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Metastatic cutaneous squamous cell carcinoma responsive to cemiplimab in a patient with multiple myeloma. JAAD case reports Marukian, N. V., Lin, J. Q., Colevas, A. D., Coutre, S., Chang, A. L. 2020; 6 (9): 819?21
View details for DOI 10.1016/j.jdcr.2020.06.036

View details for PubMedID 32875028
IL-1 beta is a potential central mediator to Papulopustular Rosacea pathology as determined by paired transcriptomic and proteomic analysis Harden, J., Shih, Y., Rajendran, D., Xu, J., Li, R., Hofland, H., Chang, A. L. ELSEVIER SCIENCE INC. 2020: S114
View details for Web of Science ID 000554564400712
In-progress validation of candidate rosacea genes by targeted interrogation of alleles and assessment of rosacea comorbidities Kumar, A., Shih, Y., Chiou, A., Li, S., Chang, A. L. ELSEVIER SCIENCE INC. 2020: S33
View details for Web of Science ID 000554564400253
Phase II study of cemiplimab in patients (pts) with advanced cutaneous squamous cell carcinoma (CSCC): Longer follow-up. Rischin, D., Khushalani, N. I., Schmults, C. D., Guminski, A., Chang, A. S., Lewis, K. D., Lim, A., Hernandez-Aya, L., Hughes, B., Schadendorf, D., Hauschild, A., Stankevich, E., Booth, J., Li, S., Chen, Z., Okoye, E., Lowy, I., Fury, M. G., Migden, M. AMER SOC CLINICAL ONCOLOGY. 2020
View details for Web of Science ID 000560368300123
Health-related quality of life (HRQL) in patients with advanced cutaneous squamous cell carcinoma (CSCC) treated with cemiplimab: Post hoc exploratory analyses of a phase II clinical trial. Migden, M., Rischin, D., Sasane, M., Mastey, V., Pavlick, A., Schmults, C. D., Chen, Z., Guminski, A., Hauschild, A., Bury, D., Chang, A. S., Rabinowits, G., Ibrahim, S. F., Lowy, I., Fury, M. G., Li, S., Chen, C. AMER SOC CLINICAL ONCOLOGY. 2020
View details for Web of Science ID 000560368300139
An exploratory, open-label, investigator-initiated study of interleukin-17A (IL-17A) blockade in patients with moderate to severe papulopustular rosacea. The British journal of dermatology Kumar, A. M., Chiou, A. S., Shih, Y. H., Li, S., Chang, A. L. 2020
Abstract

Currently, few systemic medications are effective for rosacea.1 Recent research has shown elevation of interleukin (IL)-17A in rosacea.2,3 To assess if the IL-17A inhibitor,4, 5 secukinumab, could improve moderate to severe papulopustular rosacea (PPR), an exploratory, open-label, single-arm investigator initiated clinical trial in adults with moderate to severe PPR was performed after Stanford Human Subjects Panel approval.

View details for DOI 10.1111/bjd.19172

View details for PubMedID 32364247
Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. The Lancet. Oncology Migden, M. R., Khushalani, N. I., Chang, A. L., Lewis, K. D., Schmults, C. D., Hernandez-Aya, L., Meier, F., Schadendorf, D., Guminski, A., Hauschild, A., Wong, D. J., Daniels, G. A., Berking, C., Jankovic, V., Stankevich, E., Booth, J., Li, S., Weinreich, D. M., Yancopoulos, G. D., Lowy, I., Fury, M. G., Rischin, D. 2020
Abstract

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.

View details for DOI 10.1016/S1470-2045(19)30728-4

View details for PubMedID 31952975
A PHASE 2, MULTI-Center, PLACEBO-CONTROLLED STUDY OF Single dose Squaric Acid Dibutyl Ester (sadbe) to reduce frequency of outbreaks IN SUBJECTS WITH RECURRENT HERPES LABIALIS. Journal of the American Academy of Dermatology Chang, A. L., Honari, G., Guan, L., Zhao, L., Palli, M. A., Horn, T. D., Dudek, A. Z., McTavish, H. 2020
View details for DOI 10.1016/j.jaad.2020.04.021

View details for PubMedID 32289388
Paired Transcriptomic and Proteomic Analysis Implicates IL-1? in the Pathogenesis of Papulopustular Rosacea Explants. The Journal of investigative dermatology Harden, J. L., Shih, Y. H., Xu, J., Li, R., Rajendran, D., Hofland, H., Chang, A. L. 2020
Abstract

Papulopustular rosacea (PPR) is a chronic inflammatory skin disease with limited treatment options. Although multiple pathways have been described to be upregulated in PPR, a mechanistic understanding of the key drivers and interaction between pathways in PPR pathology is lacking. In this study, we utilized PPR biopsy explants to integrate both differentially expressed genes (DEGs) and differently expressed proteins (DEPs) in paired non-lesional (NL) and lesional (LS) PPR tissue (n=5 patients). The results of this study identified 92 DEGs and 20 DEPs between paired PPR LS and NL explants. MAPK and TNF signaling pathways were the most significantly upregulated pathways in PPR LS tissue and aligned with DEPs identified in this study. Both MAPK and TNF signaling pathways highlighted IL-1? as a potential central mediator to PPR pathogenesis. In support of this, stimulation of NL explants with IL-1? resulted in a transcriptomic and proteomic profile similar to LS PPR. In this integrative transcriptomic and quantitative protein analysis, we identified several inflammatory genes, proteins, and pathways which may be contributing to PPR, as well as highlighted a potential role of IL-1? in driving inflammation in PPR.

View details for DOI 10.1016/j.jid.2020.08.013

View details for PubMedID 32941918
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. Journal for immunotherapy of cancer Rischin, D., Migden, M. R., Lim, A. M., Schmults, C. D., Khushalani, N. I., Hughes, B. G., Schadendorf, D., Dunn, L. A., Hernandez-Aya, L., Chang, A. L., Modi, B., Hauschild, A., Ulrich, C., Eigentler, T., Stein, B., Pavlick, A. C., Geiger, J. L., Gutzmer, R., Alam, M., Okoye, E., Mathias, M., Jankovic, V., Stankevich, E., Booth, J., Li, S., Lowy, I., Fury, M. G., Guminski, A. 2020; 8 (1)
Abstract

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).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.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%).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.Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498.

View details for DOI 10.1136/jitc-2020-000775

View details for PubMedID 32554615
Impact of prior lines of systemic therapy (PST) on the efficacy of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with advanced cutaneous squamous cell carcinoma (CSCC) Rischin, D., Khushalani, N. I., Schmults, C. D., Guminski, A., Chang, A. S., Lewis, K. D., Lim, A. M., Hernandez-Aya, L., Hughes, B. M., Schadendorf, D., Hauschild, A., Stankevich, E., Booth, J., Li, S., Chen, Z., Desai, J., Lowy, I., Fury, M. G., Migden, M. R. OXFORD UNIV PRESS. 2019
View details for Web of Science ID 000506799900105
KEYNOTE-630: phase 3 study of adjuvant pembrolizumab versus placebo in patients with high-risk, locally advanced cutaneous squamous cell carcinoma Geiger, J., Daniels, G., Cohen, E., Ge, J., Gumuscu, B., Swaby, R., Chang, A. BMC. 2019
View details for Web of Science ID 000496473200876
Alterations of Immune and Keratinization Gene Expression in Papulopustular Rosacea by Whole Transcriptome Analysis. The Journal of investigative dermatology Shih, Y., Xu, J., Kumar, A., Li, R., Chang, A. L. 2019
View details for DOI 10.1016/j.jid.2019.09.021

View details for PubMedID 31705873
Phase II study of 2 dosing regimens of cemiplimab, a human monoclonal anti-PD-1, in metastatic cutaneous squamous cell carcinoma (mCSCC) Rischin, D., Lim, A. M., Schmults, C. D., Khushalani, N. I., Hughes, B. G., Schadendorf, D., Dunn, L. A., Chang, A. S., Hauschild, A., Ulrich, C., Eigentler, T., Migden, M. R., Pavlick, A. C., Geiger, J., Stankevich, E., Li, S., Lowy, I., Fury, M. G., Guminski, A. OXFORD UNIV PRESS. 2019
View details for Web of Science ID 000491295503363
Exploratory study to examine the gene expression effects of retinol on aging-related molecular pathways in individuals of East Asian descent Guan, L., Zhao, L., Xu, J., Li, R., Kern, D., Knaggs, H., Chang, A. S. MOSBY-ELSEVIER. 2019: AB64
View details for Web of Science ID 000482195000217
A phase 1b, open-label, investigator-initiated, proof-of-concept study of pembrolizumab for advanced basal cell carcinomas Chang, A., Duy Tran, Cannon, J., Li, S., Jeng, M., Rieger, K., Reddy, S., Sarin, K., Colevas, D. MOSBY-ELSEVIER. 2019: AB8
View details for Web of Science ID 000482195000029
Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase 2 randomised, double-blind BOLT study. The British journal of dermatology Dummer, R., Guminksi, A., Gutzmer, R., Lear, J. T., Lewis, K. D., Chang, A. L., Combemale, P., Dirix, L., Kaatz, M., Kudchadkar, R., Loquai, C., Plummer, R., Schulze, H., Stratigos, A. J., Trefzer, U., Squittieri, N., Migden, M. R. 2019
Abstract

BACKGROUND: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT (Basal Cell Carcinoma Outcomes with LDE225 [sonidegib] Treatment) study.PURPOSE: This is the final 42-month analysis of the BOLT study evaluating sonidegib efficacy and safety.METHODS: Adults with no prior hedgehog pathway inhibitor therapy were randomised in a 1:2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. Primary efficacy endpoint was objective response rate (ORR) by central review, assessed at baseline, weeks 5, 9, and 17, then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety endpoints included adverse event monitoring and reporting.RESULTS: The study enrolled 230 patients, 79 and 151 in the 200 mg and 800 mg groups, respectively, of whom 8% and 3% remained on treatment by the 42-month cutoff, respectively. The ORR by central review (95% confidence interval [CI]) was 56�1 (43�3-68�3)% for laBCC and 7�7 (0�2-36�0)% for mBCC in the 200 mg group and 46�1 (37�2-55�1)% for laBCC and 17�4 (5�0-38�8)% for mBCC in the 800 mg group. No new safety concerns emerged.CONCLUSIONS: Sonidegib demonstrated sustained efficacy and a manageable safety profile. Final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC.

