Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma.

Introduction: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) predominantly affect the head and neck areas in elderly patients, presenting as challenging ill-defined pigmented lesions with indistinct borders. Surgical margin determination for complete removal remains intricate due to these characteristics. Morphological examination of surgical margins is the key form of determining successful treatment in LM/LMM and underpin the greater margin control provided through the Slow Mohs micrographic surgery (SMMS) approach. Recent assessments have explored the use of immunohistochemistry (IHC) markers, such as Preferentially Expressed Antigen in Melanoma (PRAME), to aid in LM/LMM and margin evaluation, leveraging the selectivity of PRAME labelling in malignant melanocytic neoplasms. Methods: A Novel double-labelling (DL) method incorporating both PRAME and MelanA IHC was employed to further maximise the clinical applicability of PRAME in the assessment of LM/LMM in SMMS biopsies. The evaluation involved 51 samples, comparing the results of the novel DL with respective single-labelling (SL) IHC slides. Results: The findings demonstrated a significant agreement of 96.1% between the DL method and SL slides across the tested samples. The benchmark PRAME SL exhibited a sensitivity of 91.3% in the SMMS specimens and 67.9% in histologically confirmed positive margins. Discussion: This study highlights the utility of PRAME IHC and by extension PRAME DL as an adjunctive tool in the assessment of melanocytic tumours within staged excision margins in SMMS samples.

Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data.

PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed. RESULTS: In all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival. CONCLUSION: A high number of concurrent medications was associated with poor clinical outcomes.

Immunohistochemistry for Diagnosing Melanoma in Older Adults.

Importance: Pathologic assessment to diagnose skin biopsies, especially for cutaneous melanoma, can be challenging, and immunohistochemistry (IHC) staining has the potential to aid decision-making. Currently, the temporal trends regarding the use of IHC for the examination of skin biopsies on a national level have not been described. Objective: To illustrate trends in the use of IHC for the examination of skin biopsies in melanoma diagnoses. Design, Setting, and Participants: A retrospective cross-sectional study was conducted to examine incident cases of melanoma diagnosed between January 2000 and December 2017. The analysis used the SEER-Medicare linked database, incorporating data from 17 population-based registries. The study focused on incident cases of in situ or malignant melanoma of the skin diagnosed in patients 65 years or older. Data were analyzed between August 2022 and November 2023. Main Outcomes and Measures: The main outcomes encompassed the identification of claims for IHC within the month of melanoma diagnoses and extending up to 14 days into the month following diagnosis. The SEER data on patients with melanoma comprised demographic, tumor, and area-level characteristics. Results: The final sample comprised 132 547 melanoma tumors in 116 117 distinct patients. Of the 132 547 melanoma diagnoses meeting inclusion criteria from 2000 to 2017, 43 396 cases had accompanying IHC claims (33%). Among these cases, 28 298 (65%) were diagnosed in male patients, 19 019 (44%) were diagnosed in patients aged 65 years to 74 years, 16 444 (38%) in patients aged 75 years to 84 years, and 7933 (18%) in patients aged 85 years and older. In 2000, 11% of melanoma cases had claims for IHC at or near the time of diagnosis. This proportion increased yearly, with 51% of melanoma cases having associated IHC claims in 2017. Increasing IHC use is observed for all stages of melanoma, including in situ melanoma. Claims for IHC in melanomas increased in all 17 SEER registries but at different rates. In 2017, the use of IHC for melanoma diagnosis ranged from 39% to 68% across registries. Conclusions and Relevance: Considering the dramatically rising and variable use of IHC in diagnosing melanoma by pathologists demonstrated in this retrospective cross-sectional study, further investigation is warranted to understand the clinical utility and discern when IHC most improves diagnostic accuracy or helps patients.

Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial.

INTRODUCTION: In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC-IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis. METHODS: A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed. RESULTS: Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most. CONCLUSION: Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC-IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.

Decoding the synergistic potential of MAZ-51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals.

Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment-producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor-beta 1 (TGF-ß1), vascular endothelial growth factor-C (VEGF-C) and C-X-C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3-(4-dimethylaminonaphthelen-1-ylmethylene)-1,3-dihydroindol-2-one) MAZ-51 is an indolinone-based molecule that inhibits VEGF-C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR-3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well-being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun-safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy.

