Avelumab in the Treatment of Advanced Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Avelumab, a programmed death ligand-1 inhibitor, has shown success in providing durable responses for difficult-to-treat Merkel cell carcinomas (MCCs). OBJECTIVE: Evaluate the efficacy and safety of avelumab in the treatment of advanced MCC. METHODS: Studies reporting the use of avelumab as a monotherapy or in combination with other agents in the treatment of stage III or IV (advanced) MCC were included. The primary outcomes were overall response rate, overall survival (OS), and treatment-related adverse events. RESULTS: A total of 48 studies were included, involving 1,565 patients with advanced MCC. Most patients were male (1,051, 67.3%) with stage IV MCC (517, 97.0%). The overall response rate was 46.1% (partial response-25.4% and complete response-20.7%) after a mean follow-up period of 9.5 months. Kaplan-Meier survival curves for the pooled stage III and IV group demonstrated OS rates of 58% at 1 year, 47% at 2 years, and 28% at 5 years after completion of treatment with avelumab (median OS: 23.1 months). The most common treatment-related adverse events consisted of constitutional (44%), gastrointestinal (19%), and dermatologic (12%) symptoms. CONCLUSION: Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.

NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Family Planning Experiences and Challenges of Mohs Fellowship Trainees.

BACKGROUND: There is a paucity of literature describing family planning challenges faced by Mohs fellows. OBJECTIVE: To characterize perceptions about and experiences with family planning, fertility, lactation, and parental leave and identify ways to support parental health and family planning for Mohs fellows. MATERIALS AND METHODS: A voluntary, anonymous survey was distributed to Mohs surgeons who recently completed fellowship. RESULTS: In total, 116 Mohs surgeons completed the survey. Their mean age was 34.5 years old, and more were female ( n = 81, 69.8%) than male ( n = 35, 30.2%). Most had children before completion of their Mohs training ( n = 73, 62.9%). The most significant barrier to having children during fellowship was "loss of education or training time." Over 20% ( n = 23) of respondents or their partner had experienced infertility. Half of the 20 respondents ( n = 10) who breastfed or pumped did not have a convenient place to do so. CONCLUSION: This study elucidates trainee perceptions and gaps in parental support for Mohs fellowship trainees. In addition, barriers to implementing a universal family planning policy in Mohs surgery are discussed.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

Long-Term Appearance-Related Outcomes of Facial Reconstruction After Skin Cancer Resection.

Background: Aesthetic outcomes of facial reconstruction after skin cancer resection (RSCR) may affect long-term quality of life. Objective: To evaluate postoperative patient perceptions of skin cancer defect reconstruction using patient-reported outcome measures. Methods: Patients who underwent RSCR from 2016 to 2021 completed validated FACE-Q scales, including Satisfaction with Facial Appearance (SFA), Scar Appearance, and Appearance-Related Distress (ARD). Scores were scaled 0-100 and compared. Results: Sixty-one respondents completed the survey at a median of 3.0 (interquartile range: 1.6-4.1) years post-treatment. The majority had basal cell carcinomas (n = 41, 67%) and nasal defects (n = 40, 66%). Patients who received either revision surgery or office-based procedures to improve scarring reported lower satisfaction with scar appearance (65.8 ± 31.8 vs. 80.1 ± 20.8, p = 0.048). Dissatisfaction with scar appearance was correlated with decreased SFA (mean score: 76.6 ± 24.5; r = 0.44, p = 0.0004) and greater ARD (mean score: 23.8 ± 24.3; r = -0.66, p < 0.0001). Younger patients were also more likely to experience ARD (ß = -0.54, 95% confidence interval: [-0.96, -0.12, p = 0.014). SFA and ARD did not differ by operative factors, including reconstruction type, or single- versus multistage reconstruction. Conclusion: Although overall SFA after RSCR is high, regardless of reconstruction type, decreased satisfaction is correlated to poorer psychosocial function. Younger patients and those requiring revision procedures may be at greatest risk.

Self-supervised artificial intelligence predicts recurrence, metastasis and disease specific death from primary cutaneous squamous cell carcinoma at diagnosis.

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome (PO) including recurrence, metastasis and disease specific death (DSD) at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. In this multi-institutional study, we developed a state-of-the-art self-supervised deep-learning approach with interpretability power and demonstrated its ability to predict poor outcomes of cSCCs at the time of initial biopsy. By highlighting histomorphological phenotypes, our approach demonstrates that poor differentiation and deep invasion correlate with poor prognosis. Our approach is particularly efficient at defining poor outcome risk in Brigham and Women's Hospital (BWH) T2a and American Joint Committee on Cancer (AJCC) T2 cSCCs. This bridges a significant gap in our ability to assess risk among T2a/T2 cSCCs and may be useful in defining patients at highest risk of poor outcome at the time of diagnosis. Early identification of highest-risk patients could signal implementation of more stringent surveillance, rigorous diagnostic work up and identify patients who might best respond to early postoperative adjunctive treatment.

