A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis. OBJECTIVE: To assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis. METHODS: Retrospective cohort study of 53 patients with mBCC treated at 4 large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 and December 31, 2021. RESULTS: A total of 53 patients with mBCC were identified across 4 centers, 22 (42%) of whom had mBCC with spread limited to lymph nodes and 31 (58%) patients with distant organ spread (with or without lymph node involvement). Overall, half (n = 11) of patients with nodal metastasis achieved complete remission of disease, compared with just 1 (3%) patient with distant metastasis. The 5-year survival for nodal and distant metastatic patients was 89.3% and 61.0%, respectively. LIMITATIONS: Small sample size due to disease rarity. CONCLUSIONS AND RELEVANCE: Patients with nodal disease are more likely to have disease remission whereas patients with distant metastasis are more likely to have persistent disease and die from their disease. However, 5-year survival rates exceed 50%, even for stage IV disease.

Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile.

Aim: To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART).Materials & methods: Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event.Results: Random sampling of matched patient pairs (n = 52 ART-treated; 371 no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1.Conclusion: The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1).

Independent validation study: 40-GEP identifies patients with cutaneous squamous cell carcinoma who would be most likely to benefit from adjuvant radiation therapy.

5-Year Follow-Up of a Physician Performance Feedback Report Intervention to Reduce Overuse and Excess Cost: A National Cohort Study.

BACKGROUND: Mohs micrographic surgery efficiently treats skin cancer through staged resection, but surgeons' varying resection rates may lead to higher medical costs. OBJECTIVE: To evaluate the cost savings associated with a quality improvement. MATERIALS AND METHODS: The authors conducted a retrospective cohort study using 100% Medicare fee-for-service claims data to identify the change of mean stages per case for head/neck (HN) and trunk/extremity (TE) lesions before and after the quality improvement intervention from 2016 to 2021. They evaluated surgeon-level change in mean stages per case between the intervention and control groups, as well as the cost savings to Medicare over the same time period. RESULTS: A total of 2,014 surgeons performed Mohs procedures on HN lesions. Among outlier surgeons who were notified, 31 surgeons (94%) for HN and 24 surgeons (89%) for TE reduced their mean stages per case with a median reduction of 0.16 and 0.21 stages, respectively. Reductions were also observed among outlier surgeons who were not notified, reducing their mean stages per case by 0.1 and 0.15 stages, respectively. The associated total 5-year savings after the intervention was 92 million USD. CONCLUSION: The implementation of this physician-led benchmarking model was associated with broad reductions of physician utilization and significant cost savings.

Well-Being and Professional Fulfillment in Mohs Surgeons: An Explanatory Sequential Mixed-Method Design Study.

BACKGROUND: There are limited data evaluating specific themes of well-being and professional fulfillment in Mohs surgeons. OBJECTIVE: To identify factors that drive occupational distress and those that promote well-being and professional fulfillment among Mohs surgeons. METHODS: This is an explanatory sequential mixed-method study, using semistructured individual interviews. Common drivers of physician well-being and fulfillment were identified based on the independent assessment of the coding in the interview transcripts. RESULTS: This study reports the following qualitative themes: (1) gratitude for the chosen profession and relationships, (2) unrealistic standards of perfection that may have contributed to past career success but are unattainable and create emotional burden, and (3) ability to practice in a manner aligned with personal values promotes professional fulfillment. CONCLUSION: This study suggests that gratitude, self-compassion, and ability to practice in a manner aligned with personal values promote well-being and professional fulfillment in Mohs surgeons. Notably, we found that unrealistic standards of perfection and personal-organization practice incongruences contribute to burnout.

Identifying Brigham and Women's Hospital stage T2a cutaneous squamous cell carcinomas at risk of poor outcomes.

