Localized Melanoma Research Articles

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

Novel Curcumin-Resveratrol Solid Nanoparticles Synergistically Inhibit Proliferation of Melanoma Cells.

Polyphenols such as curcumin (Cur) and resveratrol (Res) have been recently shown to have potential to inhibit proliferation of highly aggressive melanoma cells. This study was designed to investigate the feasibility of a topical delivery system, using a solid lipid nanoparticles (SLNs) loaded delivery systems, that can enhance the skin penetration and anti-cancer efficacy of combination of these polyphenols. Negatively charged Cur-Res SLNs with a mean diameter of 180.2 ± 7.7nm were prepared using high shear homogenization method. Cur-Res SLNs were found to be stable up to 2weeks under 4°C. The in vitro release study showed that Res was released five time more than curcumin. The permeability of resveratrol was about 1.67 times that of curcumin from the SLN-gel formulation which was significantly (p < 0.05) lower than from SLN suspension. More than 70% of Cur-Res SLNs were bound to skin locally in a skin binding study suggesting potentially utility of Cur-Res SLNs in the treatment of localized melanoma. In fact, the electrical cell-substrate impedance sensing (ECIS) measurements suggested that Cur-Res combination has potential to stop cell migration of B16F10 melanoma cells. Furthermore, both, Cur-Res SLNs and Cur-Res solution at the ratio of 3:1 demonstrated a strong synergistic inhibition of SK-MEL-28 melanoma cell proliferation. Further evaluation of Cur-Res SLNs in vivo melanoma models are warranted to establish the clinical utility of Cur-Res formulations in melanoma therapy.

Real-world healthcare costs of localized and regionally advanced cutaneous melanoma in the Netherlands.

The aim of this study was to provide insight into real-world healthcare costs of patients initially diagnosed with localized or regionally advanced melanoma in three Dutch hospitals between 2003 and 2011. Patients were stratified according to their stage at diagnosis and recurrence status. Costs were calculated by applying unit costs to individual patient resource use and reported for the full disease course, the initial treatment episode, and treatment episodes for disease recurrence (stratified by type of recurrence). We included 198 patients with localized melanoma and 98 patients with regionally advanced melanoma. Total costs were much higher for patients with disease recurrence than for patients without disease recurrence: €20 007 versus €3032 for patients with localized melanoma and €19 519 versus €5951 for patients with regionally advanced melanoma. This was owing to the costs of disease recurrence because the costs of the initial treatment were comparable between patients with and without disease recurrence. Costs of disease recurrence were dependent on the type of recurrence: €4414, €4604, €8129 and €10 393 for a local recurrence, intralymphatic metastases, regional lymph node metastases and distant metastases, respectively. In conclusion, healthcare costs of patients with localized and regionally advanced melanoma were rather low for the initial treatment. Costs became, however, more substantial in case of disease recurrence. In the context of a rapidly changing treatment paradigm, it remains crucial to monitor treatment outcomes as well as healthcare expenditures.

Longitudinal study of prognostic factors for localized cutaneous melanoma in patients who have been disease-free for five years.

Most relapses in melanoma patients occur during the first five years after diagnosis. Identifying characteristics associated with recurrence after this period could help delineate guidelines, specifically for follow-up protocols. Objectives: The aim of this study was to identify the prognostic factors for relapse and death caused by melanoma in patients who have been disease-free for five years. We designed a longitudinal retrospective cohort to study Stage I/II cutaneous melanoma patients who have been free of disease for more than five years (late relapse cohort). Prognostic factors for disease-free and melanoma-specific survival were evaluated using the Kaplan-Meier method and Cox regression models. A series of 746 patients who had Stage I-II cutaneous melanoma and were free of disease for five years was selected. After a median follow-up of 64 months (124 months since melanoma diagnosis), 51 (6.8%) patients relapsed and 18 (2.4%) died from melanoma. Acral location and presence of ulceration, as well as intermediate growth rate (0.11-0.50 mm/month), were significantly associated with relapse or death due to melanoma. The initial recurrence site was associated with distant metastasis in 48% of the cases. In this study, we have identified melanoma characteristics in patients who have been disease-free for five years that may allow us to establish groups at increased risk of relapse or death due to melanoma, which could be helpful for melanoma management.

A multicentre study of naevus-associated melanoma vs. de novo melanoma, tumour thickness and body site differences.

