Publications by authors named "Michael R Migden"

51 Publications

Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma.

JID Innov 2021 Dec 25;1(4):100045. Epub 2021 Aug 25.

Arkansas Dermatology & Skin Cancer Center, Little Rock, Arkansas, USA.

Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review. Consensus was achieved through modified Delphi methodology. The steering committee included five dermatologists, three medical oncologists, two head and neck surgeons, one radiation oncologist, and a patient advocacy group representative. The steering committee aligned on the following clinical topics: diagnosis and identification of patients considered not candidates for surgery; staging systems and risk stratification in cutaneous squamous cell carcinoma; the role of radiation therapy, surgery, and systemic therapy in the management of advanced disease, with a focus on immunotherapy; referral patterns; survivorship care; and inclusion of the patient's perspective. Consensus was achieved on 34 recommendations addressing 12 key clinical questions. The Expert Cutaneous Squamous Cell Carcinoma Leadership steering committee's evidence-based consensus recommendations may provide healthcare professionals with practically oriented guidance to help optimize outcomes for patients with advanced cutaneous squamous cell carcinoma.
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http://dx.doi.org/10.1016/j.xjidi.2021.100045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659794PMC
December 2021

Immunotherapy and Systemic Treatment of Cutaneous Squamous Cell Carcinoma.

Dermatol Pract Concept 2021 Nov 1;11(Suppl 2):e2021169S. Epub 2021 Oct 1.

Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Cutaneous squamous cell carcinomas (cSCC) represent one of the most diagnosed non-melanoma skin cancers and its incidence is increasing globally. Whereas early stage and low risk cSCC is typically treated with surgery, and in some cases other localized therapeutic modalities, locally advanced or metastatic cSCC is a cause of significant morbidity and mortality that requires a different approach to therapy. Therapeutic attempts at treating advanced cSCC include a multi-disciplinary approach with considerations for surgery, radiation, and systemic therapies. In this review, we will discuss the various systemic therapies that have been trialed for advanced cSCC, beginning with the early cytotoxic and platinum-based agents as well as their corresponding limitations. We will then review the targeted approaches using EGFR inhibitors prior to discussing the more recent immunotherapeutics that have shown good tumor responses in this often-lethal disease.
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http://dx.doi.org/10.5826/dpc.11S2a169SDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609954PMC
November 2021

Use of PD-1 Inhibitors in the Treatment of Advanced Basal Cell Carcinoma.

Dermatol Surg 2021 11;47(11):1511-1512

Departments of Dermatology and Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1097/DSS.0000000000003207DOI Listing
November 2021

Treatment of advanced cutaneous squamous cell carcinoma: a Mohs surgery and dermatologic oncology perspective.

Future Oncol 2021 Dec 5;17(35):4971-4982. Epub 2021 Oct 5.

Departments of Dermatology & Head & Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Locally advanced or metastatic cutaneous squamous cell carcinoma no longer amenable to surgical resection or primary radiation therapy requires an alternative approach to treatment. Until 2018, management consisted of limited systemic chemotherapies, which carried marginal clinical benefit. The introduction of immunotherapy with anti-PD-1 antibodies resulted in alternative treatment options for advanced cutaneous squamous cell carcinoma with substantial antitumor activity, durable response and acceptable safety profile. The field of immunotherapeutics continues to expand with adjuvant, neoadjuvant and intralesional studies currently in progress. Herein, the authors discuss their approach for the treatment of advanced cutaneous squamous cell carcinoma from the perspective of a Mohs surgeon and a dermatologic oncologist.
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http://dx.doi.org/10.2217/fon-2021-0901DOI Listing
December 2021

Do Not Mess With Tattoos? Mohs Micrographic Surgery for Basal Cell Carcinoma Within the State of Texas.

Dermatol Surg 2021 09;47(9):1273-1275

Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1097/DSS.0000000000003087DOI Listing
September 2021

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis.

J Immunother Cancer 2021 08;9(8)

Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL).

