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Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated PTCH1, HEY2, LGR6, FZD2, LEF1, ALCAM, and RUNX1 expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.
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Importance: 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: To define standardized reporting measures for retrospective CSCC studies. Findings: 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: 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.
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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.
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Ahorro de Costo , Medicare , Cirugía de Mohs , Mejoramiento de la Calidad , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Medicare/economía , Estados Unidos , Mejoramiento de la Calidad/economía , Ahorro de Costo/estadística & datos numéricos , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/economía , Cirugía de Mohs/economía , Estudios de Seguimiento , Pautas de la Práctica en Medicina/economía , Pautas de la Práctica en Medicina/estadística & datos numéricos , Masculino , Femenino , Cirujanos/economía , Cirujanos/estadística & datos numéricos , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/economíaAsunto(s)
Carcinoma Basocelular , Neoplasias Cutáneas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Basocelular/patología , Carcinoma Basocelular/secundario , Estudios de Cohortes , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundarioRESUMEN
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.
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Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Carcinoma Basocelular/patología , Pronóstico , Ganglios Linfáticos/patología , Factores de Riesgo , PhiladelphiaRESUMEN
BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.
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Neoplasias Cutáneas , Cirujanos , Humanos , Neoplasias Cutáneas/cirugía , Cirugía de Mohs , Consenso , BenchmarkingRESUMEN
Importance: The 2022 National Comprehensive Cancer Network (NCCN) reclassified cutaneous squamous cell carcinoma (CSCC) into low-, high-, and very high-risk groups to better risk stratify tumors. Mohs micrographic surgery (Mohs) or peripheral and deep en face margin assessment (PDEMA) became preferred surgical modalities for high- and very high-risk tumors. This new risk stratification and the recommendation for Mohs or PDEMA in high- and very high-risk groups have not been validated. Objective: To compare outcomes in very high-, high-, and low-risk NCCN groups of CSCCs and in CSCCs treated with Mohs or PDEMA compared with wide local excision (WLE). Design, Setting, and Participants: This retrospective cohort study of CSCCs was performed in 2 tertiary care academic medical centers. Patients 18 years or older and diagnosed between January 1, 1996, and December 31, 2019, at Brigham and Women's Hospital and Cleveland Clinic Foundation were included. Data were analyzed from October 20, 2021, to March 29, 2023. Exposures: NCCN risk group, Mohs or PDEMA, and WLE. Main Outcomes and Measures: Local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). Results: A total of 10â¯196 tumors from 8727 patients were stratified by NCCN guidelines into low-, high-, and very high-risk groups (6003 [59.0%] men; mean [SD] age, 72.4 [11.8] years). Compared with the low-risk group, the high- and very high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio [SHR], 1.99 [95% CI, 1.21-3.27; P = .007]; very high-risk SHR, 12.66 [95% CI, 7.86-20.39; P < .001]), NM (high-risk SHR, 4.26 [95% CI, 1.28-14.23; P = .02]; very high-risk SHR, 62.98 [95% CI, 19.24-206.17; P < .001]), DM (high-risk SHR, 2.2 × 107 [95% CI, 4.7 × 103-1.1 × 1011; P < .001]; very high-risk SHR, 6.3 × 108 [95% CI, 1.4 × 105-2.9 × 1012; P < .001]), and DSD (high-risk SHR, 4.02 [95% CI, 1.18-13.71; P = .03]; very high-risk SHR, 93.87 [95% CI, 29.19-301.85; P < .001]). Adjusted 5-year cumulative incidence was significantly higher in very high- vs high- and low-risk groups for LR (9.4% [95% CI, 9.2%-14.0%] vs 1.5% [95% CI, 1.4%-2.1%] and 0.8% [95% CI, 0.5%-1.2%], respectively), NM (7.3% [95% CI, 6.8%-10.9%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.03%-0.3%], respectively), DM (3.9% [95% CI, 2.6%-5.6%] vs 0.1% [95% CI, 0.04%-0.2%] and 0.01% [95% CI, not applicable], respectively), and DSD (10.5% [95% CI, 10.3%-15.4%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.04%-0.3%], respectively). Compared with CSCCs treated with WLE, those treated with Mohs or PDEMA had lower risk of LR (SHR, 0.65 [95% CI, 0.46-0.90]; P = .009), DM (SHR, 0.38 [95% CI, 0.18-0.83]; P = .02), and DSD (SHR, 0.55 [95% CI, 0.36-0.84]; P = .006). Conclusions and Relevance: The findings of this cohort study suggest that the NCCN high- and very high-risk groups identify CSCCs at greatest risk for developing poor outcomes. Further, Mohs or PDEMA resulted in lower LR, DM, and DSD compared with WLE.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Factores de Riesgo , Medición de Riesgo , Recurrencia Local de Neoplasia/patología , Cirugía de Mohs/métodosRESUMEN
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.