View details for DOI 10.1111/bjd.18552

View details for PubMedID 31545507
Quantitative analysis of differentially expressed proteins in papulopustular rosacea Harden, J., Shih, Y., Rajendran, D., Hofland, H., Chang, A. ELSEVIER SCIENCE INC. 2019: B25
View details for DOI 10.1016/j.jid.2019.06.117

View details for Web of Science ID 000482187300133
An exploratory open label phase 1b study of secukinumab in patients with moderate to severe papulopustular rosacea Kumar, A., Chiou, A., Shih, Y., Li, S., Chang, A. ELSEVIER SCIENCE INC. 2019: B15
View details for DOI 10.1016/j.jid.2019.06.071

View details for Web of Science ID 000482187300093
Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma Chiang, A., Tan, C., Kuonen, F., Hodgkinson, L., Chiang, F., Cho, R., Tang, J., Chang, A., Rieger, K., Oro, A., Sarin, K. ELSEVIER SCIENCE INC. 2019: S295
View details for DOI 10.1016/j.jid.2019.07.521

View details for Web of Science ID 000485661500467
Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma AMERICAN JOURNAL OF CLINICAL DERMATOLOGY Patel, R., Chang, A. S. 2019; 20 (4): 477?82
View details for DOI 10.1007/s40257-019-00426-w

View details for Web of Science ID 000480501600001
Incidence of Perineural Invasion with Hedgehog Pathway Inhibitors in Orbital and Periorbital Basal Cell Carcinoma Chandramohan, A., Nair, A., Chang, A., Kossler, A. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800700159
KEYNOTE-630: Phase 3 study of adjuvant pembrolizumab versus placebo in patients with high risk, locally advanced cutaneous squamous cell carcinoma. Geiger, J., Daniels, G. A., Cohen, E. W., Ge, J., Gumuscu, B., Swaby, R. F., Chang, A. S. AMER SOC CLINICAL ONCOLOGY. 2019
View details for DOI 10.1200/JCO.2019.37.15_suppl.TPS9597

View details for Web of Science ID 000487345803476
Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (IaCSCC). Migden, M., Khushalani, N. I., Chang, A. S., Rischin, D., Schmults, C. D., Hernandez-Aya, L., Meier, F., Schadendorf, D., Guminski, A., Hauschild, A., Wong, D. L., Daniels, G. A., Berking, C., Jankovic, V., Stankevich, E., Booth, J., Li, S., Lowy, I., Fury, M. G., Lewis, K. D. AMER SOC CLINICAL ONCOLOGY. 2019
View details for DOI 10.1200/JCO.2019.37.15_suppl.6015

View details for Web of Science ID 000487345805599
Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with metastatic cutaneous squamous cell carcinoma (mCSCC; Group 1): 12-month follow-up. Guminski, A., Lim, A., Khushalani, N. I., Schmults, C. D., Hernandez-Aya, L., Modi, B., Dunn, L., Hughes, B., Chang, A. S., Hauschild, A., Migden, M., Gutzmer, R., Alam, M., Jankovic, V., Stankevich, E., Booth, J., Li, S., Lowy, I., Fury, M. G., Rischin, D. AMER SOC CLINICAL ONCOLOGY. 2019
View details for DOI 10.1200/JCO.2019.37.15_suppl.9526

View details for Web of Science ID 000487345806580
Pembrolizumab with or without vismodegib for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study Chang, A., Tran, D. C., Cannon, J., Li, S., Jeng, M., Rieger, K., Sarin, K. Y., Yost, K., Satpathy, A., Reddy, S., Colevas, A. ELSEVIER SCIENCE INC. 2019: S92
View details for Web of Science ID 000465561503249
Alterations of gene expression in papulopustular rosacea by whole transcriptome analysis Shih, Y., Xu, J., Kumar, A., Li, R., Chang, A. ELSEVIER SCIENCE INC. 2019: S170
View details for Web of Science ID 000465561505123
Exploratory study to examine the gene expression effects of topical retinol on aging-related pathways in individuals of East Asian descent Guan, L., Zhao, L., Xu, J., Li, R., Kern, D., Knaggs, H., Chang, A. ELSEVIER SCIENCE INC. 2019: S117
View details for Web of Science ID 000465561504110
Interim analysis of phase 2 results for Cemiplimab, a human monoclonal antibody to programmed death-1 (PD-1), in patients with locally advanced cutaneous squamous cell carcinoma Migden, M. R., Berking, C., Chang, A. S., Eigentler, T. K., Hauschild, A., Hernandez-Aya, L., Khushalani, N., Lewis, K. D., Meier, F., Modi, B., Rischin, D., Schadendorf, D., Schmults, C. D., Ulrich, C., Booth, J., Li, S., Mohan, K., Stankevich, E., Lowy, Fury, M. G. WILEY. 2019: 161?62
View details for Web of Science ID 000466398500388
Unique Tumor Heterogeneity Within a Single Locally Advanced Basal Cell Carcinoma Resulting in a Partial Response Despite Continuous Vismodegib Treatment DERMATOLOGIC SURGERY Nayyar, P., Chang, A. S., Sarin, K., Ratner, D. 2019; 45 (4): 608?10
View details for DOI 10.1097/DSS.0000000000001607

View details for Web of Science ID 000480739500020

View details for PubMedID 30045109
Enhancer Connectome Nominates Target Genes of Inherited Risk Variants from Inflammatory Skin Disorders JOURNAL OF INVESTIGATIVE DERMATOLOGY Jeng, M. Y., Mumbach, M. R., Granja, J. M., Satpathy, A. T., Chang, H. Y., Chang, A. S. 2019; 139 (3): 605?14
View details for DOI 10.1016/j.jid.2018.09.011

View details for Web of Science ID 000459158400026
Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma. American journal of clinical dermatology Patel, R., Chang, A. L. 2019
Abstract

Cutaneous squamous cell carcinoma (CSCC) is one of the most common human malignancies, and the incidence is increasing with time. High mutational loads, known infiltration with lymphocytes, and programmed death (PD)-ligand 1 (PD-L1) expression suggest that immune checkpoint inhibitors, suchas PD-1 inhibitors, may show utility in treating CSCC, similar to response see in other solid tumor types. Recently, the robust responsiveness of CSCCs to the PD-1 inhibitor cemiplimab was revealed in the results of a combined phase I/II clinical trial, with an overall response rate of 50% and a durable response exceeding 6months in 57% of responders. Compared to prior systemic therapies with scant data for efficacy and safety, cemiplimab is a breakthrough therapy, the first systemic drug approved for advanced CSCCs. Other immune checkpoint inhibitors have shown promise through case reports and series, and are currently in clinical development for CSCCs.

View details for PubMedID 30737731
Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chang, A. S., Tran, D. C., Cannon, J. D., Li, S., Jeng, M., Patel, R., Van der Bokke, L., Pague, A., Brotherton, R., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S., Sarin, K., Colevas, A. 2019; 80 (2): 564?66
View details for DOI 10.1016/j.jaad.2018.08.017

View details for Web of Science ID 000455473200042
Reply to: "Use of immortal time within survival analysis" JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Lee, C., Li, S., Duy Cong Tran, Zhu, G., Kim, J., Kwong, B. Y., Chang, A. S. 2019; 80 (1): E19?E20
View details for DOI 10.1016/j.jaad.2018.08.042

View details for Web of Science ID 000452985600009
Long term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase 2, randomised, double-blind BOLT study British Journal of Dermatology Dummer, R., Guminski, A., Gutzmer, R., Lear, J., Lewis, K., Chang, A. S., Combemale, P., Dirix, L., Kaatz, M., Kudchadkar, R., Loquai, C., Plummer, R., Schulze, H., Stratigos, A., Trefzer, U., Squitteri, N., Migden, M. 2019; Accepted (TBD)
Clonal replacement of tumor-specific T cells following PD-1 blockade. Nature Medicine 2019. 25(8):1251-9. Nature Medicine Yost, K. E., Satpathy, A., Wells, D. K., Qi, Y., Wang, C., Kageyama, R., McNamara, K., Granja, J. M., Sarin, K., Brown, R. A., Gupta, R., Curtis, C., Bucktrout, S. L., Davis, M. M., Chang, A. S., Chang, H. Y. 2019; 25 (8)
Alterations of immune and keratinization gene expression in papulopustular rosacea by whole transcriptome analysis Journal of Investigative Dermatology Shih, Y., Xu, J., Kumar, A., Chang, A. S. 2019; Accepted (TBD)
Pathophysiology of basal cell carcinoma and its associated genetic syndromes Basal cell carcinoma-- advances in treatment and research Chang, A. S. Springer. 2019; TBD
Clonal replacement of tumor-specific T cells following PD-1 blockade. Nature medicine Yost, K. E., Satpathy, A. T., Wells, D. K., Qi, Y., Wang, C., Kageyama, R., McNamara, K. L., Granja, J. M., Sarin, K. Y., Brown, R. A., Gupta, R. K., Curtis, C., Bucktrout, S. L., Davis, M. M., Chang, A. L., Chang, H. Y. 2019
Abstract

Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of patients with cancer1. However, whether the T cell response to checkpoint blockade relies on reinvigoration of pre-existing tumor-infiltrating lymphocytes or on recruitment of novel T cells remains unclear2-4. Here we performed paired single-cell RNA and T cell receptor sequencing on 79,046 cells from site-matched tumors from patients with basal or squamous cell carcinoma before and after anti-PD-1 therapy. Tracking T cell receptor clones and transcriptional phenotypes revealed coupling of tumor recognition, clonal expansion and T cell dysfunction marked by clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, the expansion of T cell clones did not derive from pre-existing tumor-infiltrating T lymphocytes; instead, the expanded clones consisted of novel clonotypes that had not previously been observed in the same tumor. Clonal replacement of T cells was preferentially observed in exhausted CD8+ T cells and evident in patients with basal or squamous cell carcinoma. These results demonstrate that pre-existing tumor-specific T cells may have limited reinvigoration capacity, and that the T cell response to checkpoint blockade derives from a distinct repertoire of T cell clones that may have just recently entered the tumor.

View details for DOI 10.1038/s41591-019-0522-3

View details for PubMedID 31359002
Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nature biotechnology Satpathy, A. T., Granja, J. M., Yost, K. E., Qi, Y., Meschi, F., McDermott, G. P., Olsen, B. N., Mumbach, M. R., Pierce, S. E., Corces, M. R., Shah, P., Bell, J. C., Jhutty, D., Nemec, C. M., Wang, J., Wang, L., Yin, Y., Giresi, P. G., Chang, A. L., Zheng, G. X., Greenleaf, W. J., Chang, H. Y. 2019; 37 (8): 925?36
Abstract

Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here, we assess the performance of a massively parallel droplet-based method for mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq). We apply scATAC-seq to obtain chromatin profiles of more than 200,000 single cells in human blood and basal cell carcinoma. In blood, application of scATAC-seq enables marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity and reconstruction of trajectories of cellular differentiation. In basal cell carcinoma, application of scATAC-seq reveals regulatory networks in malignant, stromal and immune cells in the tumor microenvironment. Analysis of scATAC-seq profiles from serial tumor biopsies before and after programmed cell death protein 1 blockade identifies chromatin regulators of therapy-responsive T cell subsets and reveals a shared regulatory program that governs intratumoral CD8+ T cell exhaustion and CD4+ T follicular helper cell development. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems.