Methods: Patients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks).

Results: Median duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001).

Conclusions: This is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement.

Trial Registration Number: ClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.
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http://dx.doi.org/10.1136/jitc-2021-002757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382148PMC
August 2021

Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma.

Cancer 2021 12 6;127(23):4413-4420. Epub 2021 Aug 6.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival.

Methods: The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation.

Results: A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P = .003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P = .429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates.

Conclusions: Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease.
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http://dx.doi.org/10.1002/cncr.33773DOI Listing
December 2021

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial.

Lancet Oncol 2021 06 14;22(6):848-857. Epub 2021 May 14.

Skin Cancer Center, Department of Dermatology, Harz Clinics, Quedlinburg, Germany.

Background: Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy.

Methods: We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov, NCT03132636, and is no longer recruiting new participants.

Findings: Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8-18). An objective response per independent central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including two partial responses that emerged at tumour assessments before the data cutoff and were confirmed by tumour assessments done subsequent to the data cutoff. The best overall response was five (6%) patients with a complete response and 21 (25%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 40 (48%) of 84 patients; the most common were hypertension (four [5%] of 84 patients) and colitis (four [5%]). Serious treatment-emergent adverse events occurred in 29 (35%) of 84 patients. There were no treatment-related deaths.

Interpretation: Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy.

Funding: Regeneron Pharmaceuticals and Sanofi.
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http://dx.doi.org/10.1016/S1470-2045(21)00126-1DOI Listing
June 2021

Exercise-Induced Vasculitis in a Patient With Negative Ultrasound Venous Reflux Study: A Mimic of Stasis Dermatitis.

Cutis 2021 Feb;107(2):E10-E11

Drs. Sundaresan and Silapunt are from the University of Texas McGovern Medical School, Houston. Dr. Silapunt is from the Department of Dermatology. Dr. Migden is from the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston.

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http://dx.doi.org/10.12788/cutis.0186DOI Listing
February 2021

Fixed Dose of Cemiplimab in Patients with Advanced Malignancies Based on Population Pharmacokinetic Analysis.

Adv Ther 2021 05 25;38(5):2365-2378. Epub 2021 Mar 25.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Introduction: This study outlined cemiplimab intravenous (IV) dosing strategy to move from body weight (BW)-based 3 mg/kg every-2-week (Q2W) dosing in first-in-human study (study 1423; NCT02383212) to fixed 350 mg every-3-week (Q3W) dosing, utilizing population pharmacokinetics (PopPK) modeling and simulations, and supported by a limited dataset from a phase 2 study (study 1540; NCT02760498).

Methods: Cemiplimab concentration data from a total of 505 patients were pooled from study 1423 in advanced malignancies and study 1540 in advanced cutaneous squamous cell carcinoma (CSCC). All patients received weight-based cemiplimab dose (1, 3, 10 mg/kg Q2W or 3 mg/kg Q3W) except 4% who received 200 mg Q2W. A linear two-compartment PopPK model incorporating covariates that improved goodness-of-fit statistics was developed to compare cemiplimab exposure at 350 mg Q3W versus 3 mg/kg Q2W. Upon availability, observed cemiplimab concentration at 350 mg Q3W in study 1540 was then compared with the simulated values.

Results: Post hoc estimates of cemiplimab exposure and variability (505 patients; weight range 30.9-156 kg; median 76.1 kg) at steady state were found to be similar at 350 mg Q3W and 3 mg/kg Q2W. Effect of BW on cemiplimab exposure was described by exposure versus BW plots and at extreme BW. Overlay of individual observed cemiplimab concentrations in 51 patients with metastatic CSCC on simulated concentration-time profiles in 2000 patients at 350 mg Q3W confirmed cemiplimab exposure similarity and demonstrated the robustness of dose optimization based on PopPK modeling and simulations.