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Satisfacción Personal , Cirujanos , Humanos , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Emociones , Encuestas y CuestionariosAsunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Estudios de Cohortes , Recurrencia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Although immunocompromised patients have a higher risk of developing cutaneous squamous cell carcinomas, it is unknown whether immune status is an independent risk factor for poor outcomes. OBJECTIVE: To compare cutaneous squamous cell carcinoma outcomes in immunocompromised and immunocompetent patients when controlling for T-stage. METHODS: We performed a retrospective cohort study at 2 tertiary care centers, examining 989 primary tumors from 814 immunocompromised patients (solid organ transplant: 259 [31.7%], chronic lymphocytic leukemia: 113 [13.9%]) and 6608 tumors from 4198 immunocompetent patients. Our primary outcome was the composite of disease-specific death or tumor metastasis ("poor outcomes"). RESULTS: Immunocompromised patients had 50% more high T-stage tumors (ie, Brigham and Women's Hospital stage T2b and T3), than immunocompetent patients (3.3% vs 4.9%, respectively; P < .001). Significant predictors of poor outcomes included tumor stage (sub hazards ratio [SHR], 14.8 for high T-stage tumors; 95% confidence interval [CI], 8.0-27.6; P < .001) and male sex (SHR, 2.3; 95% CI, 1.4-3.8; P = .002). Immune status was not a significant predictor (SHR, 1.04; 95% CI, 0.69-1.6; P = .85). LIMITATIONS: This study is retrospective. CONCLUSION: Although immunocompromised patients had 50% more high T-stage tumors than immunocompetent patients, immunocompromised patients had a similar chance of metastasis and disease-specific death when adjusting for T-stage in our cohort of primary tumors.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Estadificación de Neoplasias , Estudios de CohortesRESUMEN
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.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Márgenes de Escisión , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugíaRESUMEN
IMPORTANCE: Unlike Merkel cell carcinoma and melanoma, satellitosis or in-transit metastasis (S-ITM) is not incorporated into the current cutaneous squamous cell carcinoma (CSCC) staging systems. It is important to determine if the clinical outcomes of S-ITM are relevant to prognosis for patients with CSCC. OBJECTIVES: To evaluate the association of S-ITM with clinical outcomes in patients with CSCC and to determine its prognostic implications. DESIGN, SETTINGS, AND PARTICIPANTS: A dual-institution (Cleveland Clinic and Brigham and Women's Hospital) database was queried for patients who were treated for CSCC in 2010 to 2020. Patients who were node-negative and had S-ITM-the presence of dermal lesions between the primary tumor and first-echelon lymphatic nodal basins at any point in the disease course-were identified. Subcohorts of patients with T3N0 tumors, T4N0 tumors (bone invasive), N1 to 3, and M1 disease were identified for comparison. The American Joint Committee on Cancer staging system was used to define cancer stages. Data were analyzed from January 15 to March 31, 2021. MAIN OUTCOMES AND MEASURES: Pairwise comparison of CSCC recurrence and disease-specific survival in patients with and without S-ITM was performed using Cox proportional hazard modeling. Kaplan-Meier and Fine-Gray competing risk methods were used to estimate disease-specific survival and CSCC recurrence, respectively. RESULTS: In a total of 518 patients with CSCC, S-ITM was present in 72 (13.9 %) patients (median age [range], 73.9 [31.6-95.8] years; 59 [82%] men; 69 [96%] White non-Hispanic individuals; 25 [35%] patients with immunosuppression) who were node-negative. The subcohorts were composed of 341 patients with T3N0 cancer, 36 with T4N0, 70 with N1 to 3, and 19 with M1 disease. Pairwise comparisons between disease levels using Cox proportional hazard model demonstrated lower cumulative incidence of CSCC recurrence rates in the T3N0 (HR, 0.21; 95% CI, 0.14-0.30; P < .001) and T4N0 (HR, 0.36; 95% CI, 0.19-0.68; P = .001) cohorts compared with the S-ITM cohort. No significant difference was observed between patients who were node-positive and those with S-ITM (HR, 0.74; 95% CI, 0.48-1.14; P = .16). The 5-year disease-specific survival rates were 76% for T3N0, 64% for T4N0, 41% for S-ITM, and 39% for N1 to 3. Compared with the S-ITM cohort, DSS was significantly higher in the T3N0 (HR, 0.23; 95% CI, 0.15-0.35; P < .0001) and T4N0 (HR, 0.37; 95% CI, 0.19-0.76; P = .01) cohorts, and not significantly different in the node-positive (HR, 0.77; 95% CI, 0.84-3.93; P = .30) and metastatic cohorts (HR, 1.81; 95% CI, 0.84-3.93; P = .13). CONCLUSIONS AND RELEVANCE: This multi-institutional cohort study found that patients with CSCC and S-ITM appear to have clinical outcomes comparable to those of patients who are node-positive, and an increased risk of recurrence and worse survival compared with patients who have T3 and T4 disease. These outcomes are similar to those observed for Merkel cell carcinoma and melanoma. Given that S-ITM may be a powerful prognostic factor, it should be incorporated into clinical staging systems.
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Carcinoma de Células de Merkel , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutáneas , Anciano , Carcinoma de Células de Merkel/patología , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Melanoma/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
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.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
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.