study aims to describe a prognostic instrument for patients with cutaneous melanoma and its potential as a clinical device for treatment decisions. MethodsPatients with localised invasive cutaneous melanoma diagnosed in 1990–2021 with data on tumour thickness were identified from the population-based Swedish Melanoma Registry. The parametric Royston-Parmar (RP) method was used to estimate melanoma-specific survival (MSS) probabilities. Separate models were constructed for patients (≤1 mm) and (>1 mm) and prognostic groups were created based on all combinations of age, sex, tumour site, tumour thickness, absence/presence of ulceration, histopathologic type, Clark's level of invasion, mitoses and sentinel lymph node (SLN) status. ResultsIn total, 72 616 patients were identified, 41 764 with melanoma ≤1 mm and 30 852 with melanoma >1 mm. The most important variable was tumour thickness for both (≤1 mm) and (>1 mm), that explained more than 50% of the survival. The second most important variables were mitoses (≤1 mm) and SLN status (>1 mm). The prognostic instrument successfully created probabilities for >30 000 prognostic groups. ConclusionsThe Swedish updated population-based prognostic instrument, predicts MSS survival up to 10 years after diagnosis. The prognostic instrument gives more representative and up-to-date prognostic information for Swedish patients with primary melanoma than the present AJCC staging. Additional to clinical use and the adjuvant setting, the information retrieved could be used to plan future studies.

Acceptability of a Hypothetical Reduction in Routinely Scheduled Clinic Visits Among Patients With History of a Localized Melanoma (MEL-SELF): Pilot Randomized Clinical Trial.

After treatment for a localized melanoma, patients attend routinely scheduled clinics to monitor for new primary or recurrent melanoma. Patient-led surveillance (skin self-examination with patient-performed teledermoscopy) is an alternative model of follow-up that could replace some routinely scheduled visits. This study aims to assess the acceptability of a hypothetical reduction in routinely scheduled visits among participants of the Melanoma Self Surveillance (MEL-SELF) pilot randomized clinical trial of patient-led surveillance (intervention) versus usual care (control). Patients previously treated for localized melanoma in New South Wales who were participating in the MEL-SELF pilot randomized clinical trial were asked to respond to a web-based questionnaire at baseline and after 6 months on trial. We used mixed methods to analyze the data. The main outcome of interest was the acceptability of a hypothetical reduction in routinely scheduled visits for melanoma surveillance. Of 100 randomized participants, 87 answered the questionnaire at baseline, 66 answered the questionnaire at 6 months, and 79 provided a free-text explanation at either time point. At 6 months, 33% (17/51) of the control group and 35% (17/49) of the intervention group indicated that a hypothetical reduction in routinely scheduled visits with all melanoma doctors was at least slightly acceptable (difference in proportions -1%, 95% CI -20% to 17%; P=.89). Participants suggested that prerequisites for a reduction in routinely scheduled visits would include that sufficient time had elapsed since the previous diagnosis without a new primary melanoma or recurrence, an unscheduled appointment could be made at short notice if the patient noticed something concerning, their melanoma doctor had suggested reducing their clinic visit frequency, and patients had confidence that patient-led surveillance was a safe and effective alternative. Participants suggested that a reduction in routinely scheduled visits would not be acceptable where they perceived a very high risk of new or recurrent melanoma, low self-efficacy in skin self-examination and in the use of technologies for the patient-led surveillance intervention, and where they had a preference for clinician-led surveillance. Some patients said that a partial reduction to once a year may be acceptable. Some patients may be receptive to a reduction in routinely scheduled visits if they are assured that patient-led surveillance is safe and effective. Australian New Zealand Clinical Trials Registry ACTRN12616001716459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865&isReview=true; ClinicalTrials.gov NCT03581188; https://clinicaltrials.gov/ct2/show/NCT03581188. RR2-10.1001/jamadermatol.2021.4704.