View details for DOI 10.1038/s41587-019-0206-z

View details for PubMedID 31375813
Old fibroblasts secrete inflammatory cytokines that drive variability in reprogramming efficacy between individuals and could affect wound healing Nature Mahmoudi, S., Mancini, E., Moore, A., Jahanbani, F., Hebstreit, K., Srinavasan, R., Li, X., Devarajan, K., Prelo, L., Ang, C., Shibuya, Y., Benayoun, B. A., Chang, A. S., Wernig, M., Wysocka, J., Longaker, M. T., Snyder, M., Brunet, A. 2019; Accepted
Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma Journal of Investigative Dermatology Chiang, A., Tan, C. Z., Kuonen, F., Hodgkinson, L. M., Chiang, F., Cho, R. J., South, A. P., Tang, J. Y., Chang, A. L., Rieger, K. E., Oro, A. E., Sarin, K. Y. 2019
View details for DOI 10.1016/j.jid.2019.03.1163
Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing. Nature Mahmoudi, S., Mancini, E., Xu, L., Moore, A., Jahanbani, F., Hebestreit, K., Srinivasan, R., Li, X., Devarajan, K., Pr�lot, L., Ang, C. E., Shibuya, Y., Benayoun, B. A., Chang, A. L., Wernig, M., Wysocka, J., Longaker, M. T., Snyder, M. P., Brunet, A. 2019; 574 (7779): 553?58
Abstract

Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing1, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing2,3. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has implications for regenerative medicine and rejuvenation strategies4. Here we show that fibroblast cultures from old mice secrete inflammatory cytokines and exhibit increased variability in the efficiency of iPS cell reprogramming�between mice. Variability between individuals is emerging as a feature of old age5-8, but the underlying mechanisms remain unknown. To identify drivers of this variability, we performed multi-omics profiling of fibroblast cultures from young and old mice that have different reprogramming efficiencies. This approach revealed that fibroblast cultures from old mice contain 'activated fibroblasts' that secrete inflammatory cytokines, and that the proportion of activated fibroblasts in a culture correlates with the reprogramming efficiency of that culture. Experiments in which conditioned medium was swapped between cultures showed that extrinsic factors secreted by activated fibroblasts underlie part of the variability between mice in reprogramming efficiency, and we have identified inflammatory cytokines, including TNF, as key contributors. Notably, old mice also exhibited variability in wound healing rate in vivo. Single-cell RNA-sequencing analysis identified distinct subpopulations of fibroblasts with different cytokine expression and signalling in the wounds of old mice with slow versus fast healing rates. Hence, a shift in fibroblast composition, and the ratio of inflammatory cytokines that they secrete, may drive the variability between mice in reprogramming in vitro and influence wound healing rate in vivo. This variability may reflect distinct stochastic ageing trajectories between individuals, and could help in developing personalized strategies to improve iPS cell generation and wound healing in elderly individuals.

View details for DOI 10.1038/s41586-019-1658-5

View details for PubMedID 31645721
Enhancer connectome nominates target genes of inherited risk variants from inflammatory skin disorders. The Journal of investigative dermatology Jeng, M. Y., Mumbach, M. R., Granja, J. M., Satpathy, A. T., Chang, H. Y., Chang, A. L. 2018
Abstract

The vast majority of polymorphisms for human dermatologic diseases fall in non-coding DNA regions, leading to difficulty interpreting their functional significance. Recent work utilizing chromosome conformation capture (3C) technology in combination with chromatin immunoprecipitation (ChIP) has provided a systematic means of linking non-coding variants within active enhancer loci to putative gene targets. Here, we apply H3K27ac HiChIP high-resolution contact maps, generated from primary human T-cell subsets (CD4+ Naive, TH17, and Treg), to 21 dermatologic conditions associated with single nucleotide polymorphisms (SNPs) from 106 genome-wide association studies (GWAS). This "enhancer connectome" identified 1,492 HiChIP gene-targets from 542 non-coding SNPs (p<5.0x10-8). SNP-containing enhancers from inflammatory skin conditions were significantly enriched within the human leukocyte antigen (HLA)-locus, and also targeted several key factors from the JAK-STAT signaling pathway, while non-immune conditions did not. A focused profiling of systemic lupus erythematosus (SLE) HiChIP-genes identified enhancer interactions with factors important for effector CD4+ T-cell differentiation and function, including interferon regulatory factor 8 (IRF8) and members of the Ikaros family of zinc-finger proteins. Our results demonstrate the ability of the enhancer connectome to nominate functionally-relevant candidates from GWAS-identified variants, representing a powerful tool to guide future studies into the genomic regulatory mechanisms underlying dermatologic diseases.

View details for PubMedID 30315781
Response to the Letter to the Editor entitled, "Use of immortal time within survival analysis": JAAD-D-18-01157. Journal of the American Academy of Dermatology Min Lee, C. K., Li, S., Tran, D. C., Zhu, G. A., Kim, J., Kwong, B. Y., Chang, A. L. 2018
View details for PubMedID 30205131
An exploratory, open-label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas Duy Tran, Zhu, A., Chang, A. MOSBY-ELSEVIER. 2018: AB38
View details for Web of Science ID 000440565900146
Differences in skin aging characteristics in women of East Asian versus European descent residing in the same geographic location Guan, L., Zhu, A., Li, S., Montana, M., Kern, D., Knaggs, H., Chang, A. MOSBY-ELSEVIER. 2018: AB108
View details for Web of Science ID 000440565900414
Levocarnitine for vismodegib-associated muscle spasms: A pilot randomized, double-blind, placebo-controlled, investigator-initiated trial Chang, A., Cannon, J., Tran, D., Li, S. MOSBY-ELSEVIER. 2018: AB178
View details for Web of Science ID 000440565901207
Retrospective comparison of the clinical effects of programmed death protein 1 inhibitors to treat melanoma versus nonmelanoma skin cancer Jin, M., Li, S., Duy Tran, Henry, S., Wood, D., Chang, A. MOSBY-ELSEVIER. 2018: AB246
View details for Web of Science ID 000440565901464
A case of combination PD-1 inhibitor and intralesional 5-fluorouracil for high-frequency nonmelanoma skin cancers in an immunocompromised patient Duy Tran, Lee, C., Colevas, A., Chang, A. MOSBY-ELSEVIER. 2018: AB6
View details for Web of Science ID 000440565900023
Reaction patterns of dermatitis arising during PD-1/PD-L1 inhibitor therapy and association with tumor response Lee, C., Li, S., Zhu, A., Kim, J., Duy Tran, Kwong, B., Chang, A. MOSBY-ELSEVIER. 2018: AB239
View details for Web of Science ID 000440565901438
Recurrence outcomes for nonmelanoma skin cancer after adjuvant radiation Cannon, J., Li, S., Chang, A. MOSBY-ELSEVIER. 2018: AB241
View details for Web of Science ID 000440565901445
Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility JCI INSIGHT Cho, H. G., Kuo, K. Y., Li, S., Bailey, I., Aasi, S., Chang, A. S., Oro, A. E., Tang, J. Y., Sarin, K. Y. 2018; 3 (15)
Abstract

Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes. In parallel, a case-control retrospective review was performed to interrogate the association of malignancies with frequent BCC development in a large US medical insurance claims database (Truven), which included 13,264 individuals with 6 or more BCCs from 2007 to 2011. 19.7% of the frequent BCC cohort harbored pathogenic mutations in DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. Individuals with 6 or more BCCs had an increased risk of other malignancies, with a 3.5-fold increase in the frequent BCC cohort and a 3.2-fold increase in the Truven database. Individuals who developed frequent BCCs have an increased prevalence of germline mutations in DNA repair genes and increased malignancy risk. Our data implicate frequent BCC development as an external marker of inherited cancer risk.

View details for DOI 10.1172/jci.insight.122744

View details for Web of Science ID 000441201300022

View details for PubMedID 30089731
Unintended widespread facial autoinoculation of varicella by home microneedling roller device. JAAD case reports Leatham, H., Guan, L., Chang, A. L. 2018; 4 (6): 546?47
View details for PubMedID 29892671
Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator-initiated trial JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY Cannon, J. D., Tran, D. C., Li, S., Chang, A. S. 2018; 32 (7): E298?E299
View details for DOI 10.1111/jdv.14844

View details for Web of Science ID 000436252800029
Genetic fine-mapping of the Iowan SNCA gene triplication in a patient with Parkinson's disease NPJ PARKINSONS DISEASE Zafar, F., Valappil, R., Kim, S., Johansen, K. K., Chang, A. S., Tetrud, J. W., Eis, P. S., Hatchwell, E., Langston, J., Dickson, D. W., Schule, B. 2018; 4: 18
Abstract

The "Iowa kindred," a large Iowan family with autosomal-dominant Parkinson's disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7?Mb triplication of the alpha-synuclein genomic locus. Affected individuals present with an early-onset, severe parkinsonism-dementia syndrome. Here, we present a descendant of the Iowa kindred with novel, disease-associated non-motor findings of reduced heart rate variability, complete anosmia, and a rare skin condition called colloid milium. At autopsy, key neuropathological findings were compatible with diffuse Lewy body disease. Using high-resolution comparative genomic hybridization (CGH) array analysis to fine-map the genomic breakpoints, we observed two independent recombination events of the SNCA locus that resulted in a genomic triplication of twelve genes, including SNCA, and the disruption of two genes, HERC6 and CCSER1, at the genomic breakpoints. In conclusion, we provide further evidence that the mere two-fold overexpression of alpha-synuclein leads to a fulminant alpha-synucleinopathy with rapid progression and severe clinical and neuropathological features.