Implementing systematic melanoma risk assessment and risk-tailored surveillance in a skin cancer focussed dermatology clinic: A qualitative study of feasibility and acceptability to patients and clinic staff.

BACKGROUND: International bodies recommend that melanoma risk assessment should be integrated into skin cancer care provision, but evidence to support implementation is lacking. AIM: To explore the acceptability and feasibility of implementing personalised melanoma risk assessment and tailored patient education and skin surveillance within routine clinical care. METHODS: This prospective qualitative implementation study was informed by the Theoretical Framework of Acceptability (TFA). Personalised, systematic melanoma risk assessment was implemented in the dermatology clinic at the Melanoma Institute Australia, Sydney, Australia February-May 2021. Pre- and post-implementation observations and semi-structured interviews with patients and staff were conducted (September 2020-March 2021). Observational notes and interview transcript data were analysed thematically using the TFA as a classifying framework. RESULTS: A total of 37 h of observations were made, and 29 patients and 12 clinic staff were interviewed. We found that the delivery of personalised melanoma risk estimates did not impact on patient flow through the clinic. Dermatologists reported that the personalised risk information enhanced their confidence in assessing patient risk and recommending tailored surveillance schedules. Most patients reported that the risk assessment and tailored information were a beneficial addition to their care. Among patients whose risk deviated from their expectations, some reported feeling worried, confused or mistrust in the risk information, including those at lower risk who were recommended to decrease surveillance frequency. CONCLUSIONS: It is feasible and acceptable to patients and clinic staff to calculate and deliver personalised melanoma risk information and tailored surveillance as part of routine clinical care within dermatology clinics.

Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy.

Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P =  0.038) and SFI with anti-PD-1 therapy ( P =  0.006). Both NLR and dNLR were associated with OS ( P =  0.038 and P =  0.046, respectively) and SFI ( P =  0.001 and P =  0.019, respectively). NLR was also associated with immunotherapy response ( P =  0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.

Assessment of Social Vulnerabilities of Care and Prognosis in Adult Ocular Melanomas in the US.

BACKGROUND: Prior works have studied the impact of social determinants on various cancers but there is limited analysis on eye-orbit cancers. Current literature tends to focus on socioeconomic status and race, with sparse analysis of interdisciplinary contributions. We examined social determinants as measured by the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI), quantifying eye and orbit melanoma disparities across the United States. METHODS: A retrospective review of 15,157 patients diagnosed with eye-orbit cancers in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017 was performed, extracting 6139 ocular melanomas. SVI scores were abstracted and matched to SEER patient data, with scores generated by weighted averages per population density of county's census tracts. Primary outcome was months survived, while secondary outcomes were advanced staging, high grading, and primary surgery receipt. RESULTS: With increased total SVI score, indicating more vulnerability, we observed significant decreases of 23.1% in months survival for melanoma histology (p < 0.001) and 19.6-39.7% by primary site. Increasing total SVI showed increased odds of higher grading (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.43) and decreased odds of surgical intervention (OR 0.94, 95% CI 0.92-0.96). Of the four themes, higher magnitude contributions were observed with socioeconomic status (26.0%) and housing transportation (14.4%), while lesser magnitude contributions were observed with minority language status (13.5%) and household composition (9.0%). CONCLUSIONS: Increasing social vulnerability, as measured by the CDC SVI and its subscores, displayed significant detrimental trends in prognostic and treatment factors for adult eye-orbit melanoma. Subscores quantified which social determinants contributed most to disparities. This lays groundwork for providers to target the highest-impact social determinant for non-clinical factors in patient care.

Health Economic Consequences Associated With COVID-19-Related Delay in Melanoma Diagnosis in Europe.

Importance: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet. Objective: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe. Design, Setting, and Participants: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022. Exposure: COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks. Main Outcomes and Measures: Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure. Results: There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario. Conclusions and Relevance: This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

Assessment of Autophagy in Tumor Cells of Human Skin Melanoma of Different Stages.