Skin Color Match in Head and Neck Reconstructive Surgery.

OBJECTIVES/HYPOTHESIS: To quantify the degree of color match achieved during microvascular facial reconstruction, and to describe a novel technique for improving reconstructive skin color match. We hypothesize that split-thickness skin grafts (STSG) placed atop de-epithelialized free tissue produces better facial skin color match than free tissue with intact epithelium. STUDY DESIGN: Cross sectional photographic study of reconstructed facial skin color match. METHODS: Sixty-eight adults, who underwent head and neck reconstructive surgery, were divided into six categories based on cutaneous reconstructive technique: cervicofacial flap, radial forearm free flap (RFFF), fibula free flap, anterolateral thigh free flap (ALT), STSG over adiopofascial flap (STAFF), and STSG over myogenous flap (STMF). Averaged color samplings of the reconstructed defect and adjacent normal skin were taken from digital photographs. The color difference was calculated using the delta-E calculation. Blinded expert observers also rated the degree of color match. Nonparametric cohort contrast and correlation statistical analyses were performed. RESULTS: The mean delta-E's and 10-point Likert ratings for the ALT, fibula, RFFF, STAFF, STMF, and cervicofacial flaps were 11.6, 10.0, 7.7, 6.3, 8.8, and 4.7, and 5.1, 6.4, 2.4, 3.2, 2.7, and 1.1, respectively. Likert scale inter-rater correlation was strong, with coefficient = 0.80. CONCLUSIONS: On average, STSG over de-epithelialized myogenous and adipofascial free tissue transfers produced a better color match than the skin paddles of donor sites, with the exception of the radial forearm donor site. Delta-E values obtained from photos correlated well with expert ratings of color match. This reliable technique for quantifying color match may be used in future studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1753-1759, 2022.

Should Sentinel Lymph Node Biopsy Status Guide Adjuvant Radiation Therapy in Patients With Merkel Cell Carcinoma?

PURPOSE: Radiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB). METHODS AND MATERIALS: Based on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded. RESULTS: Among 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P = .008), local recurrence-free survival (100% vs 76%, P = .009), and distant recurrence-free survival (100% vs 75%, P = .008), but not overall survival (87.5% vs 57.7%, P = .164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%). CONCLUSIONS: In this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Characterization of the 2019 Micrographic Surgery and Dermatologic Oncology Standardized Letter of Recommendation.

BACKGROUND: Traditional letters of recommendation used for postgraduate medical training applications have multiple limitations, including a lack of clarity, inflated and overly flattering assessments, and low reliability between interpreting faculty. A micrographic surgery and dermatologic oncology (MSDO) standardized letter of recommendation (SLOR) was created to improve the efficiency, validity, and stratification of applicants to dermatology fellowship training programs. OBJECTIVE: To analyze the MSDO SLOR for trends in grading based on letter-writer and applicant characteristics and to evaluate its ability to demonstrate differences between applicants. METHODS: Standardized letter of recommendations received by 4 fellowship programs from the 2019 San Francisco Match application cycle were reviewed retrospectively. RESULTS: Two hundred forty-nine SLORs were analyzed from 140 applicants. Grade inflation and limited variability in scores were evident. Higher scores correlated with the length of the relationships between letter-writers and applicants and with female letter-writer gender. There was no applicant gender or ethnicity bias detected. CONCLUSION: Despite score inflation, the MSDO SLOR allows for differentiation between fellowship applicants. Future studies are needed to further evaluate the reliability of the SLOR and find ways to improve its content.

Validation of the English Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) Questionnaire.

BACKGROUND: Keratinocyte carcinomas (KC) impact patient quality of life (QoL). There is a need for validated QoL instruments specific to KC. The Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire was developed to comprehensively measure issues of importance to patients with KC. OBJECTIVE: To validate and characterize the BaSQoL questionnaire for QoL measurement after diagnosis and treatment of KC. METHODS: This was a prospective, observational study. Patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were asked to fill out BaSQoL, Skin Cancer Index (SCI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Descriptive statistics and classical test theory were used to assess validity. RESULTS: One hundred eighty-seven subjects enrolled in this study: 122 with BCC and 65 with SCC. One hundred seventy-one subjects (91.4%) completed questionnaires at all 3 time points; 16 patients (8.6%) were lost to follow-up. Overall performance using classical test theory was good, with good internal consistency (Cronbach's α 0.63-0.80). BaSQoL subscales were strongly correlated with subscales of the SCI, demonstrating convergent validity, and weakly correlated with HADS, showing divergent validity. CONCLUSION: The English language version of BaSQoL has good face, content, and construct validity. This study validates BaSQoL for use in English-speaking patients with BCC and SCC.