Whether melanoma in histological contiguity with a naevus [naevus-associated melanoma (NAM)] is distinctly different from melanoma arising de novo remains unclear. To determine whether the characteristics of de novo melanoma differ from NAM and are not due to naevus obliteration in thicker tumours. We conducted a multicentre retrospective study of de novo melanoma and NAM in seven referral centres in Europe, Australia and the USA between 2006 and 2015. In a total of 9474 localized melanomas, de novo melanoma was associated with thicker tumours and body site differences compared with NAM. In the subset of T1 melanomas (n=5307), similar body site differences were found in multivariate analysis by body site. When compared with NAM, de novo melanoma was more likely to affect older individuals (≥ 70years) when located on the head/neck [odds ratio (OR) 4·65, 95% confidence interval (CI) 2·55-8·46], the trunk (OR 1·82, 95% CI 1·40-2·36) or the upper extremity (OR 1·69, 95% CI 1·14-2·50), was more likely to affect female patients when located on the lower extremities (OR 1·36, 95% CI 1·03-1·80), and was more likely to be of the nodular melanoma subtype (OR 2·23, 95% CI 1·14-4·35) when located on the trunk. De novo melanoma was less likely to have regression present compared with NAM. Clinicopathological and body site differences between de novo melanoma and NAM support the divergent pathway model of development. These differences were also found in thin melanomas, suggesting that de novo melanomas are different from NAM and their differences are not due to the obliteration of naevus remnants in thicker tumours.

ASO Author Reflections: Cutaneous Melanoma as Model System for the Obesity Paradox in Cancer.

Appreciation of the relationship between obesity and cancer has skyrocketed since the early 2000s. Though obesity is convincingly associated with an increased risk of at least 13 different cancers, the relationship between obesity and cutaneous melanoma remains unclear. Here, we reflect on our research into the relationship between obesity and clinically localized melanoma presented in the accompanying article, "The Impact of Obesity on Surgically Treated Locoregional Melanoma" (in press). The data presented are consistent with an "obesity paradox" in which obesity is linked to thicker melanomas and later stage at presentation without affecting survival. Given the complexity of the relationship with obesity, we propose that cutaneous melanoma is an excellent model system to investigate the role of obesity in different aspects of tumor biology and care, including risk of tumor development, tumor invasion, surgical outcomes, and response to systemic therapy.

Association of the Affordable Care Act's Medicaid expansion with the diagnosis and treatment of clinically localized melanoma: A National Cancer Database study

TheAffordable Care Act's Medicaid expansion is associated with earlier diagnosis and improved care among lower socioeconomic status populations with cancer, but its impact on melanoma is undefined. To determine the association of Medicaid expansion with stage of diagnosis and use of sentinel lymph node biopsy in nonelderly adult patients with newly diagnosed clinically localized melanoma. Quasi-experimental, difference-in-differences retrospective cohort analysis using data from the National Cancer Database from 2010 to 2017. Patients from expansion versus nonexpansion states and diagnosed before (2010-2013) versus after (2014-2017) expansion were identified. Of 83,322 patients, 46.6% were female, and the median age was 55years (interquartile range, 49-60). After risk adjustment, Medicaid expansion was associated with a decrease in the diagnosis of T1b stage or higher melanoma (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.98; P=.011) and decrease in uninsured status (OR, 0.61; 95% CI, 0.52-0.72; P<.001) but was not associated with a difference in sentinel lymph node biopsy performance when indicated (OR, 1.06; 95% CI, 0.95-1.20; P=.29). Retrospective study using a national database. In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors.

Differences Between Recommended Surgical Margins and Measured Histological Margins in Malignant Melanoma In Situ and Malignant Melanomas.

Wide local excision (WLE) using appropriate surgical margins is the standard surgical management for malignant melanoma in situ (MMIS) and primary cutaneous malignant melanoma (MM). The actual width of the histologic margins is frequently not assessed, whereas narrow histologic margins are associated with an increase in local melanoma recurrence. Our objective was to analyze the actual measured histological margins of WLE specimens of MMIS and MM cases and compare them with their recommended surgical margins. A retrospective study of formalin fixed specimens of MMIS and invasive MM treated with WLE from a large university-affiliated dermatopathology laboratory was conducted. Among a total of 164 MMIS and 128 MM cases, 14 MMIS (8.5%) and 7 MM (5.9%) had positive lateral margins. The median histologic margin for MMIS, after a 15% tissue shrinkage adjusted, was 2.7 mm [1.3-3.9] for LM type and 3.9 mm [2.3-5.6] for non-LM type, in contrast to the recommended 5-mm margin. In 96 MM of T1 type (≤1.0 mm), the median adjusted histologic margin was 6.7 mm [3.5-9.1] in contrast to the recommended 10-mm margin. These results show that measured and adjusted median histologic margins in WLE specimens in both MMIS and MM of T1 type were significantly narrower than the recommended surgical margins, regardless of anatomic location. These differences are concerning, whether they reflect clinicians' intentional or unintentional deviation from recommended guidelines.

Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors

BackgroundDespite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence...

Cell membrane inspired nano-shell enabling long-acting Glucose Oxidase for Melanoma starvation therapy via microneedles-based percutaneous delivery

Rationale: Glucose oxidase (GOx) has gained tremendous research interest recently as a glucose-consuming enzyme for tumor starvation therapy, while its in vivo applications are strictly limited by rapid deactivation, as well as side effects of non-specific catalysis.Methods: To address these issues, here we report a protective nano-shell to encapsule GOx for localized melanoma therapy delivered by dissolving microneedles (MNs). Inspired by cell membrane that separates and protects cell organelles and components from outside environment while selectively ingesting nutrition sources, we designed polydopamine (PDA)-structured nano-shell to allow free transportation of glucose for catalytic reaction, while impede the penetration of GOx, proteinase, and other GOx-deactivating macromolecules across the shell membrane.Results: GOx was well protected in core layer with persistent catalytic activity for at least 6 d under various biological matrixes (e.g., PBS, serum, and cell lysate) and surviving different harsh conditions (e.g., acid/base treatments, and proteinase-induced degradation). Such long-acting nano-catalyst can be easily integrated into MNs as topical delivery carrier for effective glucose consumption in melanoma tissue, achieving significant tumor growth inhibition via starvation therapy with minimized side effects as compared to systemic administration.Conclusion: This work provides an elegant platform for in vivo delivery of GOx, and our cell-mimicking nano-system can also be applied for other enzyme-based therapeutics.

Germline variants are associated with increased primary melanoma tumor thickness at diagnosis.

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness.To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness.The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry.We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.

Abstract PO-059: COVID-19 in melanoma patients: Spanish register

Abstract Background: The COVID-19 pandemic has produced devastating effects on the health care system, also affecting cancer patient care. When the pandemic reached Spain by the end of February 2020, the scarce data about COVID-19 infection in cancer patients pointed out a higher risk of complications due to cancer diagnosis and also to cancer therapies. These conjectures led to concerns about hospital follow-up and cancer therapies of cancer patients. More recent studies have included a higher number of patients, but heterogeneous according to cancer type and tumor stage, with few melanoma patients recorded. Given that different tumor types are associated with specific comorbidities that have a known impact on COVID-19 evolution, analysis of COVID-19 by cancer types is mandatory. Similarly, analysis by tumor stage is relevant, as advanced cases could have different responses to viral infection due to tumor-related immunosuppression and general condition deterioration. Methods: In Spain we have completed a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020 to June 8th, 2020. Patients with a previous diagnosis of melanoma, presenting with Sars-Cov-2 infection to our network of hospitals, were eligible for enrollment. A prospective observational study with a case registry followed by a retrospective analysis of patient data has been performed. Results: 64 patients have been included. Median age is 68 years (range 6 to 95 years), 22 (34%) patients are females, and 35 (55%) patients have stage IV melanoma. Twenty-one (33%) patients were on active anticancer treatment with anti PD-1 antibodies, 19 (30%) patients with BRAF plus MEK inhibitors, and 24 (37%) patients were not on active treatment. Asymptomatic/paucisymptomatic evolution was recorded in 19 (30%) patients and mild severity in 13 (20%) patients, not requiring hospital admission by COVID-19. Serious and life-threatening complications were recorded in 18 (28%) and 14 (22%) patients, respectively, including 28 (44%) patients who required oxygen therapy and 3 (5%) patients who had ICU admission. COVID-19 episode is resolved in 55 cases, including 34 (53%) patients cured, eight (12%) patients who have died due to melanoma progression, and 13 (20%) patients due to COVID-19. The median age of patients who died from COVID-19 was 74 years (range 49 to 91), while for those cured it was 64 years (range 6 to 95); 85% of patients who died were males, while this rate decreased to 62% for those cured. The mortality rate from COVID-19 was 20% for both stage IV and localized melanoma, while according to melanoma treatment it was 21%, 16%, and 21% for immunotherapy, BRAF plus MEK inhibitors, and for those who were not undergoing active cancer treatment, respectively. Conclusion: Our results show that the risk of death in melanoma patients is higher in males and older patients, and it is similar according to tumor stage and melanoma therapy. The impact of cancer diagnosis and treatments on COVID-19 evolution is lower than previously expected. Citation Format: Maria Gonzalez-Cao, Cristina Carrera, Juan Francisco Rodriguez Moreno, Pedro Rodriguez-Jiménez, Mónica Antoñanzas Basa, Marta Feito Rodríguez, Teresa Puertolas, Eva Muñoz, José Luis Manzano, Ivan Marquez-Rodas, Juan Martín-Liberal, Ainara Soria, Pilar Lopez Criado, Almudena García Castaño, Aram Boada, Pablo Ayala de Miguel, Susana Puig, Guillermo Crespo, Pablo Luna Fra, Cristina Aguayo Zamora, Jesús Gardeazabal, Cayetana Maldonado Seral, Ana Drozdowskyj, Mariano Provencio, Alfonso Berrocal. COVID-19 in melanoma patients: Spanish register [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-059.