View details for PubMedID 29928688
Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study. Journal of the American Academy of Dermatology Min Lee, C. K., Li, S., Tran, D. C., Zhu, G. A., Kim, J., Kwong, B. Y., Chang, A. L. 2018
Abstract

BACKGROUND: Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.OBJECTIVE: (s): To assess the nature of dermatitis after PD-1/PD-L1 inhibitor exposure and oncologic outcomes associated with dermatitis.METHODS: Retrospective, matched, case-control study conducted at a single academic center.RESULTS: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). Overall tumor response rate was 65.0% for cases and 17.0% for controls (p=0.0007), odds ratio: 7.3 (95% CI 2.3-23.1). Progression Free Survival (PFS) and Overall Survival (OS) times were significantly longer for cases than controls by Kaplan-Meier analysis (p<0.0001 and 0.0203, respectively).LIMITATIONS: Retrospective design and relatively small sample size precluded matching on all cancer types.CONCLUSION: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The predictive value of PD-1/PD-L1 related dermatitis on cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

View details for PubMedID 29857011
Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC) Rischin, D., Migden, M., Chang, A., Chung, C. H., Dunn, L., Guminski, A., Hauschild, A., Hernandez-Aya, L., Hughes, B., Lewis, K. D., Lim, A., Modi, B., Schadendorf, D., Schmults, C., Booth, J., Li, S., Mohan, K., Stankevich, E., Lowy, I., Fury, M. G. AMER SOC CLINICAL ONCOLOGY. 2018
View details for DOI 10.1200/JCO.2018.36.15_suppl.9519

View details for Web of Science ID 000442916003296
Association of tumor response to PD-1/PD-L1 immunotherapy and type of dermatitis that arises after the immunotherapy Lee, C., Li, S., Tran, D., Zhu, A., Kim, J., Kwong, B., Chang, A. ELSEVIER SCIENCE INC. 2018: S90
View details for Web of Science ID 000431188500527
Enhancer connectome functionally interrogates GWAS-identified intergenic SNPs associated with inflammatory skin conditions Jeng, M. Y., Mumbach, M. R., Granja, J. M., Satpathy, A. T., Chang, H., Chang, A. ELSEVIER SCIENCE INC. 2018: S140
View details for Web of Science ID 000431498600086
Differences in skin aging characteristics in women of East Asian versus European descent residing in the same geographic location Guan, L., Zhu, G. A., Li, S., Montana, M., Kern, D., Knaggs, H. E., Chang, A. ELSEVIER SCIENCE INC. 2018: S216
View details for Web of Science ID 000431498600533
Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility Cho, H., Kuo, K., Li, S., Bailey-Healy, I., Aasi, S., Chang, A., Oro, A. E., Epstein, E., Tang, J., Sarin, K. Y. ELSEVIER SCIENCE INC. 2018: S28
View details for Web of Science ID 000431188500164
Adjuvant radiotherapy following resection for non-melanoma skin cancer: A retrospective analysis of recurrence risk at Stanford Cannon, J. D., Li, S., Hara, W., Chang, A. ELSEVIER SCIENCE INC. 2018: S93
View details for Web of Science ID 000431188500545
An exploratory open- label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Tran, D., Moffat, A., Brotherton, R., Pague, A., Zhu, G., Chang, A. S. 2018; 78 (5): 1011?13
View details for PubMedID 29175429
Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator-initiated trial. Journal of the European Academy of Dermatology and Venereology : JEADV Cannon, J. G., Tran, D. C., Li, S., Chang, A. S. 2018
View details for PubMedID 29405443
Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study Journal of the American Academy of Dermatology Lee, C., Li, S., Tran, D., Kwong, B., Chang, A. S. 2018
View details for DOI 10.1016/j/jaad.2018.05.035
Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. Journal of the European Academy of Dermatology and Venereology : JEADV Lear, J. T., Migden, M. R., Lewis, K. D., Chang, A. L., Guminski, A., Gutzmer, R., Dirix, L., Combemale, P., Stratigos, A., Plummer, R., Castro, H., Yi, T., Mone, M., Zhou, J., Trefzer, U., Kaatz, M., Loquai, C., Kudchadkar, R., Sellami, D., Dummer, R. 2018; 32 (3): 372?81
Abstract

Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult-to-treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial.To evaluate long-term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month analyses.BOLT (NCT01327053, ClinicalTrials.gov), a double-blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI-treatment-na�ve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1�:�2 to sonidegib 200�mg (laBCC, n�=�66; mBCC, n�=�13) or 800�mg (laBCC, n�=�128; mBCC, n�=�23). Tumour response was assessed per central and investigator review.With 30�months of follow-up, among patients treated with sonidegib 200�mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1�months (central) and 15.7�months (investigator) in laBCC and 24.0�months (central) and 18.1�months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200-mg arm died. Median overall survival was not reached in either population; 2-year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non-aggressive histology. Sonidegib 200�mg continued to have a better safety profile than 800�mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%).Sonidegib continued to demonstrate long-term efficacy and safety in these populations. These data support the use of sonidegib 200�mg per local treatment guidelines.

View details for PubMedID 28846163
Evidence-based update on rosacea comorbidities and their common physiologic pathways. Journal of the American Academy of Dermatology Holmes, A. D., Spoendlin, J., Chien, A. L., Baldwin, H., Chang, A. L. 2018; 78 (1): 156?66
Abstract

Rosacea is a common chronic inflammatory disease affecting the facial skin whose etiology and pathophysiology are the subject of much investigation. Risk factors include genetic and environmental elements that may predispose individuals to localized inflammation and abnormal neurovascular responses to stimuli. Recent studies have introduced an array of systemic rosacea comorbidities, such as inflammatory bowel disease and neurologic conditions, that can be challenging to synthesize. We critically review the current data behind reported rosacea comorbidities and identify and highlight underrecognized physiologic mediators shared among rosacea and associated comorbidities. This information may be helpful in addressing patient questions about potential systemic implications of rosacea and can serve as a candidate platform for future research to understand rosacea and improve treatments.

View details for PubMedID 29089181
Emerging trends in the treatment of advanced basal cell carcinoma. Cancer treatment reviews Migden, M. R., Chang, A. L., Dirix, L., Stratigos, A. J., Lear, J. T. 2018; 64: 1?10
Abstract

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.

View details for PubMedID 29407368
Pembrolizumab for advanced basal cell carcinoma: an investigator-initiated, proof-of-concept study. Journal of the American Academy of Dermatology Chang, A. L., Tran, D. C., Cannon, J. G., Li, S., Jeng, M., Patel, R., Van der Bokke, L., Pague, A., Brotherton, R., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S., Sarin, K., Colevas, A. D. 2018
View details for PubMedID 30145186
Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility Journal of Clinical Investigation Insight Cho, H. G., Kuo, K. Y., Li, S., Bailey, I., Aasi, S., Chang, A. S., Oro, A., Epstein, E., Tang, J., Sarin, K. 2018; Accepted
A case of metastatic basal cell carcinoma treated with continuous PD-1 inhibitor exposure even after subsequent initiation of radiotherapy and surgery. JAAD case reports Cannon, J. G., Russell, J. S., Kim, J., Chang, A. L. 2018; 4 (3): 248?50
View details for PubMedID 29687062

View details for PubMedCentralID PMC5909484
PD-1 blockade with cemiplimab in advanced squamous cell carcinoma New England Journal of Medicine Migden, M. R., Rischin, D., Schmults, C. D., Guminski, A., Hauschild, A., Lewis, K., Chung, C. H., Hernandez-Aya, L., Lim, A., Chang, A. S., et al 2018
View details for DOI 10.1056/NEJMoa1805131
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. The New England journal of medicine Migden, M. R., Rischin, D., Schmults, C. D., Guminski, A., Hauschild, A., Lewis, K. D., Chung, C. H., Hernandez-Aya, L., Lim, A. M., Chang, A. L., Rabinowits, G., Thai, A. A., Dunn, L. A., Hughes, B. G., Khushalani, N. I., Modi, B., Schadendorf, D., Gao, B., Seebach, F., Li, S., Li, J., Mathias, M., Booth, J., Mohan, K., Stankevich, E., Babiker, H. M., Brana, I., Gil-Martin, M., Homsi, J., Johnson, M. L., Moreno, V., Niu, J., Owonikoko, T. K., Papadopoulos, K. P., Yancopoulos, G. D., Lowy, I., Fury, M. G. 2018
Abstract

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 .).

View details for PubMedID 29863979
A daily skincare regimen with a unique ceramide and filaggrin formulation rapidly improves chronic xerosis, pruritus, and quality of life in older adults GERIATRIC NURSING Chang, A. S., Chen, S. C., Osterberg, L., Brandt, S., von Grote, E. C., Meckfessel, M. H. 2018; 39 (1): 24?28
Abstract

A skin care regimen which significantly improved atopic dermatitis and pruritus was evaluated for its efficacy and acceptability in senior subjects diagnosed with xerosis who also suffer from pruritus. This was an open-label, single-center study, designed to evaluate the daily use of a skin care regimen for 15 days. Assessments were made at baseline, day 8 and day 15 for visual skin dryness, transepidermal water loss (TEWL), hydration, desquamation, subject-perceived itch and quality of life (QoL). Twenty-five subjects, ages 60-73 years, had significantly improved skin visual dryness, hydration, desquamation, itch and QoL at days 8 and 15, relative to baseline (P�<�.05). TEWL was improved, though not significantly. Subjects expressed a high degree of satisfaction with the results. This regimen provides geriatric patients with an easily incorporated skin routine to help improve a common symptom of aging skin which negatively affects QoL.

View details for PubMedID 28600081
Commentary on Development of Basal Cell Carcinoma With Squamous Differentiation During Vismodegib Treatment DERMATOLOGIC SURGERY Chang, A. S. 2017; 43 (7): 991?92
View details for PubMedID 28640761
An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic center Duy Tran, Li, S., Henry, S., Wood, D., Chang, A. MOSBY-ELSEVIER. 2017: AB39
View details for Web of Science ID 000403369300150
PD-1 inhibition for cutaneous squamous cell carcinoma: A study of six consecutive cases Duy Tran, Colevas, A., Chang, A. MOSBY-ELSEVIER. 2017: AB193
View details for Web of Science ID 000403369301360
A randomized, double-blind, placebo-controlled crossover trial of levocarnitine for vismodegib-associated muscle spasms (NCT1893892) Cannon, J. D., Tran, D. C., Li, S., Chang, A. S. ELSEVIER SCIENCE INC. 2017: S51
View details for DOI 10.1016/j.jid.2017.02.318

View details for Web of Science ID 000406862400301
Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities. JAMA dermatology Chang, J., Zhu, G. A., Cheung, C., Li, S., Kim, J., Chang, A. L. 2017
Abstract

Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.To assess PD-L1 expression in treatment-naive and treated BCCs.This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P?=?.003) and TILs (47% vs 18%, P?=?.008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P?=?.007).Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.

View details for DOI 10.1001/jamadermatol.2016.5062

View details for PubMedID 28259105
Node-positive cutaneous squamous cell carcinoma of the head and neck: Survival, high-risk features, and adjuvant chemoradiotherapy outcomes. Head & neck Amoils, M., Lee, C. S., Sunwoo, J., Aasi, S. Z., Hara, W., Kim, J., Sirjani, D., Colevas, A. D., Chang, A. L., Divi, V. 2017
Abstract

Data lacks to guide treatment of regionally metastatic cutaneous head and neck squamous cell carcinoma (HNSCC).We conducted a retrospective review of 80 patients treated for regionally metastatic cutaneous HNSCC. The effect of various clinicopathologic variables on overall survival (OS) was investigated, in addition to outcomes by treatment modality.On multivariate regression, cutaneous primary >2 cm (p = .03) and extracapsular spread (ECS; p = .01) were significantly associated with decreased OS. Location of regional metastasis (neck vs parotid vs both) had no effect on OS (p = .2), nor did the presence of a cutaneous primary at the time of presentation (p = .9). The 3-year survival was 43%, 52%, and 49% for surgery alone, adjuvant radiation, and adjuvant chemoradiation, respectively. Fifty-one percent of patients had a recurrence of their disease.Regionally metastatic cutaneous HNSCC is an aggressive disease associated with high recurrence rates. Patients with tumors >2 cm and ECS have poorer OS despite adjuvant therapy. � 2017 Wiley Periodicals, Inc. Head Neck 39: 881-885, 2017.