High levels of autophagy can increase the viability of tumor cells as well as their resistance to chemotherapy. Evaluation of the dynamics of autophagy processes at different stages of carcinogenesis can extend our understanding of melanoma pathogenesis to develop new therapeutic approaches. We performed a comparative study of tumor cell autophagy in stages II and III human skin melanoma. Tumor cells were characterized by high content of structures associated with autophagy (autophagosomes and autolysosomes). In stage III melanoma characterized by the presence of regional metastases in the lymph nodes, tumor cells showed higher expression of the autophagy marker protein LC3beta in comparison with stage II melanoma cells, which can indicate the involvement of autophagy processes in tumor progression and the formation of metastases in the lymph nodes.

Disparities in the Receipt of Systemic Treatment in Metastatic Melanoma.

BACKGROUND: In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients. METHODS: We performed a retrospective review of patients in the National Cancer Database for patients with stage IV melanoma from 2 time periods: 2004-2010 and 2016-2020, distinguishing between those who received systemic therapy and those who did not. We investigated the rates and factors associated with treatment omission. We employed Kaplan-Meier analysis to explore the impact of treatment on overall survival. RESULTS: A total of 19,961 patients met the inclusion criteria: 7621 patients were diagnosed in 2004-2010 and 12,340 patients in 2016-2020, of whom 54.9% and 28.3% did not receive systemic treatment, respectively. The rate of "no treatment" has decreased to a plateau of ∼25% in 2020. Median overall survival was improved with treatment in both time periods (2004-2010: 8.8 vs. 5.6 mo [ P <0.05]; and 2016-2020: 25.9 vs. 4.3 mo [ P <0.05]). Nonmedical factors associated with the omission of treatment in both periods included low socioeconomic status, Medicaid or no health insurance, and treatment at low-volume centers. In the period from 2016 to 2020, patients treated at nonacademic programs were also less likely to receive treatment. CONCLUSIONS: Systemic therapies significantly improve survival for patients with metastatic melanoma, but significant disparities exist with their receipt. Local efforts are needed to ensure all patients benefit from these revolutionary treatments.

Photoacoustic imaging for cutaneous melanoma assessment: a comprehensive review.

Significance: Cutaneous melanoma (CM) has a high morbidity and mortality rate, but it can be cured if the primary lesion is detected and treated at an early stage. Imaging techniques such as photoacoustic (PA) imaging (PAI) have been studied and implemented to aid in the detection and diagnosis of CM. Aim: Provide an overview of different PAI systems and applications for the study of CM, including the determination of tumor depth/thickness, cancer-related angiogenesis, metastases to lymph nodes, circulating tumor cells (CTCs), virtual histology, and studies using exogenous contrast agents. Approach: A systematic review and classification of different PAI configurations was conducted based on their specific applications for melanoma detection. This review encompasses animal and preclinical studies, offering insights into the future potential of PAI in melanoma diagnosis in the clinic. Results: PAI holds great clinical potential as a noninvasive technique for melanoma detection and disease management. PA microscopy has predominantly been used to image and study angiogenesis surrounding tumors and provide information on tumor characteristics. Additionally, PA tomography, with its increased penetration depth, has demonstrated its ability to assess melanoma thickness. Both modalities have shown promise in detecting metastases to lymph nodes and CTCs, and an all-optical implementation has been developed to perform virtual histology analyses. Animal and human studies have successfully shown the capability of PAI to detect, visualize, classify, and stage CM. Conclusions: PAI is a promising technique for assessing the status of the skin without a surgical procedure. The capability of the modality to image microvasculature, visualize tumor boundaries, detect metastases in lymph nodes, perform fast and label-free histology, and identify CTCs could aid in the early diagnosis and classification of CM, including determination of metastatic status. In addition, it could be useful for monitoring treatment efficacy noninvasively.

Functional assay for assessment of pathogenicity of BAP1 variants.