The role of topical imiquimod in melanoma cutaneous metastases: A critical review of the literature.

Despite of the emerging new systemic and local oncologic treatments (immunotherapy and checkpoint inhibitors, oncolytic viral treatments and injected immunostimulants) the management of skin melanoma metastasis can be still challenging. The main aim of this review was to assess the efficacy and the role of imiquimod in local metastatic melanoma disease. An extensive literature review was performed from September 2000 to March 2020 using PubMed, MEDLINE, Embase, and Cochrane Library databases. Selected articles regarded topical imiquimod, its mode of action as an antitumoral agent and its applications in melanoma metastases treatment. We analyzed a total of 18 published article of clinical cases and small case series and five studies: two retrospective large case series, two Phase I and II clinical trials and one cohort non randomized study. Generally, the treatment is safe and well tolerated. Imiquimod lead to an unstable locoregional control. The use of topical imiquimod for the treatment of MM cutaneous metastases should be considered in selected cases and in palliative settings.

Is the neutrophil-to-lymphocyte ratio a useful prognostic indicator in melanoma patients?

The neutrophil-to-lymphocyte ratio (NLR) is gaining traction as a biomarker with utility in a variety of malignancies including melanoma. Intact lymphocyte function is necessary for tumor surveillance and destruction, and neutrophils play a role in suppressing lymphocyte proliferation and in the induction of lymphocyte apoptosis. Early research in melanoma indicates that in high-risk localized melanoma, a high NLR is correlated with worse overall and disease-free survival. Similarly, in metastatic melanoma treated with both metastasectomy and immunotherapies, an elevated NLR is predictive of shortened overall survival and progression-free survival. Future studies incorporating NLR into more traditional melanoma prognostic markers while employing more granular outcomes, are needed to realize the full potential of NLR.

Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma

The performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized. To systematically assess the performance of commercially available GEP tests in patients with American Joint Committee on Cancer (AJCC) stage I or stage II disease. For this systematic review and meta-analysis, comprehensive searches of PubMed/MEDLINE, Embase, and Web of Science were conducted on December 12, 2019, for English-language studies of humans without date restrictions. Two reviewers identified GEP external validation studies of patients with localized melanoma. After exclusion criteria were applied, 7 studies (8%; 5 assessing DecisionDx-Melanoma and 2 assessing MelaGenix) were included. Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation. Proportion of patients with or without melanoma recurrence correctly classified by the GEP test as being at high or low risk. In the 7 included studies, a total of 1450 study participants contributed data (age and sex unknown). The performance of both GEP tests varied by AJCC stage. Of patients tested with DecisionDx-Melanoma, 623 had stage I disease (6 true-positive [TP], 15 false-negative, 61 false-positive, and 541 true-negative [TN] results) and 212 had stage II disease (59 TP, 13 FN, 78 FP, and 62 TN results). Among patients with recurrence, DecisionDx-Melanoma correctly classified 29% with stage I disease and 82% with stage II disease. Among patients without recurrence, the test correctly classified 90% with stage I disease and 44% with stage II disease. Of patients tested with MelaGenix, 88 had stage I disease (7 TP, 15 FN, 15 FP, and 51 TN results) and 245 had stage II disease (59 TP, 19 FN, 95 FP, and 72 TN results). Among patients with recurrence, MelaGenix correctly classified 32% with stage I disease and 76% with stage II disease. Among patients without recurrence, the test correctly classified 77% with stage I disease and 43% with stage II disease. The prognostic ability of GEP tests among patients with localized melanoma varied by AJCC stage and appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients.

Paclitaxel skin delivery by micelles-embedded Carbopol 940 hydrogel for local therapy of melanoma.