View details for DOI 10.1002/hed.24692

View details for PubMedID 28252823
Elder mistreatment training gaps among dermatology resident physicians and opportunity to improve care of a vulnerable population: A cross-sectional study. Journal of the American Academy of Dermatology Danesh, M., Chang, J., Millsop, J. W., Saric, S., Li, S., Chang, A. L. 2017; 76 (2): 360-362
View details for DOI 10.1016/j.jaad.2016.08.058

View details for PubMedID 28089004
An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic center British Journal of Dermatology Tran, D. C., Li, S., Henry, S., Wood, D., Chang, A. 2017: 1749?51
View details for DOI 10.1111/bjd.15225

View details for PubMedCentralID PMC5813161
Reversible cutaneous side effects of vismodegib treatment. Cutis Kwong, B., Danial, C., Liu, A., Chun, K. A., Chang, A. L. 2017; 99 (3): E19?E20
View details for PubMedID 28398426
Cross-modal Attribute Transfer for Rescaling 3D Models Shao, L., Chang, A. X., Su, H., Savva, M., Guibas, L., IEEE IEEE. 2017: 640?48
View details for DOI 10.1109/3DV.2017.00078

View details for Web of Science ID 000454981700068
An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic centre. The British journal of dermatology Tran, D. C., Li, S., Henry, S., Wood, D. J., Chang, A. L. 2017; 177 (6): 1749?51
View details for PubMedID 27943239
Emerging trends in the treatment of advanced basal cell carcinoma Cancer Treatment Reviews Migden, M., Chang, A., Dirix, L., Stratigos, A., Lear, J. T. 2017: 1?10
Abstract

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.

View details for DOI 10.1016/j.ctrv.2017.12.009
Evidence-based update on rosacea comorbidities and their common physiologic pathways Journal of the American Academy of Dermatology Holmes, A., Chien, A., Baldwin, H., Spoendlin, J., Chang, A. S. 2017; October: 156?66
Abstract

Rosacea is a common chronic inflammatory disease affecting the facial skin whose etiology and pathophysiology are the subject of much investigation. Risk factors include genetic and environmental elements that may predispose individuals to localized inflammation and abnormal neurovascular responses to stimuli. Recent studies have introduced an array of systemic rosacea comorbidities, such as inflammatory bowel disease and neurologic conditions, that can be challenging to synthesize. We critically review the current data behind reported rosacea comorbidities and identify and highlight underrecognized physiologic mediators shared among rosacea and associated comorbidities. This information may be helpful in addressing patient questions about potential systemic implications of rosacea and can serve as a candidate platform for future research to understand rosacea and improve treatments.

View details for DOI 10.1016/j.jaad.2017.07.055
Elder mistreatment training gaps among dermatology resident physicians and opportunity to improve care of a vulnerable population: A cross -sectional study Journal of the American Academy of Dermatology Danesh, M., Chang, J., Millsop, J. W., Saric, S., Li, S., Chang, A. 2017; 76 (2): 360-362
Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma. The British journal of dermatology Chang, J., Tran, D. C., Zhu, G. A., Li, R., Whitson, R., Kim, Y. H., Gupta, A., Afshari, A., Antes, T., Spitale, R. C., Chang, A. L. 2017; 177 (5): e187?e190
View details for PubMedID 28369780
Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study J Eur Acad Dermatol Venereol. Lear, J., Migden, M., Chang, A. S., et al 2017: 372?81
Abstract

Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult-to-treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial.To evaluate long-term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month analyses.BOLT (NCT01327053, ClinicalTrials.gov), a double-blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI-treatment-na�ve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1�:�2 to sonidegib 200�mg (laBCC, n�=�66; mBCC, n�=�13) or 800�mg (laBCC, n�=�128; mBCC, n�=�23). Tumour response was assessed per central and investigator review.With 30�months of follow-up, among patients treated with sonidegib 200�mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1�months (central) and 15.7�months (investigator) in laBCC and 24.0�months (central) and 18.1�months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200-mg arm died. Median overall survival was not reached in either population; 2-year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non-aggressive histology. Sonidegib 200�mg continued to have a better safety profile than 800�mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%).Sonidegib continued to demonstrate long-term efficacy and safety in these populations. These data support the use of sonidegib 200�mg per local treatment guidelines.

View details for DOI 10.1111/jdv.14542

View details for PubMedCentralID PMC5873455
Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma British Journal of Dermatology Chang, D. J., et al 2017; March: e187?e190
View details for DOI 10.1111/bjd.15508
Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing PLOS ONE Xu, J., Spitale, R. C., Guan, L., Flynn, R. A., Torre, E. A., Li, R., Reber, I., Qu, K., Kern, D., Knaggs, H. E., Chang, H. Y., Chang, A. L. 2016; 11 (11)
Abstract

While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. The main objective of this study was to perform an unbiased, whole transcriptome search for genes that associate with intrinsic skin youthfulness. To accomplish this, healthy women (n = 122) of European descent, ages 18-89 years with Fitzpatrick skin type I/II were examined for facial skin aging parameters and clinical covariates, including smoking and ultraviolet exposure. Skin youthfulness was defined as the top 10% of individuals whose assessed skin aging features were most discrepant with their chronological ages. Skin biopsies from sun-protected inner arm were subjected to 3'-end sequencing for expression quantification, with results verified by quantitative reverse transcriptase-polymerase chain reaction. Unbiased clustering revealed gene expression signatures characteristic of older women with skin youthfulness (n = 12) compared to older women without skin youthfulness (n = 33), after accounting for gene expression changes associated with chronological age alone. Gene set analysis was performed using Genomica open-access software. This study identified a novel set of candidate skin youthfulness genes demonstrating differences between SY and non-SY group, including pleckstrin homology like domain family A member 1 (PHLDA1) (p = 2.4x10-5), a follicle stem cell marker, and hyaluronan synthase 2-anti-sense 1 (HAS2-AS1) (p = 0.00105), a non-coding RNA that is part of the hyaluronan synthesis pathway. We show that immunologic gene sets are the most significantly altered in skin youthfulness (with the most significant gene set p = 2.4x10-5), suggesting the immune system plays an important role in skin youthfulness, a finding that has not previously been recognized. These results are a valuable resource from which multiple future studies may be undertaken to better understand the mechanisms that promote skin youthfulness in humans.

View details for DOI 10.1371/journal.pone.0165913

View details for Web of Science ID 000387724300066

View details for PubMedCentralID PMC5102383
Follow-up on Programmed Cell Death 1 Inhibitor for Cutaneous Squamous Cell Carcinoma. JAMA dermatology Tran, D. C., Colevas, A. D., Chang, A. L. 2016
View details for DOI 10.1001/jamadermatol.2016.3884

View details for PubMedID 27784038
Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma: Not a Case-Control Study Reply JAMA DERMATOLOGY Li, S., Chang, A. S. 2016; 152 (10): 1173
View details for PubMedID 27732729
Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials ORPHANET JOURNAL OF RARE DISEASES Chang, A. S., Arron, S. T., Migden, M. R., Solomon, J. A., Yoo, S., Day, B., McKenna, E. F., Sekulic, A. 2016; 11: 120
Abstract

Aberrant activation of the Hedgehog (Hh) pathway is a key driver in the pathogenesis of basal cell carcinomas (BCCs), including patients with BCC nevus syndrome (BCCNS). It is unclear whether BCCs arising in patients with BCCNS respond differently to vismodegib than in patients without BCCNS. We examined the best overall response rate (BORR) and adverse events (AEs) of vismodegib in patients with advanced BCC (aBCC) with and without BCCNS.Patients were treated with vismodegib 150�mg/day in the ERIVANCE BCC trial (ClinicalTrials.gov number, NCT00833417) and the expanded access study (EAS; ClinicalTrials.gov number, NCT01160250). BCCNS diagnosis was based on medical history at the time of enrollment. Metastatic BCC response was evaluated using Response Evaluation Criteria In Solid Tumors, version 1.0 (RECIST v1.0) in both studies. Locally advanced BCC was evaluated by a novel composite end point in ERIVANCE BCC and by RECIST v1.0 in the EAS. Response assessments were performed every 8�weeks in ERIVANCE BCC and every 8-16 weeks in the EAS. Safety assessments (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) were performed monthly in both trials. Because of described differences in response assessment/schedule, patients with BCCNS were not pooled across trials. Analytic cohorts for BCCNS and sporadic aBCC were created within each trial for comparison using descriptive statistical methods.Forty-one patients with BCCNS were included in the study: 22 from ERIVANCE BCC and 19 from the EAS. Investigator-assessed BORR in BCCNS groups ranged from 31 to 81�% in patients with locally advanced BCC (n?=?33) and was 50�% in patients with metastatic BCC (n?=?6). These results were comparable with the non-BCCNS groups. Incidence and severity of AEs were also comparable between the BCCNS and non-BCCNS groups. Amenorrhea was observed in both patient cohorts and was reversible in two patients who discontinued treatment.Vismodegib demonstrated comparable efficacy and safety against aBCC in patients with and without BCCNS.

