The impact of facility characteristics on Merkel cell carcinoma outcomes: A retrospective cohort study.

BACKGROUND: Previous work has suggested that facility-level characteristics, such as case volume and academic affiliation, are associated with patient survival for rare malignancies. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with high mortality and rising incidence. The effect of facility characteristics on MCC outcomes is not yet established. OBJECTIVE: We aimed to investigate whether facility academic affiliation or case volume was associated with MCC patient survival. METHODS: We conducted a retrospective cohort analysis of US adult MCC cases diagnosed during 2004-2014 in the National Cancer Database. RESULTS: Both facility academic affiliation (P < .001) and case volume (P < .001) were significantly associated with patient survival. The 5-year survival of patients treated at academic facilities was 63.0% (standard error [SE] 1.7) and that of a propensity score- matched cohort of patients treated at nonacademic facilities was 53.4% (SE 1.9). The 5-year survival of patients treated at high-case volume facilities was 67.4% (SE 2.1) and that of a propensity score-matched cohort of patients treated at low- and intermediate-case volume facilities was 58.6% (SE 2.0). LIMITATIONS: Disease-specific survival and local recurrence data were not available. CONCLUSION: Treatment of MCC at academic and high-volume centers is associated with significantly improved patient survival. Further studies evaluating comorbidities and disease-specific survival are needed to establish whether experienced centers have improved outcomes in MCC treatment.

Defining and quantifying histopathologic risk factors for regional and distant metastases in a large cohort of vulvar squamous cell carcinomas.

BACKGROUND: Vulvar squamous cell carcinoma (vSCC) is a rare tumor with a good prognosis when treated at a localized stage. However, once regional/distant metastasis occurs, vSCC can be rapidly fatal. Thus, it is important to identify tumor prognostic features so that high-risk cases can be prioritized for further diagnostic workup and treatment. OBJECTIVE: To estimate the risk of regional/distant metastasis at presentation and sentinel lymph node status for vSCC based on histopathologic characteristics. METHODS: A retrospective cohort study of 15,188 adult vSCC cases from the National Cancer Database diagnosed from 2012 to 2019. RESULTS: We provide specific estimates of the risk of clinically positive nodes and metastatic disease at presentation and sentinel lymph node positivity according to tumor size, moderate/poor tumor differentiation, and lymph-vascular invasion. These histopathologic factors were all significantly associated with the tested clinical outcomes in a multivariable analysis. Moderate (hazard ratio, 1.190; P < .001) and poor differentiation (hazard ratio, 1.204; P < .001) and lymph-vascular invasion (hazard ratio, 1.465; P < .001) were also associated with significantly poorer overall survival. LIMITATIONS: Data on disease-specific survival not available in the data set. CONCLUSIONS: We demonstrate the association of the histopathologic characteristics of vSCC with clinically important outcomes. These data may provide individualized information when discussing diagnostic/treatment recommendations, particularly regarding sentinel lymph node biopsy. These data may also guide future staging and risk stratification efforts for vSCC.

Assessing Rates of Positive Surgical Margins After Standard Excision of Vulvar Melanomas.

BACKGROUND: Vulvar melanoma is a rare malignancy with frequent recurrence and poor prognosis. National guidelines recommend wide local excision of these tumors with allowances for narrower margins for anatomic and functional limitations, which are common on specialty sites. There is presently a lack of data of margin positivity after standard excision of vulvar melanomas. OBJECTIVE: We aim to evaluate the rate of positive margins after standard excision of vulvar melanomas. MATERIALS AND METHODS: Retrospective cohort study of surgically excised vulvar melanomas from the NCDB diagnosed from 2004 to 2019. RESULTS: We identified a total of 2,226 cases. Across surgical approaches and tumor stages, 17.2% (Standard Error [SE]: 0.8%) of cases had positive surgical margins. Among tumor stages, T4 tumors were most commonly excised with positive margins (22.9%, SE: 1.5%). On multivariable survival analysis, excision with positive margins was associated with significantly poorer survival (Hazard Ratio 1.299, p = .015). CONCLUSION: We find that positive margin rates after standard excision of vulvar malignancies are higher than for other specialty site melanomas. Our data suggest that use of surgical approaches with complete margin assessment may improve local control and functional outcomes for patients with vulvar melanoma as they have for patients with other specialty site melanomas.

