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Considerations Regarding Mohs Surgery for Early-Stage Merkel Cell Carcinoma-Reply

Cheraghlou, Shayan; Carucci, John A
PMID: 38506790
ISSN: 2168-6084
CID: 5640552

Implementation of Mohs micrographic surgery at the VA New York Manhattan Harbor Healthcare System eliminated need for re-excision and decreased time to treatment: A retrospective and prospective cohort study

Himeles, Jaclyn Rosenthal; Steuer, Alexa Beth; Sally, Rachel; Gutierrez, Daniel; Zampella, John G; Stevenson, Mary L; Carucci, John A; Lee, Nayoung
PMID: 38149943
ISSN: 1097-6787
CID: 5623592

High-volume facilities are significantly more likely to use guideline-adherent systemic immunotherapy for metastatic Merkel cell carcinoma: implications for cancer care regionalization

Cheraghlou, Shayan; Pahalyants, Vartan; Jairath, Neil K; Doudican, Nicole A; Carucci, John A
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.
PMID: 38349538
ISSN: 1432-069x
CID: 5635292

Desmoplasia is associated with decreased cytotoxic and helper T cells and increased T cell exhaustion in cutaneous squamous cell carcinoma

Hirakawa, Yuka; Zhan, Qian; Essien, Sernah; Yu, Kenneth K; Murad, Fadi; Piris, Adriano; Ramsey, Matthew R; Schatton, Tobias; Carucci, John A; Schmults, Chrysalyne D
PMID: 38309575
ISSN: 1523-1747
CID: 5627062

Treatment of Merkel Cell Carcinoma With Mohs Micrographic Surgery Is Associated With Shorter Delays to Surgery in the United States

Cheraghlou, Shayan; Jairath, Neil K; Carucci, John A; Criscito, Maressa C
PMID: 37861352
ISSN: 1524-4725
CID: 5633012

The Novel Checkpoint Target Lymphocyte-Activation Gene 3 Is Highly Expressed in Cutaneous Squamous Cell Carcinoma

Dany, Mohammed; Doudican, Nicole; Carucci, John
BACKGROUND:Lymphocyte activation-gene 3 (LAG-3) is an emerging next-generation immune checkpoint molecule. We aim to define the expression pattern of LAG-3 in cutaneous squamous cell carcinoma (cSCC) as a first step to understand the role of LAG-3 in cSCC prognosis and therapy. OBJECTIVE:To define the expression pattern of LAG-3 in cSCC as a first step to understand the role of LAG-3 in cSCC prognosis and therapy. METHODS:To test whether LAG-3 is expressed on cSCC infiltrating lymphocytes, we isolated CD8 + T lymphocytes from three SCC tumors using flow cytometry and performed single-cell RNA sequencing for LAG-3 and programmed cell death protein -1 (PD-1). In addition, we evaluated LAG-3 mRNA expression in formalin-fixed, paraffin-embedded tissue using NanoString technology. RESULTS:Single-cell RNA sequencing showed that LAG-3 is expressed more than PD-1 in CD8 + tumor infiltrating lymphocytes (50.8% vs 35.2%, respectively). Quantifying LAG-3 mRNA expression showed that compared with normal skin, LAG-3 mRNA is approximately 8 fold higher in immunocompetent associated SCC tumors and approximately 2 fold higher in transplant associated SCC tumors ( p -values <.05). In addition, LAG-3 mRNA was expressed 7.2 fold higher in T2a SCC tumors compared with normal skin ( p -value <.05). CONCLUSION:Lymphocyte activation-gene 3 is expressed on SCC infiltrating T lymphocytes at a higher percentage than PD-1. In addition, LAG-3 mRNA expression is significantly higher in SCC tumors. Ongoing studies will be performed to define its role as an immune-related biomarker and as a therapeutic target.
PMID: 37962130
ISSN: 1524-4725
CID: 5611142

Reverse Cross Finger Flap for Deep Defects Involving the Dorsal Digits

Juarez, Michelle C; Criscito, Maressa C; Carucci, John A
PMID: 37788231
ISSN: 1524-4725
CID: 5590172

Evaluating Delays to Surgery for Melanomas Treated With Mohs Micrographic Surgery in the United States

Cheraghlou, Shayan; Criscito, Maressa C; Stevenson, Mary L; Carucci, John A
PMID: 37606888
ISSN: 1524-4725
CID: 5598382

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

Cheraghlou, Shayan; Doudican, Nicole A; Criscito, Maressa C; Stevenson, Mary L; Carucci, John A
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/CONCLUSIONS: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.
PMID: 37054818
ISSN: 1097-6787
CID: 5618742

Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma

Cheraghlou, Shayan; Doudican, Nicole A; Criscito, Maressa C; Stevenson, Mary L; Carucci, John A
IMPORTANCE:Merkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably. OBJECTIVE:To evaluate the association of surgical approach with overall survival after excision of localized T1/T2 MCC. DESIGN, SETTING, AND PARTICIPANTS:This retrospective cohort study used the National Cancer Database to assess adults with T1/T2 MCC who were diagnosed between January 1, 2004, and December 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities. Data analysis was performed from October 2022 to May 2023. EXPOSURE:Surgical approach. MAIN OUTCOMES AND MEASURES:Overall survival. RESULTS:A total of 2313 patients (mean [SD] age, 71 [10.6] years; 1340 [57.9%] male) were included in the study. Excision with MMS had the best unadjusted survival, with mean (SE) survival rates of 87.4% (3.4%) at 3 years, 84.5% (3.9%) at 5 years, and 81.8% (4.6%) at 10 years vs 86.1% (0.9%) at 3 years, 76.9% (1.2%) at 5 years, and 60.9% (2.0%) at 10 years for patients treated with WLE. Patients treated with narrow-margin excision had similar survival as those treated with WLE, with mean (SE) survival rates of 84.8% (1.4%) at 3 years, 78.3% (1.7%) at 5 years, and 60.8% (3.6%) at 10 years. On multivariable survival analysis, excision with MMS was associated with significantly improved survival compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04). High-volume MCC centers were significantly more likely to use MMS over WLE compared with other centers (odds ratio, 1.99; 95% CI, 1.63-2.44; P < .001). CONCLUSIONS AND RELEVANCE:In this cohort study, the use of MMS (compared with WLE) was associated with significantly improved survival for patients with localized MCC with pathologically confirmed negative lymph nodes treated with surgery. These data suggest that Mohs surgery may provide a more effective treatment for MCC primary tumors than conventional WLE, although the lack of randomization and potential for selection bias in this study highlight the need for future prospective work evaluating this issue.
PMID: 37610773
ISSN: 2168-6084
CID: 5598522