BACKGROUND: Pathogenic germline variants in BRCA1-Associated Protein 1 (BAP1) cause BAP1 tumor predisposition syndrome (BAP1-TPDS). Carriers run especially a risk of uveal (UM) and cutaneous melanoma, malignant mesothelioma, and clear cell renal carcinoma. Approximately half of increasingly reported BAP1 variants lack accurate classification. Correct interpretation of pathogenicity can improve prognosis of the patients through tumor screening with better understanding of BAP1-TPDS. METHODS: We edited five rare BAP1 variants with differing functional characteristics identified from patients with UM in HAP1 cells using CRISPR-Cas9 and assayed their effect on cell adhesion/spreading (at 4 h) and proliferation (at 48 h), measured as cell index (CI), using xCELLigence real-time analysis system. RESULTS: In BAP1 knockout HAP1 cultures, cell number was half of wild type (WT) cultures at 48 h (p = 0.00021), reaching confluence later, and CI was 78% reduced (p < 0.0001). BAP1-TPDS-associated null variants c.67+1G>T and c.1780_1781insT, and a likely pathogenic missense variant c.281A>G reduced adhesion (all p ≤ 0.015) and proliferation by 74%-83% (all p ≤ 0.032). Another likely pathogenic missense variant c.680G>A reduced both by at least 50% (all p ≤ 0.032), whereas cells edited with likely benign one c.1526C>T grew similarly to WT. CONCLUSIONS: BAP1 is essential for optimal fitness of HAP1 cells. Pathogenic and likely pathogenic BAP1 variants reduced cell fitness, reflected in adhesion/spreading and proliferation properties. Further, moderate effects were quantifiable. Variant modelling in HAP1 with CRISPR-Cas9 enabled functional analysis of coding and non-coding region variants in an endogenous expression system.

Significance of Social Determinants of Health in Tumor Presentation, Hospital Readmission, and Overall Survival in Ocular Oncology.

PURPOSE: To evaluate the association between social determinants of health (SDH) with presentation and outcomes in patients with ocular cancer. METHODS: The National Cancer Database was queried for primary clinical tumor (cT) classifications of T1 to T4 N0M0 uveal melanoma, conjunctival melanoma, or retinoblastoma diagnosed between January 2006 and December 2017. Pearson χ2 analysis assessed differences in SDH-related characteristics between cancer cohorts. Binary logistic regression with adjusted odds ratios (aORs) and multivariate Cox proportional hazards ratios (HRs) with 95% confidence intervals (CIs) were performed. DESIGN: Cross-sectional with a nationally representative sample. RESULTS: Three thousand nine hundred sixty-eight uveal melanoma cases, 352 conjunctival melanoma cases, and 480 retinoblastoma cases were included. Differences in race, primary payer status, income quartile, population density, facility location, Charlson-Deyo comorbidity score, history of malignancy, cT classification at presentation, surgical treatment, radiotherapy, chemotherapy, 30-day readmission, and overall survival (OS) were observed among the cancers. Female sex (aOR 0.819 [95% CI 0.689-0.973]) and top income quartile (aOR 0.691 [95% CI 0.525-0.908]) had decreased likelihood of advanced cT classification at presentation. No insurance (aOR 1.736 [95% CI 1.159-2.601]) and Medicaid primary payer status (aOR 1.875 [95% CI 1.323-2.656]) had increased likelihood of advanced cT classification. Patients in rural areas (aOR 7.157 [95% CI 1.875-27.320]) were more likely to be readmitted within 30 days after initial treatment. Increased age was associated with decreased 5-year OS (HR 1.040 [95% CI 1.033-1.047]). CONCLUSIONS: SDH may influence advanced cT classification at presentation and 30-day readmission compared with OS in patients with ocular cancer, highlighting the need for ophthalmologists and public health efforts to address disparities in SDH.

Uveal melanoma in African Americans: Diagnostic challenges.

Uveal melanoma (UM) is uncommon in African Americans. Owing to its rarity, UM may not be suspected in African Americans leading to delayed diagnosis. In addition, socioeconomic factors may also play a role in delayed diagnosis. Clinical and ultrasonographic features may be atypical due to racial pigmentation, necessitating diagnostic fine needle aspiration biopsy. Herein, we report an illustrative case series of 12 African Americans with UM highlighting clinical features and diagnostic challenges.

Immunotherapy Treatment Disparities: A Texas Cancer Registry Analysis of Patients with Cutaneous Melanoma.