BACKGROUND: Although most of the poor outcomes with cutaneous squamous cell carcinoma (CSCC) occur in high-stage tumors, 26% of nodal metastases and 8% of disease-specific deaths develop in Brigham and Women's Hospital (BWH) T2a tumors. OBJECTIVE: To determine risk factors associated with poor outcomes (nodal metastasis, distant metastases, and disease-specific deaths) in BWH T2a CSCC. METHODS: A 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes. RESULTS: Presence of 1 major criterion (primary tumor diameter ≥40 mm, invasion depth beyond subcutaneous fat, poor differentiation, or large-caliber perineural invasion) and ≥ 1 minor criterion (invasion depth in subcutaneous fat, moderate differentiation, small-caliber perineural invasion, or lymphovascular invasion) was most predictive of developing poor outcomes (area under the curve, 0.53; C-statistic, 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The 5-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI, 5.1-13.7) compared to 2.8% (95% CI, 1.9-4.1) in other T2a tumors (sub-hazard ratio, 3.0; 95% CI, 1.5-5.8). LIMITATIONS: Multi-institutional cohort study was not externally validated. CONCLUSIONS: BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.

Higher metastasis and death rates in cutaneous squamous cell carcinomas with lymphovascular invasion.

BACKGROUND: Lymphovascular invasion (LVI) is an aggressive histologic finding but is excluded from current staging systems due to its lack of demonstrated independent prognostic significance. OBJECTIVE: To evaluate the impact of LVI on cutaneous squamous cell carcinoma tumor outcomes. METHODS: In total, 10,707 cutaneous squamous cell carcinoma tumors from a 20-year, retrospective, multicenter cohort were stratified by the presence (LVI+) or absence (LVI-) of LVI. Outcomes (local recurrence, in-transit metastasis, nodal metastasis, disease-specific death) were compared based on low (Brigham and Women's Hospital [BWH] stage T1/T2a) and high (BWH T2b/T3) tumor stages. RESULTS: Of the 10,707 tumors, 78 had LVI. The analysis of low-stage BWH tumors showed the LVI+ group had a significantly higher 5-year cumulative incidence of local recurrence (LVI+: 12.3%; LVI-: 1.1%; P < .01), metastasis (LVI+: 4.2%; LVI-: 0.4%; P < .01), and disease-specific death (LVI+: 16.2%; LVI-: 0.4%; P < .01). The analysis of BWH high-stage tumors showed the LVI+ group maintained a higher 5-year cumulative incidence of metastasis (LVI+: 28.5%; LVI-: 16.8%; P = .06) and disease-specific death (LVI+: 25.3%; LVI-: 13.9%; P = .03), however, there was no difference in local recurrence (LVI+: 16.3%; LVI-: 15.8%; P = .11). LIMITATIONS: Retrospective study design. CONCLUSION: LVI+ cutaneous squamous cell carcinomas have higher rates of metastasis and death at 5 years. Future staging systems should consider incorporating LVI.

Adjuvant radiation following clear margin resection of high T-stage cutaneous squamous cell carcinoma halves the risk of local and locoregional recurrence: A dual-center retrospective study.

BACKGROUND: Although adjuvant radiation (ART) following clear margin surgery is recommended for select high-risk cutaneous squamous cell carcinomas, efficacy data are limited. OBJECTIVE: To evaluate the impact of ART on outcomes following clear margin surgery for high T-stage cutaneous squamous cell carcinomas. METHODS: A 20-year retrospective cohort study at 2 academic centers of high T-stage cutaneous squamous cell carcinomas (Brigham and Women's Hospital T2b or T3) with negative histologic margins post resection. Local recurrence (LR) and locoregional recurrence (LRR) were compared by whether tumors received ART or observation. RESULTS: A total of 508 tumors were included, of which 96 underwent ART (ART+). ART+ had a lower 5-year cumulative incidence of LR (ART+, 3.6% [95% CI, 1.6%-7.7%] vs ART-, 8.7% [95% CI, 6.3%-12.0%]) and LRR (ART+, 7.5% [95% CI, 4.4%-11.9%] vs ART-, 15.3% [95% CI, 11.9%-22.1%]). Recurrent tumors ≥6 cm or Brigham and Women's Hospital T3 tumors were classified as high-risk due to a higher 5-year cumulative incidence of LRR (High-risk, 26.3% [95% CI, 19.0%-35.7%]). High-risk tumors treated with ART had a lower 5-year cumulative incidence of LRR (ART+, 17.2% [95% CI, 11.9%-26.4%] vs ART-, 31.0% [95% CI, 26.1%-40.8%]). LIMITATIONS: Retrospective design, heterogeneous population, variations in radiation protocols. CONCLUSION: ART following clear margin surgery for high T-stage cutaneous squamous cell carcinomas resulted in half the risk of LR and LRR.