Local application of anticancer drugs provides a potential mode of chemotherapy for cutaneous melanoma with high compliance. However, the efficiency of drug delivery is highly limited by the physiological barrier from the skin to the tumor, which can not achieve the desired therapeutic effect. In the study, we designed ibuprofen-modified methoxy poly (ethylene glycol)-poly (ethylene imine) polymer to prepare paclitaxel-loaded micelles (PTX-M) and Carbopol 940 hydrogel containing PTX-M (PTX-Gel) to improve skin paclitaxel delivery for the local melanoma treatment. The PTX-M performed well both in the skin penetration and retention study. FT-IR analysis showed that PTX-M or PTX-Gel mainly changed the spatial structure of skin lipid and keratin, thus increasing the fluidity of lipid molecules in the stratum corneum, and the polymer was positively charged to enhance the skin permeation and deposition. Moreover, the positive charge also promoted the cellular uptake of PTX-M in B16 melanoma, resulting in better in vitro cytotoxicity of PTX-M to B16 cells Taxol®. As for in vivo against B16 cells solid tumor test, the Taxol® plus PTX-M/Gel group showed preferable anticancer activity than Taxol® alone.

Listing Malignant Melanoma Patients for Renal Transplantation

BackgroundMelanoma is an immune responsive malignancy and the need for immunosuppression for successful transplantation may lead to recurrent disease. The recommended waiting time is unknown with various groups recommending anywhere from no wait to 5 years. MethodsIn this single-center, retrospective observational study all kidney transplant recipients’ charts from 1991 to 2015 were reviewed for a diagnosis of melanoma before transplantation. The charts were reviewed for the clinical characteristics of melanoma pre transplantation, induction immunosuppression, maintenance immunosuppression, graft function, death, and recurrence of melanoma. ResultsThirteen patients with a history of melanoma underwent kidney transplantation during this period. Recipients had been in remission for an average of 7.0 years (range, 10 months to 20 years, median 6 years). Approximately 61.5% received a living donor transplant, antithymocyte globulin was administered in 23.1% of recipients, and the remaining 76.9% received basiliximab. Melanoma recurred in 1 patient (7.7%). Maintenance immunosuppression varied, but only 2 patients remained on standard triple therapy with prednisone, calcineurin inhibitor, and antimetabolite therapy. Average follow-up time since transplant was 7.5 years, with 1 patient death 9 years post transplant from sepsis. ConclusionIn conclusion, with our center demonstrates safety of kidney transplantation in patients with a prior history of localized melanoma and shorter waiting time. In malignant melanoma stage 0 and 1, waiting the recommended 5 years from the time of remission to kidney transplantation should be reconsidered.

Sentinel Lymph Node Biopsy Is Prognostic in Thickest Melanoma Cases and Should Be Performed for Thick Melanomas.

Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. The Sentinel Lymph Node Working Group database was queried for thick (> 4mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). There were 1235 patients. Median follow-up was 28months. Median thickness was 5.9mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P < 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas > 4-8mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P < 0.0001). For melanomas > 8mm, only SLN metastasis significantly predicted MSS (> 8-12mm: HR 3.93, 95% CI 2.00-7.73, P < 0.0001; > 12mm: HR 3.58, 95% CI 1.56-8.22, p < 0.0027). Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

Molecular profiling and clinical characteristic of malignant melanoma in younger patients.

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.

Lifestyle among long-term survivors of cancers in young adulthood

PurposeTo investigate lifestyle in a population-based sample of long-term (≥ 5 years since diagnosis) young adult cancer survivors (YACSs), and explore factors associated with not meeting the lifestyle guidelines for physical activity (PA), body mass index (BMI), and smoking.MethodsYACSs (n = 3558) diagnosed with breast cancer (BC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or localized malignant melanoma (MM) between the ages of 19 and 39 years and treated between 1985 and 2009 were invited to complete a mailed questionnaire. Survivors of localized MM treated with limited skin surgery served as a reference group for treatment burden.ResultsIn total, 1488 YACSs responded (42%), and 1056 YACSs were evaluable and included in the present study (74% females, average age at survey 49 years, average 15 years since diagnosis). Forty-four percent did not meet PA guidelines, 50% reported BMI ≥ 25 and 20% smoked, with no statistically significant differences across diagnostic groups. Male gender, education ≤ 13 years, comorbidity, lymphedema, pain, chronic fatigue, and depressive symptoms were associated with not meeting single and/or an increasing number of lifestyle guidelines.ConclusionA large proportion of long-term YACSs do not meet the lifestyle guidelines for PA, BMI, and/or smoking. Non-adherence to guidelines is associated with several late effects and/or comorbidities that should be considered when designing lifestyle interventions for YACSs.