Association of type II diabetes mellitus with characteristics and outcomes for patients undergoing sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied. METHODS: Consecutive patients diagnosed with clinical stage I-II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007-2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis. RESULTS: Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non-insulin dependent [NID-T2DM]; n = 17 [15.3%] insulin dependent [ID-T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five-year cumulative incidence of melanoma recurrence was significantly higher for patients with ID-T2DM (46.7% ID-T2DM vs. 25.7% NID-T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID-T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5-year disease-specific survival was observed between groups. CONCLUSIONS: ID-T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted.

Sentinel lymph node biopsy in patients with clinical stage IIB/C cutaneous melanoma: A national cohort study.

BACKGROUND: Approval of adjuvant anti-programmed cell death protein 1 therapy for pathologic stage IIB/C cutaneous melanoma has led some to question the role of sentinel lymph node (SLN) biopsy in the clinical stage IIB/C disease. OBJECTIVE: To determine the prognostic significance of SLN staging on disease-specific survival (DSS) for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era. METHODS: A retrospective cohort study was performed evaluating patients who underwent excision of clinical stage IIB/C cutaneous melanoma using the Surveillance, Epidemiology, and End Results database (2004-2011). Patients who did and did not undergo SLN biopsy were compared using propensity matching, and among those who underwent SLN biopsy, matched patients were further stratified by SLN status (SLN positive [SLN+] or SLN negative [SLN-]). RESULTS: Of the 8562 patients evaluated, 6021 (70.3%) underwent SLN biopsy. SLN positivity was associated with significantly reduced 5-year DSS among matched patients who underwent SLN biopsy (47.1% SLN+ vs 75.5% SLN-; P < .001). Five-year DSS remained significantly different across matched T-stages: T3b (54.2% SLN+ vs 64.8% SLN-; P = .004), T4a (55.5% SLN+ vs 71.6% SLN-; P = .001), and T4b (38.6% SLN+ vs 60.9% SLN-; P < .001). LIMITATIONS: Retrospective study. CONCLUSION: For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information.

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

BACKGROUND: The Affordable 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. OBJECTIVE: 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. METHODS: 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. RESULTS: Of 83,322 patients, 46.6% were female, and the median age was 55 years (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). LIMITATIONS: Retrospective study using a national database. CONCLUSION: In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors.

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex.

BACKGROUND: The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored. METHODS: Patients who had clinically localized primary melanoma with a Breslow thickness of 0.76 mm or more and underwent sentinel lymph node (SLN) biopsy at our institution were identified. The association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated by using logistic regression. Overall survival (OS) was evaluated by TIL status and sex. RESULTS: Among 1367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (P = .71). SLN positivity was associated with TILs among men (brisk, 3.8%; nonbrisk, 16.9%; and absent, 26.6% [P < .001]). In contrast, there was no association between SLN positivity and TILs among women (P = .49). Interaction between brisk TILs and sex on SLN positivity was significant (P = .029). Among men, presence of brisk TILs was associated with prolonged OS (P = .038) but not after adjustment for SLN status (P = .42). There was no association between TIL status and OS among women. LIMITATIONS: Findings from this single-institution study have yet to be validated by other research groups. CONCLUSIONS: The implications of TILs in predicting SLN positivity appear to be more relevant for men than for women.

Risk factors for positive or equivocal margins after wide local excision of 1345 cutaneous melanomas.

BACKGROUND: Positive or equivocal margins after wide local excision (WLE) complicate surgical management of cutaneous melanoma. OBJECTIVE: To identify the frequency of and risk factors for positive or equivocal margins after WLE of cutaneous melanoma. METHODS: Retrospective, single-center, cross-sectional study of 1345 consecutive melanomas treated with WLE. RESULTS: The overall frequency of positive or equivocal margins was 4.2% (56/1345), ranging from 2.2% to 22.6%, depending on the size of the surgical margins, patient characteristics, biopsy history, and the clinicopathology of the melanoma. In descending order, independent risk factors associated with the greatest odds for positive or equivocal margins after multivariate analysis were noncompliance with recommended surgical margins (odds ratio [OR] 5.57, P = .002); anatomic location on the head, neck, hands, feet, genitals, or pretibial leg (OR 5.07, P < .001); histologic regression (OR 2.78, P = .007); in situ melanoma (OR 2.27, P = .011); multiple biopsies at the tumor site before WLE (OR 1.92 [per biopsy], P = .004); and increasing age (OR 1.049 [per year], P < .001). LIMITATIONS: This was a single-site, retrospective observational study. CONCLUSIONS: Clinicopathologic factors, especially location in cosmetically or functionally sensitive areas and noncompliance with recommended surgical margins, identified melanomas at increased risk for positive or equivocal margins after WLE.

Identification of Patients with Intermediate Thickness Melanoma at Low Risk for Sentinel Lymph Node Positivity.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is recommended for all patients with intermediate-thickness melanomas. We sought to identify such patients at low risk of SLN positivity. METHODS: All patients with intermediate-thickness melanomas (1.01-4 mm) undergoing SLN biopsy at a single institution from 1995-2011 were included in this retrospective cohort study. Univariate and multivariate logistic regression determined factors associated with a low risk of SLN positivity. Classification and regression tree (CART) analysis was used to stratify groups based on risk of positivity. RESULTS: Of the 952 study patients, 157 (16.5 %) had a positive SLN. In the multivariate analysis, thickness <1.5 mm (odds ratio [OR] 0.29), age ≥60 (OR 0.69), present tumor-infiltrating lymphocytes (OR 0.60), absent lymphovascular invasion (OR 0.46), and absent satellitosis (OR 0.44) were significantly associated with a low risk of SLN positivity. CART analysis identified thickness of 1.5 mm as the primary cut point for risk of SLN metastasis. Patients with a thickness of <1.5 mm represented 36 % of the total cohort and had a SLN positivity rate of 6.6 % (95 % confidence interval 3.8-9.4 %). In patients with melanomas <1.5 mm in thickness, the presence of additional low risk factors identified 257 patients (75 % of patients with <1.5 mm melanomas) in which the rate of SLN positivity was <5 %. CONCLUSIONS: Despite a SLN positivity rate of 16.5 % overall, substantial heterogeneity of risk exists among patients with intermediate-thickness melanoma. Most patients with melanoma between 1.01 and 1.5 mm have a risk of SLN positivity similar to that in patients with thin melanomas.

Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma.

Therapeutic immune checkpoint blockade for metastatic melanoma has been associated with vitiligo, pruritus and morbilliform eruptions. Reports of other autoimmune skin disease in this setting are rare. We sought to expand the spectrum of cutaneous immune-mediated effects related to immune checkpoint inhibitor therapy. In this report, we describe two unusual cutaneous reactions related to checkpoint inhibitor therapy, namely bullous pemphigoid (BP) and dermatitis herpetiformis. The development of BP and dermatitis herpetiformis in the context of checkpoint inhibitor therapy is consistent with previous investigations supporting the importance of effector and regulatory T cells in the pathogenesis of these diseases.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.