Evaluating Rates of Positive Margins After Standard Excision of Cutaneous Adnexal Malignancies.

BACKGROUND: It is recommended to excise adnexal neoplasms with standard local excision or Mohs micrographic surgery (MMS), although many occur on high-risk sites such as the head and neck (H&N) and exhibit subclinical extension. Minimal evidence exists on the efficacy of standard excisions for these tumors. OBJECTIVE: To evaluate the rate of positive surgical margins after standard excision of adnexal tumors. METHODS: Retrospective cohort study of cutaneous adnexal malignancies from the National Cancer Database diagnosed from 2004 to 2019. RESULTS: The authors identified a total of 4,402 cases treated with standard excision. Tumors on the H&N were approximately twice as likely as those on the trunk and extremities (T&E) to be excised with positive margins (odds ratio 2.146, p < .001), with the highest estimated rate for eccrine adenocarcinoma (12.1%, SE: 2.3%). The subtype with the highest positive margin rate on the T&E was microcystic adnexal carcinoma (8.0%, SE: 2.9). Positive margins were associated with poorer overall survival on multivariable survival analysis (hazard ratio 1.299, p = .015). CONCLUSION: The authors present subtype- and site-specific positive margin rates for adnexal tumors treated with standard excision, which suggest that tumors on the H&N and some T&E subtypes, should be considered for MMS.

Trends in the Cost and Utilization of Omalizumab in the Medicare Population: 2013-2017.

Background: Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has shown that access to injectable biologics varies across US counties. In the present study we evaluate geographic and temporal trends in the utilization of omalizumab in the Medicare population by dermatologists, with its use by allergists and pulmonologists as comparators. Methods: We analyzed year-over-year trends in omalizumab utilization across geographic regions using the Medicare Provider Utilization and Payment Data: Part D files. Results: Utilization of omalizumab by dermatologists increased rapidly after its FDA approval, from 0.08 claims/100,000 enrollees totaling $209/100,000 enrollees in 2014 to 1.45 claims/100,000 enrollees totaling $3115/100,000 enrollees in 2017. Nonetheless, prescribing dermatologists were present in only 2.8% (95% Confidence Interval (CI): 2.0%-3.9%) and 0.2% (95% CI: 0.0%-0.5%) of metropolitan and non-metropolitan counties, respectively, in 2017, demonstrating limited availability, especially in non-metropolitan counties. Similarly, prescribers of any specialty were available in 32.9% (95% CI: 30.2%-35.6%) and 3.8% (95% CI: 3.1%-4.8%) of metropolitan and non-metropolitan counties, respectively, in 2017. Conclusions: Our data suggest that despite increasing omalizumab utilization, there remains a lack of access across many counties, particularly in non-metropolitan regions. Efforts to expand omalizumab prescriber accessibility in these counties may improve outcomes for patients with CSU.

Utilization, cost, and provider trends in patch testing among Medicare beneficiaries in the United States from 2012 to 2017.

BACKGROUND: Patch testing is the best diagnostic test for allergic contact dermatitis. However, there is presently a lack of data on the test's geographic availability and the characteristics of the providers offering this test across the United States. OBJECTIVE: To evaluate the geographic variation in the availability of patch testing for the Medicare population and to characterize the temporal trends of patch testing cost, use, and provider specialty from 2012 to 2017. METHODS: Retrospective cohort study of the Medicare Provider Utilization and Payment Data from 2012 to 2017. RESULTS: As of 2017, patch testing was available in 20.3% of metropolitan counties and in 1.1% of nonmetropolitan counties. From 2012 to 2017 in metropolitan regions, the number of beneficiaries tested by dermatologists grew by an average annual growth rate of 1.84%, whereas those tested by allergists grew by an average annual growth rate of 20.31%. Most providers that averaged use of 80 or more patches per beneficiary were dermatologists (76.3%). LIMITATIONS: Analysis was restricted to Medicare Part B claims; data were unavailable on individuals with commercial insurance. CONCLUSIONS: Most of the increase in patch testing utilization from 2012 to 2017 has been in metropolitan regions. Although growth was especially prominent among allergists in metropolitan counties, the majority of providers performing comprehensive patch testing were dermatologists.