As the deadliest form of skin cancer, advanced-stage melanoma is a devastating disease. Encouragingly, with the introduction of immunotherapy, the overall survival of metastatic melanoma has improved drastically. However, access to novel immunotherapeutic drugs is not universal for all patients. Herein, we examined the association between various sociodemographic factors and the likelihood of using immunotherapy for melanoma treatment. This is a retrospective cohort study using the Texas Cancer Registry data for the years 2011-2018. Multivariable regression analysis was done to evaluate the association between patient characteristics and likelihood of receipt of immunotherapy. The association between sociodemographic factors and likelihood of presentation with metastasis at diagnosis was also examined. Having metastasis at diagnosis was strongly associated with higher odds of receiving immunotherapy (penalized adjusted OR 28.690, 95% CI 23.470-34.350, p < .0001). Compared to having private insurance, patients were less likely to receive immunotherapy if they were uninsured, had Medicare, or had missing/unknown insurance status (penalized adjusted OR's 0.700, 0.790, 0.130, p = .026, 0.027, and p < .0001 respectively). Results from our multivariate model highlighted several factors associated with a higher likelihood of presenting with metastatic disease which included Hispanic ethnicity and black race. Dermatologic disparities affecting the Hispanic population underscore the importance of targeted interventions to overcome community level barriers to melanoma treatment and diagnosis. This study highlights the need to further evaluate different insurance types and their effect on receipt of immunotherapy.

Analyzing County-level Social Vulnerabilities of Head and Neck Melanomas in the United States.

OBJECTIVES: Studies addressing social determinants of health (SDH) in head-neck melanomas (HNM) have only assessed incidence with increasing socioeconomic status. None have investigated a wider scope of SDH or their summed influence on affecting HNM prognosis and follow-up care. METHODS: This retrospective cohort study analyzed 374,138 HNM in adults from 1975 to 2017 from the NCI-Surveillance, Epidemiology, and End Results Program (NCI-SEER) database. Utilizing the NCI-SEER database, Social Vulnerability Index (SVI) scores were matched to county of residence upon diagnosis. Univariate linear regressions were performed on length of care (months of follow-up/surveyed) and prognosis (months survival) across various SDH/SVI scores of socioeconomic status, minority and language status, household composition, housing and transportation, and their total composite. RESULTS: With increasing overall SVI score, which indicates increasing social vulnerability, months of follow-up showed significant decreases ranging from 0.04% to 27.63% compared with the lowest vulnerability groups, with the highest differences in nodular melanomas and the lowest with malignant melanomas in giant pigmented nevi. Similarly, months survival significant decreases ranged from 0.19% to 39.84% compared with the lowest SVI scores, with the highest difference in epithelioid cell melanomas and the lowest in amelanotic melanoma. Comprising this overall score trend, decreases with socioeconomic status, minority-language status, household composition, and housing-transportation contributed differentially per histology subtype. CONCLUSIONS: Our data highlight significant negative trends in HNM prognosis and care with higher total social vulnerability while showing which SDH-themes quantifiably contribute more to these differences. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:185-190, 2024.

Cost-utility analysis of Pembrolizumab compared to other alternative immunotherapy and chemotherapy treatments for patients with advanced melanoma in Iran.

OBJECTIVES: Immunotherapy drugs like Pembrolizumab have shown significant improvements in treatment outcomes of advanced melanoma. This study aimed to evaluate the cost-utility of Pembrolizumab compared to other immunotherapy and chemotherapy drugs in the first-line treatment of advanced melanoma in Iran. METHODS: A partitioned-survival model, based on data from a recent randomized phase 3 study (KEYNOTE-006) and recent meta-analysis, was used to divide Overall survival (OS) time into Progression-free survival (PFS) and post-progression survival for Pembrolizumab, Nivolumab, Ipilimumab, Dacarbazine, Temozolomide, Carboplatin, and Paclitaxel combination. Quality Life Years (QALY) and Incremental Cost-Effectiveness Ratio (ICER) were considered as the final outcome. RESULTS: The ICER of Ipilimumab, Nivolumab, Nivolumab & Ipilimumab, and Pembrolizumab compared to Temozolomide was calculated as $40,365.53, $19,591.13, $24,578, and $47,324.2 per QALY, respectively. Scenario analysis demonstrated if the price of one vial of Nivolumab 100 is $90.51, each vial of Pembrolizumab is $119.20, and each vial of Ipilimumab is $101.54, they will be cost-effective in Iran. CONCLUSION: None of the immunotherapy drugs studied were found to be cost-effective when considering the cost-effectiveness threshold of $3,532. Therefore, a cost reduction of more than 90% in the prices of immunotherapy drugs would be necessary for them to be considered cost-effective in Iran.