A Review of the Use of Telemedicine in Dermatologic Surgery.

BACKGROUND: Telemedicine is an emerging field with numerous applications within medicine. Previous review articles describe its use within plastic surgery and otolaryngology but none, to the authors' knowledge, within dermatologic surgery. OBJECTIVE: To provide a review of the applications of telemedicine within dermatologic surgery. MATERIALS AND METHODS: A PubMed search of articles published on teledermatology was conducted in July 2018. Articles were selected based on their relevance to dermatologic surgery and reviewed for their discussion of the applications of telemedicine in surgical and cosmetic dermatology. RESULTS: The initial search resulted in 156 articles. Eleven ultimately met inclusion criteria: 2 in referral and consultation, 5 in telepathology, 2 in intraoperative uses, and 2 in postprocedural care. CONCLUSION: For preoperative consultation, teledermatology enables the surgeon to plan ahead and increases access to care by reducing the number of clinic visits. Telepathology has the potential to allow intraoperative consultation with a dermatopathologist to achieve accurate tumor clearance without delay. Smartglasses represent a promising technology for greater care coordination and a teaching tool. Postprocedural monitoring via text messaging provides convenient access to expert advice and early detection of postoperative complications. With increasing technologic advancements, telemedicine holds great potential to augment the dermatologic surgeon's daily practice.

Effect of Topical Brimonidine on Alcohol-Induced Flushing in Asian Individuals: A Randomized Clinical Trial.

Importance: Alcohol flushing syndrome (AFS, also known as Asian glow and Asian flush) affects 20% to 47% of East Asians and causes significant psychosocial distress. There are no approved treatments for this condition. Objective: To determine whether brimonidine gel, 0.33%, decreases facial erythema in patients with AFS after consumption of alcohol. Design, Setting, and Participants: In this randomized clinical trial, 20 healthy volunteers of East Asian descent with a self-reported history of AFS were recruited between April 2018 and March 2019. Interventions: Participants were randomized to application of brimonidine gel to either the left or right half of their face. Placebo control was applied to the opposite side. After 30 minutes, participants ingested alcohol. Main Outcomes and Measures: Outcomes were specified before data collection. The difference in erythema between the treated and placebo side of each participant's face was measured 60 minutes after drug application (primary outcome) and at 90 and 120 minutes after drug application (secondary outcomes). Participants were asked to rate their likelihood of using the medication again and their likelihood of recommending the medication to a friend on a scale of 0 to 10. Results: The mean (SD) age of the 20 individuals enrolled in the study was 30.5 (8.4) years, and there were 10 women (50%). There was a significant difference in erythema at 60 minutes after drug application as measured by the difference in Clinician Erythema Assessment score (2.1; 95% CI, 1.5-2.71; P < .001) and by the difference in Subject Self-Assessment score (1.7; 95% CI, 1.1- 2.3; P < .001). This effect persisted at 90 and 120 minutes. Individuals were likely to use the medication again (7.2; 95% CI, 6.0-8.3) and would also recommend it to a friend (7.6; 95% CI, 6.5-8.6). Conclusions and Relevance: This study demonstrates that brimonidine gel is effective in reducing the facial erythema of AFS. Patients with psychosocial distress due to AFS may benefit from treatment with brimonidine. Trial Registration: ClinicalTrials.gov identifier: NCT03497442.

Recent advances in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that has been historically associated with limited treatment options and poor prognosis. In the past 10 years, research in MCC has progressed significantly, demonstrating improved outcomes when treating with immunotherapy, particularly PD-1/PD-L1 inhibitors, when compared with conventional chemotherapy. There is also increasing evidence of the abscopal effect, a phenomenon describing the regression of untreated, distant MCC tumors following local radiation therapy. Additionally, antibodies to Merkel cell polyomavirus oncoproteins have been found to correlate with disease burden in a subset of patients, providing a useful tool for surveillance after treatment. Guidelines for the management of MCC will likely continue to change as research on surveillance and treatment of MCC continues.

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

IMPORTANCE: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients. OBJECTIVE: To develop recommendations for the care of adults with MAC. EVIDENCE REVIEW: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins. FINDINGS: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management. CONCLUSIONS AND RELEVANCE: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.