Trends in office visits and treatment for urticaria in children in the United States, 1998-2016.

BACKGROUND/OBJECTIVES: Urticaria is a common condition with an estimated prevalence of up to 23% in the pediatric population. Studies characterizing visits and treatments for urticaria in the pediatric population are unavailable. Understanding visit and treatment trends for urticaria in the pediatric population may help inform care for patients with urticaria. METHODS: A total of 108 278 outpatient records from the National Ambulatory Medical Care Survey representing 3.4 billion visits by patients of age 18 and younger were analyzed. This study included the calendar years 1998 through 2016. RESULTS: Pediatricians saw the largest proportion of all visits (52.7%). Male and female patients accounted for approximately equal proportions of all visits for urticaria. There was a slight male predominance in visits to pediatricians (53.7%), whereas dermatologists saw female patients more frequently (63.3%). Most visits for urticaria were by non-Hispanic (78.1%) and White (78.2%) patients. H1 antihistamines were the most commonly prescribed treatment (70.3%), whereas topical corticosteroids were prescribed least frequently (4.9%). Topical corticosteroids were most frequently prescribed by dermatologists (7.7%). Non-H1 antihistamine and non-corticosteroid therapy were prescribed in 9.7% of all visits and in 4.5% of visits to pediatricians. Most visits for urticaria were to physicians in metropolitan areas (88.8%). Pediatricians saw the highest number of non-metropolitan area visits (56.3%). CONCLUSIONS: H1 antihistamines were the most commonly used therapy (70%), consistent with established treatment guidelines. Male and female pediatric patients present equally often for urticaria, but sex differences were seen with visit frequencies to certain specialties.

A machine-learning modified CART algorithm informs Merkel cell carcinoma prognosis.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with a high mortality rate. MCC staging is currently based on tumour primary size, clinical detectability of lymph node metastases, performance of a lymph node biopsy, and presence of distant metastases. OBJECTIVE: We aimed to use a modified classification and regression tree (CART) algorithm using available data points in the National Cancer Database (NCDB) to elucidate novel prognostic factors for MCC. METHODS: Retrospective cohort study of the NCDB and Surveillance, Epidemiology, and End Results (SEER) registries. Cases from the NCDB were randomly assigned to either the training or validation cohorts. A modified CART algorithm was created with data from the training cohort and used to identify prognostic groups that were validated in the NCDB validation and SEER cohorts. RESULTS: A modified CART algorithm using tumour variables available in the NCDB identified prognostic strata as follows: I: local disease, II: ≤3 positive nodes, III: ≥4 positive nodes, and IV: presence of distant metastases. Three-year survival for these groups in the NCDB validation cohort were 81.2% (SE: 1.7), 59.6% (SE: 3.0), 38.0% (SE: 6.0), and 20.2% (SE: 7.0), respectively. These strata were exhibited greater within-group homogeneity than AJCC groups and were more predictive of survival. CONCLUSIONS: Risk-stratified grouping of MCC patients incorporating positive lymph node count were strongly predictive of survival and demonstrated a high degree of within-group homogeneity and survival prediction. Incorporation of positive lymph node count within overall staging or sub-staging may help to improve future MCC staging criteria.

Mutations in KRT10 in epidermolytic acanthoma.