Conclusions: Cemiplimab 350 mg Q3W is being further investigated in multiple indications.
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http://dx.doi.org/10.1007/s12325-021-01638-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107152PMC
May 2021

Integrating depth of invasion in T classification improves the prognostic performance of the American Joint Committee on Cancer primary tumor staging system for cutaneous squamous cell carcinoma of the head and neck.

Eur J Cancer 2021 02 22;144:169-177. Epub 2020 Dec 22.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients.

Methods: Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell's concordance index.

Results: Median age was 70 years (range, 19-97years) and median follow-up time of 22 months (range, 1-250months). The median DOI was 6.0 mm (range, 0.1-70.0 mm). The five-year DSS rate was 80.7% (95%CI, 77.4-83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01-1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves, model 6 surpassed the AJCC staging system.

Conclusions: Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients.

Lay Summary: The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling.

Precis: We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the American Joint Committee on Cancer after external validation.
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http://dx.doi.org/10.1016/j.ejca.2020.11.019DOI Listing
February 2021

Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck.

Cancer 2021 04 15;127(8):1238-1245. Epub 2020 Dec 15.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC.

Methods: This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models.

Results: No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195).

Conclusions: The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification.
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http://dx.doi.org/10.1002/cncr.33373DOI Listing
April 2021

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing.

J Immunother Cancer 2020 06;8(1)

Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Background: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).

Methods: The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.

Results: For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).

Conclusion: In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.

Trial Registration Number: Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498.
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http://dx.doi.org/10.1136/jitc-2020-000775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304829PMC
June 2020

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.

Lancet Oncol 2020 02 14;21(2):294-305. Epub 2020 Jan 14.

Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia.

Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma.

Methods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498.

Findings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1-15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32-55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia.

Interpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care.

Funding: Regeneron Pharmaceuticals and Sanofi.
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http://dx.doi.org/10.1016/S1470-2045(19)30728-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771329PMC
February 2020

CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma.

Future Oncol 2020 Feb 17;16(4):11-19. Epub 2020 Jan 17.

Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

In 2018, cemiplimab-rwlc became the first systemic treatment approved by the US FDA for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In 2019, conditional approvals were granted by Health Canada and the European Commission for the same indications. Limited data exist pertaining to the clinical characteristics, disease progression and survivorship of patients with advanced CSCC in real-world clinical practice. CemiplimAb-rwlc Survivorship and Epidemiology (CASE) is a prospective Phase IV, noninterventional, survivorship and epidemiology study that will enroll patients with advanced CSCC who have recently initiated or who plan to receive cemiplimab in a real-world setting. Trial registration number: NCT03836105.
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http://dx.doi.org/10.2217/fon-2019-0762DOI Listing
February 2020

Multiple inguinal basal cell carcinomas in the setting of intertrigo.

Indian J Dermatol Venereol Leprol 2020 Jul-Aug;86(4):469

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_769_18DOI Listing
April 2021

Severe pretibial myxedema refractory to systemic immunosuppressants.

Cutis 2019 Sep;104(3):E1-E3

University of Texas MD Anderson Cancer Center, Houston, USA.

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September 2019

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma.

Expert Rev Clin Pharmacol 2019 Oct 19;12(10):947-951. Epub 2019 Sep 19.

Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center , Houston , TX , USA.

: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. : We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. : Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.
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http://dx.doi.org/10.1080/17512433.2019.1665026DOI Listing
October 2019

Disseminated anaplastic pleomorphic xanthoastrocytoma with posttreatment fat necrosis during combined BRAF and MEK inhibitors therapy.

Pediatr Blood Cancer 2019 12 10;66(12):e27974. Epub 2019 Sep 10.

Pediatrics Neuro-oncology Program, MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1002/pbc.27974DOI Listing
December 2019

Review of systemic agents in the treatment of advanced cutaneous squamous cell carcinoma.

Future Oncol 2019 Sep 6;15(27):3171-3184. Epub 2019 Aug 6.