View details for PubMedID 27581207
Investigator-assessed efficacy and safety of sonidegib in patients with locally advanced basal cell carcinoma and metastatic basal cell carcinoma: results of the BOLT 30-month analysis Dummer, R., Migden, M., Guminski, A., Gutzmer, R., Kudchadkar, R., Lewis, K., Dirix, L., Combemale, P., Trefzer, U., Loquai, C., Kaatz, M., Chang, A. L., Stratigos, A., Plummer, R., Mone, M., Castro, H., Yi, T., Sellami, D., Lear, J. LIPPINCOTT WILLIAMS & WILKINS. 2016: E3
View details for Web of Science ID 000383560800005
Male gender is a significant risk factor for the development of multiple basal cell cancers Batra, P., Kuo, K., Chahal, H. S., Rieger, K., Oro, A. E., Chang, A. S., Li, S., Tang, J., Sarin, K. ELSEVIER SCIENCE INC. 2016: B5
View details for DOI 10.1016/j.jid.2016.05.023

View details for Web of Science ID 000380585200020
Sonidegib safety in patients with locally advanced Basal Cell Carcinoma and efficacy based on tumor aggressiveness Lear, J., Guminski, A., Gutzmer, R., Migden, M., Kudchadkar, R., Lewis, K., Dirix, L., Plummer, R., Stratigos, A., Chang, A. L., Trefzer, U., Loquai, C., Kaatz, M., Combemale, P., Mone, M., Castro, H., Yi, T., Sellami, D., Dummer, R. LIPPINCOTT WILLIAMS & WILKINS. 2016: E72?E73
View details for Web of Science ID 000383560800137
Update to an open-label clinical trial of vismodegib as neoadjuvant before surgery for high-risk basal cell carcinoma (BCC) JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Kwon, G. P., Ally, M., Bailey-Healy, I., Oro, A. E., Kim, J., Chang, A., Aasi, S., Tang, J. Y. 2016; 75 (1): 213?15
View details for PubMedID 27317518
The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Dummer, R., Guminski, A., Gutzmer, R., Dirix, L., Lewis, K. D., Combemale, P., Herd, R. M., Kaatz, M., Loquai, C., Stratigos, A. J., Schulze, H., Plummer, R., Gogov, S., Pallaud, C., Yi, T., Mone, M., Chang, A. S., Cornelis, F., Kudchadkar, R., Trefzer, U., Lear, J. T., Sellami, D., Migden, M. R. 2016; 75 (1): 113-+
Abstract

The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.This report provides long-term follow-up data collected up to 12�months after the last patient was randomized.In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800�mg. The primary end point was objective response rate assessed by central review.Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6�months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800�mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.

View details for PubMedID 27067394
Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma JAMA DERMATOLOGY Mohan, S. V., Chang, J., Li, S., Henry, A. S., Wood, D. J., Chang, A. L. 2016; 152 (5): 527-532
Abstract

Smoothened inhibitors (SIs) are a new type of targeted therapy for advanced basal cell carcinoma (BCC), and their long-term effects, such as increased risk of subsequent malignancy, are still being explored.To evaluate the risk of developing a non-BCC malignancy after SI exposure in patients with BCC.A case-control study at Stanford Medical Center, an academic hospital. Participants were higher-risk patients with BCC diagnosed from January 1, 1998, to December 31, 2014. The dates of the analysis were January 1 to November 1, 2015.The exposed participants (cases) comprised patients who had confirmed prior vismodegib treatment, and the nonexposed participants (controls) comprised patients who had never received any SI. Because vismodegib was the first approved SI, only patients exposed to this SI were included.Hazard ratio for non-BCC malignancies after vismodegib exposure, adjusting for covariates.The study cohort comprised 180 participants. Their mean (SD) age at BCC diagnosis was 56 (16) years, and 68.9% (n?=?124) were male. Fifty-five cases were compared with 125 controls, accounting for age, sex, prior radiation therapy or cisplatin treatment, Charlson Comorbidity Index, clinical follow-up time, immunosuppression, and basal cell nevus syndrome status. Patients exposed to vismodegib had a hazard ratio of 6.37 (95% CI, 3.39-11.96; P?
View details for DOI 10.1001/jamadermatol.2015.4330

View details for PubMedID 26914338
PDL1 and CD8 expression in basal cell carcinoma correlates with response to Hedgehog inhibitor therapy Chang, J., Zhu, G. A., Li, S., Kim, J., Chang, A. S. ELSEVIER SCIENCE INC. 2016: S44
View details for DOI 10.1016/j.jid.2016.02.279

View details for Web of Science ID 000380028800250
Dermatology resident physician training and readiness to identify and manage elder mistreatment Chang, J., Danesh, M., Endo, J., Osterberg, L., Millsop, J., Aughenbaugh, W., Schillinger, E., Singh, B., Sussman, R., Chang, A. S. MOSBY-ELSEVIER. 2016: AB25
View details for Web of Science ID 000412760201016
Identification of metastasis-associated microRNAs in basal cell carcinoma Chang, J., Zhu, G. A., Li, R., Antes, T., Spitale, R., Chang, A. S. MOSBY-ELSEVIER. 2016: AB199
View details for Web of Science ID 000412760201660
Expanding Our Understanding of Human Skin Aging JOURNAL OF INVESTIGATIVE DERMATOLOGY Chang, A. S. 2016; 136 (5): 897?99
Abstract

Two very different studies expand our understanding of human skin aging. In the first study, H�ls et�al. show an association between nitrogen dioxide levels in outdoor air and number of lentigines on the cheek. In the second study, Bowman and Birch-Machin show that mitochondrial complex II activity in human skin fibroblasts decreases with age.

View details for PubMedID 27107374
Dermatology resident physician training and readiness to identify and manage elder mistreatment Chang, J., Danesh, M., Hibler, B., Saric, S., Millsop, J., Endo, J., Aughenbaugh, W., Chang, A. S. ELSEVIER SCIENCE INC. 2016: S27
View details for DOI 10.1016/j.jid.2016.02.180

View details for Web of Science ID 000380028800153
Increased risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma Chang, A. S., Mohan, S., Chang, J., Wood, D., Henry, S., Li, S. ELSEVIER SCIENCE INC. 2016: S28
View details for DOI 10.1016/j.jid.2016.02.183

View details for Web of Science ID 000380028800156
Efficacy and safety of sonidegib in patients (pts) with nevoid basal cell carcinoma syndrome (NBCCS) Lear, J., Migden, M., Guminski, A., Dirix, L., Chang, A. S., Burnett, P., Sellami, D., Gutzmer, R., Stingl, G., Dummer, R. MOSBY-ELSEVIER. 2016: AB196
View details for Web of Science ID 000412760201652
Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma. JAMA dermatology Ally, M. S., Ransohoff, K., Sarin, K., Atwood, S. X., Rezaee, M., Bailey-Healy, I., Kim, J., Beachy, P. A., Chang, A. L., Oro, A., Tang, J. Y., Colevas, A. D. 2016; 152 (4): 452-456
Abstract

Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors.To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples.Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015.The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability.Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P?
View details for DOI 10.1001/jamadermatol.2015.5473

View details for PubMedID 26765315
An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib CLINICAL CANCER RESEARCH Danial, C., Sarin, K. Y., Oro, A. E., Chang, A. L. 2016; 22 (6): 1325-1329
Abstract

To assess the tumor response to the smoothened (SMO) inhibitor, sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) resistant to treatment with vismodegib (GDC0449).Nine patients with an advanced BCC that was previously resistant to treatment with vismodegib were given sonidegib in this investigational, open-label study. Tumor response was determined using the response evaluation criteria in solid tumors. SMO mutations were identified using biopsy samples from the target BCC location.The median duration of treatment with sonidegib was 6 weeks (range, 3-58 weeks). Five patients experienced progressive disease with sonidegib. Three patients experienced stable disease and discontinued sonidegib either due to adverse events (n = 1) or due to election for surgery (n = 2). The response of one patient was not evaluable. SMO mutations with in vitro data suggesting resistance to Hh pathway inhibition were identified in 5 patients, and none of these patients experienced responses while on sonidegib.Patients with advanced BCCs that were previously resistant to treatment with vismodegib similarly demonstrated treatment resistance with sonidegib. Patients who have developed treatment resistance to an SMO inhibitor may continue to experience tumor progression in response to other SMO inhibitors. Clin Cancer Res; 22(6); 1325-9. �2015 AACR.

View details for DOI 10.1158/1078-0432.CCR-15-1588

View details for Web of Science ID 000373358900006

View details for PubMedID 26546616

View details for PubMedCentralID PMC4794361
Regionally Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck: Survival and High-Risk Features Amoils, M., Lee, C. S., Sunwoo, J., Aasi, S. Z., Hara, W., Kim, J., Sirjani, D., Colevas, A. D., Chang, A. S., Divi, V. ELSEVIER SCIENCE INC. 2016: 954
View details for DOI 10.1016/j.ijrobp.2015.12.304

View details for Web of Science ID 000371581900251
Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool. BMC dermatology Zhu, G. A., Raber, I., Sakshuwong, S., Li, S., Li, A. S., Tan, C., Chang, A. L. 2016; 16 (1): 1-?
Abstract

Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability.A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample.1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n?=?149) and controls (n?=?298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p?=?0.003) and (2) less engagement in UV protective behaviors (p?
View details for DOI 10.1186/s12895-016-0038-1

View details for PubMedID 26790927

View details for PubMedCentralID PMC4721109
Safety and efficacy of vismodegib in patients aged ?65 years with advanced basal cell carcinoma. Oncotarget Chang, A. L., Lewis, K. D., Arron, S. T., Migden, M. R., Solomon, J. A., Yoo, S., Day, B. M., McKenna, E. F., Sekulic, A. 2016; 7 (46): 76118?24
Abstract

Because many patients with unresectable basal cell carcinoma (BCC) are aged ?65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ?65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ?65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ?65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ?65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

View details for PubMedID 27764798
Expanding our knowledge of human skin aging Journal of Investigative Dermatology Chang, A. S. 2016; 136 (5): 897-9
View details for DOI 10.1016/j.jid.2016.02.020.
Novel Gene expression Profile of Women with Intrinsic Skin Youthfulness By Whole Transcriptome Sequencing PLoS ONE Xu, J., Spitale, R., Guan, L., Flynn, R. A., Torre, E., Li, R., Raber, I., Qu, K., Kern, D., Knaggs, H. E., Chang, H. Y., Chang, A. S. 2016; 11 (11): e0165913
View details for DOI 10.1371/journal.pone.0165913
Invited Commentary on "Dermatological disease in the older age group" in British Medical Journal Open 2015 Dec 23;5(12)e009941 Practice Updates Chang, A. S. 2016
Update to an open-label clinical trial of vismodegib as neoadjuvant before surgery for high-risk basal cell carcinoma (BCC) Journal of the American Academy of Dermatology Kwon, G. P., Ally, M., Bailey-Healy, I., Oro, A. E., Kim, J., Chang, A. S., Aasi, S., Tang, J. Y. 2016; 75 (1): 213-15
Follow-up on Programmed Cell Death 1 Inhibitor for Cutaneous Squamous Cell Carcinoma JAMA Dermatology Tran, D. C., Colevas, A. D., Chang, A. S. 2016; 153 (1): 92-94
Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials Orphanet Journal of Rare Diseases Chang, A. S., Arron, S., Migden, M., Solomon, J. A., Yoo, S., Day, B., McKenna, E. F., Sekulic, A. 2016; 11 (120)
The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. Journal of the American Academy fo Dermatology Dummer, R., Guminski, A., Gutzmer, R., Dirix, L., Lewis, K. D., Combemale, P., Herd, R., Kaatz, M., Loquai, C., Stratigos, A. J., Schulze, H., Plummer, R., Gogov, S., Pallaud, C., Yi, T., Mone, M., Chang, A. S., Cornelis, F., Kudchadkar, R., Trefzer, U., Lear, J., Sellami, D., Migden, M. 2016
View details for DOI 10.1016/j.jaad.2016.02.1226. Epub 2016 Apr 7.
Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma Journal of the American Academy of Dermatology Case Reports Mohan, S., Kuo, K. Y., Chang, A. S. 2016
View details for DOI 10.1016/j.jdcr.2015.11.007
Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma. JAAD case reports Mohan, S. V., Kuo, K. Y., Chang, A. L. 2016; 2 (1): 13-15
View details for DOI 10.1016/j.jdcr.2015.11.007