Risk factors and timing of subsequent cutaneous squamous cell carcinoma in patients with cutaneous squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: Information about the frequency and timing of subsequent cutaneous squamous cell carcinoma (cSCC), along with associated risk factors, is limited. However, this information is crucial to guide follow-up care for these patients. OBJECTIVE: To evaluate the risk and timing of subsequent cSCC in patients who presented with an initial diagnosis of cSCC. METHODS: Retrospective review of an institutional review board-approved, single-institution registry of invasive cSCC. All patients had at least 2 primary cSCCs diagnosed on 2 separate dates 2 months apart. RESULTS: A total of 299 primary cSCCs were included. At 6 months from initial cSCC diagnosis, 18.06% (n = 54) of patients developed subsequent cSCC; at 1 year, 31.77% (n = 94); at 3 years, 67.56% (n = 202); and at 5 years, 87.96% (n = 263) developed subsequent cSCC. Risk factors associated with subsequent cSCC include age at initial diagnosis (hazard ratio [HR], 1.02; 95% confidence interval, 1.004-1.027; P = .008), T2 stage (HR, 1.66; 95% CI, 1.07-2.57; P = .025), and poor tumor grade. Tumor grades well, moderate, and unknown have HRs of 0.21 (P < .001), 0.16 (P .001), and 0.25 (P = .001), respectively. CONCLUSIONS: Of patients who develop subsequent cSCC, 18.06% do so within 6 months, and 31.77% do so within 1 year of initial cSCC diagnosis. Patients with advanced age, poor histologic differentiation, and American Joint Committee on Cancer T2 stage are at highest risk. Close clinical follow-up after the initial diagnosis is recommended.

Outcomes in intermediate-risk squamous cell carcinomas treated with Mohs micrographic surgery compared with wide local excision.

BACKGROUND: Brigham and Women's Hospital stage T2a squamous cell carcinomas, demonstrating a single high-risk feature, have a low risk of metastasis and death but an increased risk of local recurrence. Little evidence exists for the best treatment modality and associated outcomes in T2a squamous cell carcinoma. OBJECTIVE: We aimed to compare outcomes for T2a squamous cell carcinoma treated by Mohs micrographic surgery compared with wide local excision with permanent sections. METHODS: Retrospective review of an institutional review board-approved single-institution registry of T2a squamous cell carcinoma. RESULTS: Three hundred sixty-six primary T2a tumors were identified, including 240 squamous cell carcinomas (65.6%) treated with Mohs micrographic surgery and 126 (34.4%) treated with wide local excision. A total of 32.5% of patients were immunosuppressed and mean oncologic follow-up was 2.8 years. Local recurrence was significantly more likely after wide local excision (4.0%) than after Mohs micrographic surgery (1.2%) (P = .03). Multiple logistic regression demonstrated immunocompromised state (odds ratio [OR] 5.1; 95% confidence interval [CI] 1.1-23.3; P = .03) and wide local excision (OR 4.8; 95% CI 1.1-21.6; P = .04) associated with local recurrence; and wide local excision (OR 7.8; 95% CI 2.4-25.4; P < .001), high-risk head and neck location (OR 8.3; 95% CI 1.8-38.7; P = .004), and poor histologic differentiation (OR 4.7; 95% CI 1.4-15.4; P = .03) associated with poor outcomes (overall recurrence or disease-specific death). CONCLUSION: Mohs micrographic surgery provides improved outcomes in Brigham and Women's Hospital T2a squamous cell carcinoma.