University of Texas MD Anderson Cancer Center, Department of Dermatology, Mohs and Dermasurgery Unit, Houston, TX 77030, USA.

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. The purpose of this article is to review the various systemic treatment options for advanced cSCC moving from the past to the present, highlighting their relative merits and shortcomings, and to briefly speculate on future developments in the field of advanced cSCC.
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http://dx.doi.org/10.2217/fon-2019-0158DOI Listing
September 2019

Treatment of Leg Veins for Restless Leg Syndrome: A Retrospective Review.

Cureus 2019 Apr 2;11(4):e4368. Epub 2019 Apr 2.

Dermatology, University of Texas McGovern Medical School, Houston, USA.

Background: Restless leg syndrome (RLS) and chronic venous insufficiency (CVI) share similar circadian timings and epidemiological characteristics.

Objective: The objective of the study was to investigate whether treating superficial venous reflux (SVR) improves the RLS severity in patients with CVI and whether there is an association of the RLS severity with the number of refluxed veins.

Materials And Methods: Patients with RLS and duplex ultrasound-proven SVR were identified from a database of 134 patients. All patients underwent endovenous radiofrequency ablation and ultrasound-guided foam sclerotherapy. International RLS (IRLS) rating scale questionnaires were reviewed to assess pre- and post-intervention RLS status.

Results: Thirty-five patients were identified. The average baseline IRLS score was 19.83 (moderate RLS) and improved to 7.89 (mild RLS) after treatment (p < .0001), corresponding to 63% decrease in symptoms. Ten patients (29%) had a follow-up score of 0, indicating complete relief of RLS symptoms. Twenty patients (57%) had decreased IRLS scores of 10 points or more (i.e. 1 grade level of severity). Six patients had no improvement. There was no association of the RLS severity with the number of refluxed veins.

Conclusion: The study found that correcting SVR improves RLS symptoms, suggesting an association between CVI and RLS. Venous ultrasound study and intervention should be considered for potential patients.
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http://dx.doi.org/10.7759/cureus.4368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551200PMC
April 2019

Correction to: Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

BMC Cancer 2019 04 18;19(1):366. Epub 2019 Apr 18.

Universitätsklinikum Schleswig-Holstein, Schittenhelmstr, 7, D-24 105, Kiel, Germany.

Following publication of the original article [1], it was reported that the legend for Fig. 1 was incomplete. The complete figure legend is.
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http://dx.doi.org/10.1186/s12885-019-5568-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474043PMC
April 2019

Angiotropism in recurrent cutaneous squamous cell carcinoma: Implications for regional tumor recurrence and extravascular migratory spread.

J Cutan Pathol 2019 Feb 11;46(2):152-158. Epub 2018 Dec 11.

Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, Texas.

Extravascular migratory metastasis is a form of cancer metastasis in which tumor cells spread by tracking along the abluminal aspect of vessel walls without breaking the vascular endothelial lining or intraluminal invasion. This phenomenon has been extensively described in melanoma and is being increasingly recognized in other neoplasms. Various modalities of treatment, including radiation-, chemo-, targeted-, and immune- therapies may potentially induce angiotropic behavior in neoplastic cells. Although there is a risk for tumor recurrence and metastasis, angiotropism may be under-recognized and is rarely reported. Here, we report a case of recurrent poorly-differentiated acantholytic squamous cell carcinoma of the scalp with extensive perineural invasion, previously treated with multiple therapies. There was multifocal extravascular cuffing of neoplastic cells around and focally involving the walls of small to medium-caliber blood vessels within and surrounding the tumor, without obvious tumor intravasation. In addition, small subtle nests of neoplastic keratinocytes were noted along the abluminal aspect of a large-caliber deep dermal blood vessel in an en-face margin, away from the main tumor mass. Such involvement can be difficult to identify; and thus, may be missed particularly during intra-operative frozen section evaluation, leading to false-negative margins and is therefore, a diagnostic pitfall.
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http://dx.doi.org/10.1111/cup.13388DOI Listing
February 2019

Emerging Nonsurgical Therapies for Locally Advanced and Metastatic Nonmelanoma Skin Cancer.