Generation and comparison of 3D dosimetric reference datasets for COMS eye plaque brachytherapy using model-based dose calculations.

PURPOSE: A joint Working Group of the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) was created to aid in the transition from the AAPM TG-43 dose calculation formalism, the current standard, to model-based dose calculations. This work establishes the first test cases for low-energy photon-emitting brachytherapy using model-based dose calculation algorithms (MBDCAs). ACQUISITION AND VALIDATION METHODS: Five test cases are developed: (1) a single model 6711 125 I brachytherapy seed in water, 13 seeds (2) individually and (3) in combination in water, (4) the full Collaborative Ocular Melanoma Study (COMS) 16 mm eye plaque in water, and (5) the full plaque in a realistic eye phantom. Calculations are done with four Monte Carlo (MC) codes and a research version of a commercial treatment planning system (TPS). For all test cases, local agreement of MC codes was within ∼2.5% and global agreement was ∼2% (4% for test case 5). MC agreement was within expected uncertainties. Local agreement of TPS with MC was within 5% for test case 1 and ∼20% for test cases 4 and 5, and global agreement was within 0.4% for test case 1 and 10% for test cases 4 and 5. DATA FORMAT AND USAGE NOTES: Dose distributions for each set of MC and TPS calculations are available online (https://doi.org/10.52519/00005) along with input files and all other information necessary to repeat the calculations. POTENTIAL APPLICATIONS: These data can be used to support commissioning of MBDCAs for low-energy brachytherapy as recommended by TGs 186 and 221 and AAPM Report 372. This work additionally lays out a sample framework for the development of test cases that can be extended to other applications beyond eye plaque brachytherapy.

Effects of treatment methods on cutaneous melanoma related mortality and all-cause mortality in Texas: TCR-Medicare 2007-2017 database.

PURPOSE: The incidence of cutaneous melanoma is rising, and Melanoma related deaths are highest among people aged 65-74. Herein, we aim to understand the impact of novel and established melanoma treatment methods on CM related mortality and all-cause mortality. We further compared these effects among Hispanic and non-Hispanic Whites (NHW). METHODS: The data was extracted from the Texas Cancer Registry from 2007 to 2017. A Cox Proportional Hazard regression analysis was performed to assess treatment effect on melanoma mortality and all-cause mortality, with race-ethnicity as an effect modifier. RESULTS: A higher percentage of Hispanic patients presented with CM-related mortality (22.11%) compared to NHW patients (14.39%). In both the Hispanic and NHW, post-diagnosis radiation (HR = 1.610, 95% CI 0.984-2.634, HR = 2.348, 95% CI 2.082-2.648, respectively), post-diagnosis chemotherapy (HR = 1.899, 95% CI 1.085-3.322, HR = 2.035, 95% CI 1.664-2.489, respectively), and post-diagnosis immunotherapy (HR = 2.100, 95% CI 1.338-3.296, HR = 2.402, 95% CI 2.100-2.748) are each associated with an increased risk in CM-related mortality. Similar results were seen with post-diagnosis radiation (Hispanic HR = 1.640, 95% CI 1.121-2.400, NHW HR = 1.800, 95% CI 1.644-1.971), post-diagnostic chemotherapy (Hispanic HR = 1.457, 95% CI 0.898-2.364, NHW HR = 1.592, 95% CI 1.356-1.869), and post-diagnosis immunotherapy (Hispanic HR = 2.140, 95% CI 1.494-3.065, NHW HR = 2.190, 95% CI 1.969-2.435) with respect to all-cause mortality. Post-diagnosis surgery (HR = 0.581, 95% CI 0.395-0.856, HR = 0.622, 95% CI 0.571-0.678) had the opposite effect in CM-related mortality for Hispanics and NHWs respectively. CONCLUSION: Our results propose differences in all-cause and CM-only related mortality with separate treatment modalities, particularly with chemotherapy, radiation therapy and immunotherapy. In addition, this retrospective cohort study showed that health disparities exist in the Hispanic Medicare population of Texas with CM.