View details for PubMedID 27051815

View details for PubMedCentralID PMC4809440
Effects of combined treatment with arsenic trioxide and itraconazole in patients with refractory metastatic basal cell carcinoma JAMA Dermatology Sarin, K. Y., Ally, M. S., Ransohoff, K. J., Atwood, S. X., Rezaee, M. 2016: 1?5
Abstract

Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors.To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples.Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015.The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability.Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P?
View details for DOI 10.1001/jamadermatol.2015.5473
Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing. PloS one Xu, J., Spitale, R. C., Guan, L., Flynn, R. A., Torre, E. A., Li, R., Raber, I., Qu, K., Kern, D., Knaggs, H. E., Chang, H. Y., Chang, A. L. 2016; 11 (11)
Abstract

While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. The main objective of this study was to perform an unbiased, whole transcriptome search for genes that associate with intrinsic skin youthfulness. To accomplish this, healthy women (n = 122) of European descent, ages 18-89 years with Fitzpatrick skin type I/II were examined for facial skin aging parameters and clinical covariates, including smoking and ultraviolet exposure. Skin youthfulness was defined as the top 10% of individuals whose assessed skin aging features were most discrepant with their chronological ages. Skin biopsies from sun-protected inner arm were subjected to 3'-end sequencing for expression quantification, with results verified by quantitative reverse transcriptase-polymerase chain reaction. Unbiased clustering revealed gene expression signatures characteristic of older women with skin youthfulness (n = 12) compared to older women without skin youthfulness (n = 33), after accounting for gene expression changes associated with chronological age alone. Gene set analysis was performed using Genomica open-access software. This study identified a novel set of candidate skin youthfulness genes demonstrating differences between SY and non-SY group, including pleckstrin homology like domain family A member 1 (PHLDA1) (p = 2.4x10-5), a follicle stem cell marker, and hyaluronan synthase 2-anti-sense 1 (HAS2-AS1) (p = 0.00105), a non-coding RNA that is part of the hyaluronan synthesis pathway. We show that immunologic gene sets are the most significantly altered in skin youthfulness (with the most significant gene set p = 2.4x10-5), suggesting the immune system plays an important role in skin youthfulness, a finding that has not previously been recognized. These results are a valuable resource from which multiple future studies may be undertaken to better understand the mechanisms that promote skin youthfulness in humans.

View details for DOI 10.1371/journal.pone.0165913

View details for PubMedID 27829007
Safety and efficacy of vismodegib in patients aged >=65 years with advanced basal cell carcinoma OncoTarget Chang, A. S., Lewis, K. D., Arron, S. T., Migden, M., Solomon, J., Yoo, S., McKenna, E. F., Sekulic, A. 2016: 76118?24
Abstract

Because many patients with unresectable basal cell carcinoma (BCC) are aged ?65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ?65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ?65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ?65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ?65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

View details for DOI 10.18632/oncotarget.12660

View details for PubMedCentralID PMC5342800
Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool BioMed Central Dermatology Zhu, G. A., Raber, I., Sakshuwong, S., Li, A., Tan, C., Chang, A. S. 2016: 1
Abstract

Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability.A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample.1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n?=?149) and controls (n?=?298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p?=?0.003) and (2) less engagement in UV protective behaviors (p?
View details for DOI 10.1186/s12895-016-0038-1

View details for PubMedCentralID PMC4721109
Mutations in the Kinetochore Gene KNSTRN in Basal Cell Carcinoma. journal of investigative dermatology Jaju, P. D., Nguyen, C. B., Mah, A. M., Atwood, S. X., Li, J., Zia, A., Chang, A. L., Oro, A. E., Tang, J. Y., Lee, C. S., Sarin, K. Y. 2015; 135 (12): 3197-3200
View details for DOI 10.1038/jid.2015.339

View details for PubMedID 26348826
IMPROVEMENT OF SIGNS OF XEROSIS AND PRURITUS IN ELDERLY SUBJECTS USING A SKINCARE REGIMEN FORMULATED WITH FILAGGRIN AND CERAMIDE TECHNOLOGY Brandt, S., Chang, A. S., Meckfessel, M. OXFORD UNIV PRESS INC. 2015: 471
View details for Web of Science ID 000374222702315
RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors. Cancer research Zhao, X., Ponomaryov, T., Ornell, K. J., Zhou, P., Dabral, S. K., Pak, E., Li, W., Atwood, S. X., Whitson, R. J., Chang, A. L., Li, J., Oro, A. E., Chan, J. A., Kelleher, J. F., Segal, R. A. 2015; 75 (17): 3623-3635
Abstract

Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly understood. Using new medulloblastoma models, we identify two distinct paradigms of resistance to Smo inhibition. Sufu mutations lead to maintenance of the Shh pathway in the presence of Smo inhibitors. Alternatively activation of the RAS-MAPK pathway circumvents Shh pathway dependency, drives tumor growth, and enhances metastatic behavior. Strikingly, in BCC patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent BCC tumors. Together, these findings reveal a critical role of the RAS-MAPK pathway in drug resistance and tumor evolution of Shh pathway-dependent tumors. Cancer Res; 75(17); 3623-35. �2015 AACR.

View details for DOI 10.1158/0008-5472.CAN-14-2999-T

View details for PubMedID 26130651
A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma. Dermatology and therapy Steenrod, A. W., Smyth, E. N., Bush, E. N., Chang, A. L., Arron, S. T., Helfrich, Y. R., Von Hoff, D. D., Brail, L. H., Coyne, K. S. 2015; 5 (3): 183-199
Abstract

Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients' perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients.This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of superficial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying 'open-ended' questions and probing techniques intended to elicit patients' own description of their experiences with BCC. Telephone interviews lasted between 60 and 90�mins.Thirty-four interviews were conducted (G1: N�=�13; G2: N�=�21). The majority of patients were aged either 55-64�years (32%, N�=�11) or 76+ years (32%, N�=�11) and were primarily male (82%, N�=�28); most (75%, N�=�24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N�=�14) and cancer-related stress (41%, N�=�14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N�=�16) or emotional well-being (71%, N�=�15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N�=�4; G2: 48%, N�=�10).Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective.Eli Lilly and Company.

View details for DOI 10.1007/s13555-015-0081-6

View details for PubMedID 26324194

View details for PubMedCentralID PMC4580654
Concurrent Vismodegib and Radiotherapy for Recurrent, Advanced Basal Cell Carcinoma. JAMA dermatology Pollom, E. L., Bui, T. T., Chang, A. L., Colevas, A. D., Hara, W. Y. 2015; 151 (9): 998-1001
Abstract

Vismodegib is a targeted agent recently approved for treating patients who develop recurrent or locally advanced basal cell carcinoma (BCC), and will inevitably be integrated into existing therapy for advanced BCC as it becomes increasingly used. Improved understanding of how vismodegib interacts with other treatment modalities, including radiotherapy, would help optimize multidisciplinary therapy and clinical outcomes.We report 2 cases of recurrent, advanced BCC treated from April 1, 2012, through October 31, 2014, with concurrent radiotherapy and vismodegib. Concurrent treatment appeared to be well tolerated and efficacious, with both patients having no evidence of progressive disease at last follow-up.We found that the combination of vismodegib and radiotherapy is feasible for patients with recurrent or locally advanced BCC and that combined use of currently available therapies for advanced BCC warrants further prospective study.

View details for DOI 10.1001/jamadermatol.2015.0326

View details for PubMedID 25874733
Rolling the Genetic Dice: Neutral and Deleterious Smoothened Mutations in Drug-Resistant Basal Cell Carcinoma. journal of investigative dermatology Atwood, S. X., Sarin, K. Y., Li, J. R., Yao, C. Y., Urman, N. M., Chang, A. L., Tang, J. Y., Oro, A. E. 2015; 135 (8): 2138-2141
View details for DOI 10.1038/jid.2015.115

View details for PubMedID 25801792
Dermatology practices: Effects of geographic distribution on health care disparities Pyles, M., Nkansah-Mahaney, N., Chang, A. S., Resneck, J. NATURE PUBLISHING GROUP. 2015: S3
View details for Web of Science ID 000358272100043
The role of the dermatologist in detecting elder abuse and neglect JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Danesh, M. J., Chang, A. L. 2015; 73 (2): 285-293
Abstract

The National Research Council of the National Academies defines elder mistreatment as: (1) intentional actions that cause harm or create serious risk of harm (whether or not harm is intended) to a vulnerable elder by a caregiver or other person who stands in a trust relationship to the elder; or (2) failure by a caregiver to satisfy the elder's basic needs or to protect the elder from harm. Estimates of the prevalence of elder abuse have ranged from 2.2% to 18.4%. Dermatologists are uniquely positioned to identify and manage suspected cases of elder abuse given their expertise in distinguishing skin lesions of abuse from organic medical disease and their patient populations with strong elderly representation. This article discusses aspects of both the screening and management of elder abuse with particular relevance to dermatologists. Like physicians across medical specialties, dermatologists must be familiar with those aspects of elder abuse in screening, diagnosis, management, and reporting that are unique to their field and to those aspects that are applicable to all health care providers.

View details for DOI 10.1016/j.jaad.2015.04.006

View details for Web of Science ID 000358012900032
Overall and progression-free survival of stage 4 cutaneous squamous cell carcinoma at a single large referral center JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Zhu, G., Chang, A. 2015; 73 (1): 165?66
View details for PubMedID 26089053
Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma CLINICAL CANCER RESEARCH Mohan, S. V., Chang, A. L. 2015; 21 (12): 2677-2683
Abstract

Smoothened inhibitors represent the first class of targeted drugs approved for use in advanced and metastatic basal cell carcinoma. For many patients with limited treatment options, this drug class has led to significant clinical improvements, but is not without side effects. In this review, we outline the basic mechanism of smoothened inhibitors and the most commonly observed cutaneous and extracutaneous side effects. We also highlight possible mechanisms for these adverse events and current management strategies.

View details for DOI 10.1158/1078-0432.CCR-14-3180

View details for Web of Science ID 000357336600006
Assessment of the Genetic Basis of Rosacea by Genome-Wide Association Study JOURNAL OF INVESTIGATIVE DERMATOLOGY Chang, A. L., Raber, I., Xu, J., Li, R., Spitale, R., Chen, J., Kiefer, A. K., Tian, C., Eriksson, N. K., Hinds, D. A., Tung, J. Y. 2015; 135 (6): 1548-1555
Abstract

Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 � 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 � 10(-8) discovery group; P=4.4 � 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 � 10(-8) discovery group; P=7.2 � 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 � 10(-8) discovery group; P=7.6 � 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea.