Dermatol Surg 2019 01;45(1):1-16

Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy.

Objective: To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC.

Materials And Methods: A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC.

Results: PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia.

Conclusion: Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.
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http://dx.doi.org/10.1097/DSS.0000000000001601DOI Listing
January 2019

PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.

N Engl J Med 2018 07 4;379(4):341-351. Epub 2018 Jun 4.

From the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston (M.R.M.), and South Texas Accelerated Research Therapeutics (START), San Antonio (K.P.P.) - both in Texas; the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (D.R., A.A.T.), the Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, VIC (A.G.), the Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA (A.M.L.), and Royal Brisbane and Women's Hospital and University of Queensland, Brisbane (B.G.M.H.) - all in Australia; the Department of Dermatology, Brigham and Women's Hospital (C.D.S.), the Department of Dermatology, Harvard Medical School (C.D.S.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (G.R.) - all in Boston; Schleswig-Holstein University Hospital, Kiel (A.H.), and University Hospital Essen, Essen and German Cancer Consortium, Essen (D.S.) - both in Germany; University of Colorado Denver, School of Medicine, Aurora (K.D.L.); the Departments of Head and Neck-Endocrine Oncology (C.H.C.) and Cutaneous Oncology (N.I.K.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis (L.H.-A.); the Department of Dermatology, Stanford University School of Medicine, Redwood City (A.L.S.C.), and the Division of Dermatology, City of Hope, Duarte (B.M.) - both in California; the Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York (L.A.D.), and Regeneron Pharmaceuticals, Tarrytown (F.S., M.M., K.M., G.D.Y., I.L., M.G.F.) - both in New York; Regeneron Pharmaceuticals, Basking Ridge, NJ (B.G., S.L., J.L., J.B., E.S.); University of Arizona Cancer Center, Tucson (H.M.B.), and Banner MD Anderson Cancer (J.H.) and the Department of Medical Oncology, Banner MD Anderson Cancer Center (J.N.), Gilbert - all in Arizona; Medical Oncology Department, Vall D'Hebron University Hospital (I.B.), and Institut Català D'Oncologia, Oncobell Program (IDIBELL), L'Hospitalet de Llobregat (M.G.-M.), Barcelona, and START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid (V.M.) - all in Spain; Sarah Cannon Research Institute, Nashville (M.L.J.); and the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta (T.K.O.).

Background: No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.

Methods: We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.

Results: In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.

Conclusions: Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
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http://dx.doi.org/10.1056/NEJMoa1805131DOI Listing
July 2018

A Nodular Hidradenoma of Atypical Location in Pregnancy.

Acta Derm Venereol 2018 Oct;98(9):908-909

University of Texas McGovern Medical School at Houston, , 77030 Houston, TX, USA.

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http://dx.doi.org/10.2340/00015555-2983DOI Listing
October 2018

Linear terra firma-forme dermatosis of the midline back.

Cutis 2018 Mar;101(3):205-206

Department of Dermatology, McGovern Medical School, University of Texas, Houston, USA.

Terra firma-forme dermatosis (TFFD) is a benign and likely underdiagnosed disorder with relatively few reports in the literature. A 46-year-old woman presented to our clinic with a 3-year history of linear TFFD extending from the upper sacrum to the midline upper back. It initially was thought to be acanthosis nigricans or lichen simplex chronicus, and a topical steroid cream was applied without success. The lesion ultimately was removed by rubbing with isopropyl alcohol, which confirmed a diagnosis of TFFD. Due to its ability to mimic other skin diseases, TFFD should be considered when patients present with hyperkeratotic hyperpigmented lesions.
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March 2018

Surgical site identification with personal digital device: A prospective pilot study.

