Faculty Bibliography

There is a paucity of information on racial and ethnic disparities relating to barriers to care in healthcare access and utilization in patients with cutaneous malignancies. We conducted a cross-sectional analysis of adults with melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) in the National Institutes of Health (NIH) All of Us Research Program collected between May 2018 and July 2022. Participants included adults (aged 18 or older) with cutaneous malignancy who completed the Health Care Access and Utilization survey. We identified 5,817 adults who were diagnosed with BCC (67%), cSCC (28.9%), and melanoma (23.9%). Non-Hispanic Black (NHB) and Hispanic patients were more likely than non-Hispanic White (NHW) patients to delay a primary care visit due to cost (p = 0.005 and p = 0.015, respectively). NHB patients were also more likely to delay care due to lack of transportation (p < 0.001). NHB and Hispanic patients were more likely to place importance on seeing a provider from the same background (NHB p < 0.002; Hispanic p = 0.002) and also were more likely to report never being able to see such a provider (NHB p < 0.001; Hispanic p = 0.002). Medicaid/Medicare patients, non-college graduates, and those with lower incomes also faced increased barriers to care, including delays due to cost and transportation issues. People of color with cutaneous malignancies are more likely to delay care in seeing primary care providers due to cost or transportation issues. This study provides important insights on disproportionate healthcare usage among racial/ethnic groups that may help mitigate healthcare disparities.

BACKGROUND:Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. OBJECTIVE:Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. MATERIALS AND METHODS/METHODS:Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. RESULTS:Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CONCLUSION/CONCLUSIONS:CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.

IMPORTANCE/UNASSIGNED:Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. OBJECTIVE/UNASSIGNED:To define standardized reporting measures for retrospective CSCC studies. FINDINGS/UNASSIGNED:An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.