Causes of death among patients with cutaneous melanoma: a US population-based study

Research on mortality outcomes and non-cancer-related causes of death in patients with cutaneous melanoma (CM) remains limited. This study aimed to identify the prevalence of non-cancer-related deaths following CM diagnosis. The data of 224,624 patients diagnosed with malignant CM in the United States between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We stratified our cohort based on their melanoma stage at diagnosis and further calculated standardized mortality ratios (SMRs) for each cause of death, comparing their relative risk to that of the general US population. The total number of fatalities among melanoma patients was 60,110, representing 26.8% of the total cases. The percentage of deaths is directly proportional to the disease stage, reaching 80% in distant melanoma. The highest fatalities among the localized melanoma group (25,332; 60.5%) occurred from non-cancer causes, followed by melanoma-attributable deaths (10,817; 25.8%). Conversely, melanoma is the leading cause of death in regional and distant melanoma cohorts. Cardiovascular and cerebrovascular diseases were the most prevalent non-cancer causes of death among the three disease-stage cohorts. Compared to the general population, we did not observe an increased risk of death due to non-cancer causes in the localized CM cohort, while patients diagnosed with regional and distant CMs had a statistically significant higher risk of death from all the reported major causes of death.

Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial.

LBA9503 Background: mRNA-4157 is a novel mRNA-based personalized cancer vaccine which encodes up to 34 patient-specific tumor neoantigens. The open-label randomized Phase 2 mRNA-4157-P201/Keynote-942 trial met its primary endpoint of recurrence free survival (RFS) in patients with resected high-risk stage IIIB/C/D and IV melanoma. The study has shown a statistically significant and clinically meaningful improvement in RFS in the combination therapy compared to pembrolizumab monotherapy, with a reduction in the risk of recurrence or death by 44% (HR = 0.561; 95% CI: (0.309, 1.017); 1-sided p-value of 0.0266). This report provides the first analysis of the secondary efficacy endpoint of distant metastasis-free survival (DMFS). Methods: mRNA-4157-p201 is an ongoing multicenter, open-label, randomized Phase II trial in patients with completely resected, high-risk Stage IIIB/C/D and IV cutaneous melanoma. Patients were randomized 2:1 (stratified by stage) to receive mRNA-4157 in combination with pembrolizumab or pembrolizumab alone. mRNA-4157 (1mg) was administered intramuscularly every 3 weeks for a total of 9 doses and pembrolizumab (200mg) intravenously was given every 3 weeks for up to 18cycles. The primary endpoint was investigator-assessed RFS, defined as local, locoregional, distant recurrence, or new primary melanoma. The secondary endpoint of DMFS was pre-specified and hierarchically tested following positive RFS. All tests were performed at 1-sided alpha = 0.99. Results: 157 patients were randomized to the combination of mRNA-4157 with pembrolizumab (n = 107) or pembrolizumab monotherapy (n = 50). The primary analysis for the primary endpoint occurred after all patients completed a minimum of 12 months on study and 44 RFS events were observed. At a median follow-up of 23 (combination) and 24 (pembrolizumab) months in the primary analysis, RFS events were reported in 22.4% (24/107) of patients in the combination arm and in 40% (20/50) of patients in the monotherapy arm. The 18-month RFS rates (95% CI) were 78.6% (69.0%, 85.6%) vs 62.2% (46.9%,74.3%) in the combination and monotherapy arms respectively. There was also a statistically and clinically significant improvement in DMFS for the combination versus pembrolizumab monotherapy (HR = 0.347; 95% CI: (0.145, 0.828); 1-sided p-value 0.0063). Distant recurrence or death was reported in 8.4% (9/107) and 24% (12/50) of patients, with 18-month DMFS rates (95% CI) were 91.8% (84.2%, 95.8%) vs 76.8% (61.0%, 86.8%) in the combination and monotherapy arm, respectively. Conclusions: mRNA-4157 in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma significantly prolonged DMFS compared to pembrolizumab. These results provide further evidence that a personalized neoantigen approach is potentially beneficial for cancer patients. A phase 3 randomized study will be initiated in patients with melanoma. Clinical trial information: NCT03897881 .