BACKGROUND: Epidermolytic acanthoma (EA) is a rare acquired lesion demonstrating a characteristic histopathological pattern of epidermal degeneration referred to as epidermolytic hyperkeratosis (EHK). On histopathological analysis, EA appears nearly identical to inherited EHK-associated dermatoses such as epidermolytic ichthyosis and ichthyosis bullosa of Siemens. While it has been speculated that EA is caused by mutations in KRT10, KRT1, or KRT2 found in these inherited dermatoses, none have yet been identified. Herein, we aim to identify the contributions of keratin mutations to EA. METHODS: Using genomic DNA extracted from paraffin-embedded samples from departmental archives, we evaluated a discovery cohort using whole-exome sequencing (WES) and assessed remaining samples using Sanger sequencing screening and restriction fragment length polymorphism (RFLP) analysis. RESULTS: DNA from 16/20 cases in our sample was of sufficient quality for polymerase chain reaction amplification. WES of genomic DNA from lesional tissue revealed KRT10 c.466C > T, p.Arg156Cys mutations in 2/3 samples submitted for examination. RFLP analysis of these samples as well as eight additional samples confirmed the mutations identified via WES and identified four additional cases with Arg156 mutations. In sum, 6/11 screened cases showed hotspot mutation in KRT10. CONCLUSIONS: Hotspot mutations in the Arg156 position of KRT10, known to cause epidermolytic ichthyosis, also underlie EA.

Early Adoption of Dupilumab in the Medicare Population in 2017.

Background: In March of 2017, dupilumab became the first FDA approved injectable biologic for treatment of moderate-to-severe atopic dermatitis (AD). As the first drug in this class for AD, dupilumab has revolutionized the disease's treatment and improved patient outcomes significantly. Previous work has demonstrated that dermatologic injectable biologics are not uniformly accessible to patients in the US, and that patients in more rural regions are less likely to have access to these medications. In this study, we aimed to evaluate the early utilization trends of dupilumab for the Medicare population in the first year of its FDA approval (2017). Methods: Retrospective cohort study of the Medicare Provider Utilization and Payment Data. Counties were categorized by Rural-Urban Continuum Codes (RUCC) based on size, extent of urbanization, and proximity to a metropolitan (metro) area as defined by the National Center for Health Statistics Urban-Rural Classification Scheme for Counties. Results: There were 142 individuals who prescribed dupilumab at least 10 times in 2017, 80% of whom were dermatologists. Of these providers, 130 (91.5%) practiced in metropolitan (metro) counties and 12 practiced in non-metro counties. There were 14 cities with two or more dupilumab prescribers, with highest numbers observed in New York, NY (8 providers); Philadelphia, PA (6 providers); Phoenix, AZ (5 providers); and Norfolk, VA (4 providers). Conclusions: There are differences in access to dupilumab in the Medicare population based on geographic location in the US. Trends of decreased access to novel dermatologic biologics in rural areas of the US may begin at their introduction to the market, identifying a potential target for future interventions to equalize access.

Treatment of primary nonmetastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival.

BACKGROUND: Previous studies of cancer care have demonstrated improved long-term patient outcomes for those treated at high-volume centers. The influence of treatment center characteristics on outcomes for primary nonmetastatic melanoma is not currently established. OBJECTIVE: We aimed to investigate the association of cancer treatment center case volume and academic affiliation with long-term patient survival for cases of primary nonmetastatic melanoma. METHODS: Cases of melanoma diagnosed in US adults from 2004 to 2014 and included in the National Cancer Database were identified. Hospitals were grouped by yearly case-volume quartile: bottom quartile, 2 middle quartiles, and top quartile. RESULTS: Facility case volume was significantly associated with long-term patient survival (P < .0001). The 5-year survival rates were 76.8%, 81.9%, and 86.4% for patients treated at institutions in the bottom, middle, and top quartiles of case volume, respectively. On multivariate analysis, treatment at centers in both middle quartiles (hazard ratio, 0.834; 95% confidence interval, 0.778-0.895) and in the top quartile (hazard ratio, 0.691; 95% confidence interval, 0.644-0.741) of case volume was associated with improved survival relative to that of patients treated at hospitals in the bottom quartile of case volume. Academic affiliation was associated with improved outcomes for top-quartile- but not middle-quartile-volume facilities. LIMITATIONS: Disease-specific survival was not available. CONCLUSIONS: Treatment at a high-volume facility is associated with improved long-term patient survival for melanoma. High-volume academic centers have improved patient outcomes compared with other high-volume centers.

Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.

BACKGROUND: The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. METHODS: A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. RESULTS: For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. CONCLUSIONS: Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in this group. Cancer 2018;124:717-26. © 2017 American Cancer Society.