J Am Acad Dermatol 2018 Sep 7;79(3):520-524. Epub 2018 Mar 7.

Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address:

Background: Various means to facilit ate accurate biopsy site identification have been proposed.

Objective: To determine the accuracy of biopsy site identification by using photographs taken with a patient's digital device by a dermatologist versus professional medical photography.

Methods: Photographs of circled biopsy sites were taken with personal digital devices by the principal investigator (PI). Another set of photographs was taken by a professional photographer. Secondary photographs were taken of the biopsy site location pointed to by the staff and PI on the basis of the personal digital device image and professional medical photography, respectively. On the basis of secondary photographs, 2 independent dermatologists determined whether the skin biopsy locations pointed out by the staff were consistent with the ones pointed out by PI.

Results: Per dermatologist A, the staff correctly identified all 53 biopsy sites. Per dermatologist B, the staff were correct on 51 of 53 observations. Dermatologist C, the final arbiter, concurred with dermatologist A on the 2 cases in which dermatologist B was not certain of the location of the biopsy site.

Limitations: The mean interval from initial biopsy to reidentification of the site was 36.2 days.

Conclusion: Utilizing patients' personal digital devices is a cost-effective, Health Insurance Portability and Accountability Act-compliant, and readily available means to identify skin biopsy sites.
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http://dx.doi.org/10.1016/j.jaad.2018.02.069DOI Listing
September 2018

Multiple eccrine spiradenomas in a zosteriform pattern.

Dermatol Online J 2017 Aug 15;23(8). Epub 2017 Aug 15.

Department of Dermatology, University of Texas McGovern Medical School at Houston, Houston, Texas,.

Eccrine spiradenoma (ES) typically presents as a solitary tender lesion. Multiple ES is a rare variant of ES and can present in a segmental, linear, blaschkoid, or zosteriform pattern. The etiology of multiple ES is unknown, but several theories have been suggested including a multipotent stem cell origin. We report the case of a 30-year-old woman with multiple painful ES in a zosteriform pattern on the mid-back and abdomen. Skin biopsy of a representative lesion demonstrated a circumscribed tumor nodule encapsulated by a fibrous capsule with diffuse dense basophilic proliferation located in the dermis. The lesions were then excised on two separate sessions without recurrence.
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August 2017

Emerging trends in the treatment of advanced basal cell carcinoma.

Cancer Treat Rev 2018 Mar 14;64:1-10. Epub 2017 Dec 14.

Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.

Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer worldwide. In most patients, BCC can be effectively treated with standard surgical excision, Mohs micrographic surgery, curettage and electrodessication, radiotherapy, and/or superficial field therapies (including 5-fluorouracil, imiquimod, and photodynamic therapy); however, a minority of patients develop advanced BCC, for which treatment can be challenging and outcomes are poorer. Advanced BCC encompasses a heterogeneous assortment of cases, including metastatic BCC as well as locally advanced BCC (for which no formal definition exists but which generally includes large, deep, aggressive, or recurrent tumors). Locally advanced BCC may be broadly categorized as cases for which (further) surgery is considered inappropriate or would be substantially disfiguring and radiation is considered inappropriate as a single modality or second-line treatment. Several therapies are being investigated for the treatment of advanced BCC. In particular, hedgehog pathway inhibitors have emerged as an important treatment option for this population. Two hedgehog pathway inhibitors-vismodegib and sonidegib-have received regulatory approval for the treatment of certain subsets of patients with advanced BCC after demonstrating clinical efficacy and safety in large, international phase 2 clinical trials. Here we review the available treatment options for BCC, focusing on the treatment of advanced BCC. Clinical data from studies evaluating vismodegib and sonidegib in patients with advanced BCC are also discussed. As more clinical trial and real-world data on the use of hedgehog pathway inhibitors become available, better-informed decisions can be made for the treatment of patients with advanced BCC.
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http://dx.doi.org/10.1016/j.ctrv.2017.12.009DOI Listing
March 2018
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