A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN). This is the largest multi-institutional study to date investigating the effect of immune status on disease outcomes in patients with cSCC-HN who underwent surgery and received postoperative radiation therapy (RT). METHODS: Patients from 3 institutions who underwent surgery and also received postoperative RT for primary or recurrent, stage I through IV cSCC-HN between 1995 and 2015 were included in this institutional review board-approved study. Patients categorized as immunosuppressed had chronic hematologic malignancy, human immunodeficiency/acquired immunodeficiency syndrome, or had received immunosuppressive therapy for organ transplantation ≥6 months before diagnosis. Overall survival, locoregional recurrence-free survival, and progression-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazards regression. RESULTS: Of 205 patients, 138 (67.3%) were immunocompetent, and 67 (32.7%) were immunosuppressed. Locoregional recurrence-free survival (47.3% vs 86.1%; P < .0001) and progression-free survival (38.7% vs 71.6%; P = .002) were significantly lower in immunosuppressed patients at 2 years. The 2-year OS rate in immunosuppressed patients demonstrated a similar trend (60.9% vs 78.1%; P = .135) but did not meet significance. On multivariate analysis, immunosuppressed status (hazard ratio [HR], 3.79; P < .0001), recurrent disease (HR, 2.67; P = .001), poor differentiation (HR, 2.08; P = .006), and perineural invasion (HR, 2.05; P = .009) were significantly associated with locoregional recurrence. CONCLUSIONS: Immunosuppressed patients with cSCC-HN had dramatically lower outcomes compared with immunocompetent patients, despite receiving bimodality therapy. Immune status is a strong prognostic factor that should be accounted for in prognostic systems, treatment algorithms, and clinical trial design. Cancer 2017;123:2054-2060. © 2017 American Cancer Society.

Managing sharps injuries and other occupational exposures to HIV, HBV, and HCV in the dermatology office.

Dermatologists and their staff are at risk for needlestick injuries and exposures to body fluids. Despite the availability of treatment to reduce the risk of blood-borne infection, many exposures go unreported. This paper identifies current recommendations and the specific details for response to occupational exposures to HIV, hepatitis B virus, and hepatitis C virus in the dermatology office. Issues surrounding each virus are discussed individually, and a summary step-by-step algorithm of how to proceed in the event of an occupational exposure is presented. In addition, a focused Practice Improvement Activity that is based on this paper and provides Maintenance of Certification credit has been developed. To view and participate, visit https://secure.dataharborsolutions.com/abdermorg/.

Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study.

BACKGROUND/OBJECTIVES: The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective ß1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial. METHODS: Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS). RESULTS: The mean change in HAS was -2.94 ± 1.20 for patients treated with atenolol and -2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol. CONCLUSION: Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.

Periocular Skin Cancer in Solid Organ Transplant Recipients.

PURPOSE: To determine the proportion of solid organ transplant recipients developing periocular nonmelanoma skin cancer and to describe the morbidity of these cancers in transplant recipients. DESIGN: Cohort study. PARTICIPANTS: Consecutive patients undergoing solid organ transplantation at the Cleveland Clinic between 1990 and 2008. METHODS: The charts of all patients receiving a solid organ transplant from 1990-2008 evaluated in the dermatology department for a subsequent biopsy-proven head and neck malignancy through April 2015 were reviewed. Patients with a periocular region nonmelanoma skin cancer (NMSC) or a nonperiocular NMSC causing a complication requiring eyelid surgery were included. Charts were reviewed for demographic data; transplant date, type, and source; immunosuppressive agents received at diagnosis; and type of NMSC, number of nonperiocular NMSCs, ophthalmologic findings, and periocular sequelae after the repair. MAIN OUTCOME MEASURES: Primary outcome measures included the type, location, final defect size, tumor-node-metastasis classification, presence of perineural invasion, and reconstruction technique(s) used for each periocular NMSC. Secondary outcome measures included the type and treatment of ocular sequelae due to nonperiocular facial NMSC. RESULTS: A total of 3489 patients underwent solid organ transplantation between 1990 and 2008. Of these, 420 patients were evaluated in the dermatology clinic for biopsy-proven NMSC of the head and neck during the study period, and 11 patients (15 malignancies) met inclusion criteria. Nine patients developed 12 periocular malignancies and 3 patients required eyelid surgery for facial malignancies outside the periocular zone. All 11 patients developed a squamous cell carcinoma (14 malignancies), and 1 patient (1 malignancy) also developed a periocular basal cell carcinoma. There was orbital invasion in 4 cases and paranasal and/or cavernous sinus invasion in 3 cases. Two patients underwent exenteration. Seven cases required reconstruction with a free flap or graft. Periocular sequelae included lower eyelid ectropion (6 malignancies), dry eye and/or exposure symptoms (8 malignancies), unilateral vision loss (3 malignancies), and facial nerve paresis (5 malignancies). CONCLUSIONS: Squamous cell carcinoma affecting the periocular region represents a risk of solid organ transplantation and may produce significant ocular morbidity, including the need for major eyelid reconstruction, globe loss, and disfiguring surgery.