View details for DOI 10.1038/jid.2015.53

View details for Web of Science ID 000354389200015

View details for PubMedID 25695682

View details for PubMedCentralID PMC4434179
Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Sekulic, A., Migden, M. R., Lewis, K., Hainsworth, J. D., Solomon, J. A., Yoo, S., Arron, S. T., Friedlander, P. A., Marmur, E., Rudin, C. M., Chang, A. L., Dirix, L., Hou, J., Yue, H., Hauschild, A. 2015; 72 (6): 1021-?
Abstract

Primary analysis from the pivotal ERIVANCE BCC study resulted in approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of adults with metastatic or locally advanced basal cell carcinoma (BCC) that has recurred after surgery or for patients who are not candidates for surgery or radiation.An efficacy and safety analysis was conducted 12 months after primary analysis.This was a multinational, multicenter, nonrandomized, 2-cohort study in patients with measurable and histologically confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d). Primary outcome measure was objective response rate (complete and partial responses) assessed by independent review facility.After 12 months of additional follow-up, median duration of exposure to vismodegib was 12.9 months. Objective response rate increased from 30.3% to 33.3% in patients with metastatic disease, and from 42.9% to 47.6% in patients with the locally advanced form. Median duration of response in patients with locally advanced BCC increased from 7.6 to 9.5 months. No new safety signals emerged with extended treatment duration.Limitations include low prevalence of advanced BCC and challenges of designing a study with heterogenous manifestations.The 12-month update of the study confirms the efficacy and safety of vismodegib in management of advanced BCC.

View details for DOI 10.1016/j.jaad.2015.03.021

View details for Web of Science ID 000354604200031

View details for PubMedID 25981002
Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial LANCET ONCOLOGY Migden, M. R., Guminski, A., Gutzmer, R., Dirix, L., Lewis, K. D., Combemale, P., Herd, R. M., Kudchadkar, R., Trefzer, U., Gogov, S., Pallaud, C., Yi, T., Mone, M., Kaatz, M., Loquai, C., Stratigos, A. J., Schulze, H., Plummer, R., Chang, A. S., Cornelis, F., Lear, J. T., Sellami, D., Dummer, R. 2015; 16 (6): 716?28
Abstract

Patients with advanced basal cell carcinoma have limited treatment options. Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. Patients were randomised via an automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily, stratified by disease, histological subtype, and geographical region. The primary endpoint was the proportion of patients who achieved an objective response, assessed in the primary efficacy analysis population (patients with fully assessable locally advanced disease and all those with metastatic disease) with data collected up to 6 months after randomisation of the last patient. This trial is registered with ClinicalTrials.gov, number NCT01327053.Between July 20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib group, and 151 in the 800 mg sonidegib group. Median follow-up was 13�9 months (IQR 10�1-17�3). In the primary efficacy analysis population, 20 (36%, 95% CI 24-50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116 receiving 800 mg sonidegib achieved an objective response. In the 200 mg sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective response, as assessed by central review, were noted among the 42 with locally advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally advanced disease had an objective response, as assessed by central review, as did four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200 mg group than in the 800 mg group. The most common grade 3-4 adverse events were raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.

View details for PubMedID 25981810
A new functional validation assay to measure resistance drivers in patient BCCs Annual Meeting of the Society-for-Investigative-Dermatology Whitson, R., Atwood, S., SARIN, K., Li, J., Kim, G., Rezaee, M., ALLY, M. S., Yao, C., Chang, A. S., Tang, J. Y., Oro, A. NATURE PUBLISHING GROUP. 2015: S23?S23
View details for Web of Science ID 000352783200133
Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor Vismodegib (GDC-0449) Meani, R. E., Lim, S. W., Chang, A. S., Kelly, J. W. WILEY-BLACKWELL. 2015: 53
View details for Web of Science ID 000352562300141
Lack of resistant SMO mutations and decreased mutational load of Gorlin-associated basal cell cancers explain marked response to smoothened inhibitors Sarin, K., Rezaee, M., Jaju, P., Chang, A. S., Oro, A., Epstein, E., Tang, J. Y. NATURE PUBLISHING GROUP. 2015: S23
View details for Web of Science ID 000352783200136
Combined treatment with arsenic trioxide and itraconazole inhibits the hedgehog pathway in patients with refractory metastatic basal cell carcinoma: results from a pilot trial Ransohoff, K. J., Ally, M. S., Sarin, K., Atwood, S., Rezaee, M., Bailey, I., Beachy, P., Chang, A. S., Oro, A., Colevas, D., Tang, J. Y. NATURE PUBLISHING GROUP. 2015: S30
View details for Web of Science ID 000352783200175
Rolling the genetic dice: Neutral and deleterious SMO mutations in drug-resistant basal cell carcinoma Atwood, S., Sarin, K., Li, J., Yao, C., Urman, N. M., Chang, A. S., Tang, J. Y., Oro, A. NATURE PUBLISHING GROUP. 2015: S21
View details for Web of Science ID 000352783200121
Assessment of the genetic basis of rosacea by genome-wide association study Chang, A. S., Raber, I., Xu, J., Li, R., Spitale, R., Chen, J., Kiefer, A., Tian, C., Eriksson, N., Hinds, D., Tung, J. NATURE PUBLISHING GROUP. 2015: S42
View details for Web of Science ID 000352783200245
Identification of a unique gene expression profile in older women with youthful skin Chang, A., Spitale, R., Torre, E., Li, R., Kern, D., Knaggs, H., Xu, J. MOSBY-ELSEVIER. 2015: AB24
View details for Web of Science ID 000360942900095
Hyaluronan synthase 2 antisense transcript level associates with human skin youthfulness as identified by transcriptome sequencing Xu, J., Flynn, R. A., Spitale, R., Torre, E., Li, R., Kern, D. G., Knaggs, H., Chang, H., Chang, A. S. NATURE PUBLISHING GROUP. 2015: S45
View details for Web of Science ID 000352783200266
Smoothened variants explain the majority of drug resistance in Basal cell carcinoma. Cancer cell Atwood, S. X., Sarin, K. Y., Whitson, R. J., Li, J. R., Kim, G., Rezaee, M., Ally, M. S., Kim, J., Yao, C., Chang, A. L., Oro, A. E., Tang, J. Y. 2015; 27 (3): 342-353
Abstract

Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to�aPKC-?/? or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.

View details for DOI 10.1016/j.ccell.2015.02.002

View details for PubMedID 25759020
Novel GATA6 Mutations in Patients with Pancreatic Agenesis and Congenital Heart Malformations PLOS ONE Chao, C. S., McKnight, K. D., Cox, K. L., Chang, A. S., Kim, S. K., Feldman, B. J. 2015; DOI: 10.1371/journal.pone.0118449
Novel GATA6 mutations in patients with pancreatic agenesis and congenital heart malformations. PloS one Chao, C. S., McKnight, K. D., Cox, K. L., Chang, A. L., Kim, S. K., Feldman, B. J. 2015; 10 (2)
Abstract

Patients with pancreatic agenesis are born without a pancreas, causing permanent neonatal diabetes and pancreatic enzyme insufficiency. These patients require insulin and enzyme replacement therapy to survive, grow, and maintain normal blood glucose levels. Pancreatic agenesis is an uncommon condition but high-throughput sequencing methods provide a rare opportunity to identify critical genes that are necessary for human pancreas development. Here we present the clinical history, evaluation, and the genetic and molecular analysis from two patients with pancreatic agenesis. Both patients were born with intrauterine growth restriction, minor heart defects and neonatal diabetes. In both cases, pancreatic agenesis was confirmed by imaging studies. The patients are clinically stable with pancreatic enzymes and insulin therapy. In order identify the etiology for their disease, we performed whole exome sequencing on both patients. For each proband we identified a de novo heterozygous mutation in the GATA6 gene. GATA6 is a homeobox containing transcription factor involved in both early development of the pancreas and heart. In vitro functional analysis of one of the variants revealed that the mutation creates a premature stop codon in the coding sequence resulting in the production of a truncated protein with loss of activity. These results show how genetic mutations in GATA6 may lead to functional inactivity and pancreatic agenesis in humans.

View details for DOI 10.1371/journal.pone.0118449

View details for PubMedID 25706805
Novel GATA6 Mutations in Patients with Pancreatic Agenesis and Congenital Heart Malformations. PloS one Chao, C. S., McKnight, K. D., Cox, K. L., Chang, A. L., Kim, S. K., Feldman, B. J. 2015; 10 (2): e0118449
Abstract

Patients with pancreatic agenesis are born without a pancreas, causing permanent neonatal diabetes and pancreatic enzyme insufficiency. These patients require insulin and enzyme replacement therapy to survive, grow, and maintain normal blood glucose levels. Pancreatic agenesis is an uncommon condition but high-throughput sequencing methods provide a rare opportunity to identify critical genes that are necessary for human pancreas development. Here we present the clinical history, evaluation, and the genetic and molecular analysis from two patients with pancreatic agenesis. Both patients were born with intrauterine growth restriction, minor heart defects and neonatal diabetes. In both cases, pancreatic agenesis was confirmed by imaging studies. The patients are clinically stable with pancreatic enzymes and insulin therapy. In order identify the etiology for their disease, we performed whole exome sequencing on both patients. For each proband we identified a de novo heterozygous mutation in the GATA6 gene. GATA6 is a homeobox containing transcription factor involved in both early development of the pancreas and heart. In vitro functional analysis of one of the variants revealed that the mutation creates a premature stop codon in the coding sequence resulting in the production of a truncated protein with loss of activity. These results show how genetic mutations in GATA6 may lead to functional inactivity and pancreatic agenesis in humans.

View details for DOI 10.1371/journal.pone.0118449

View details for PubMedID 25706805
Mutations in the kinetochore gene KNSTRN in basal cell carcinoma Journal of Investigative Dermatology Jaju, P., Nguyen, C., Mah, A., Atwood, S., Li, J., Zia, A., Chang, A. S., Oro, A. E., Tang, J. Y., Lee, C. S., Sarin, K. Y. 2015; TBD
View details for DOI 10.1038/jid.2015.339
A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma Dermatol Ther Steenrod, A. W., Smyth, E. N., Bush, E. N., Chang, A. L., Arron, S. T., Helfrich, Y. R., Von Hoff, D. D., Brail, L. H., Coyne, K. S. 2015; Article DigitalPreview Abstract PMID: 26324194
A case report of unresectable cutaneous squamous cell carcinoma responsive to a PD1 inhibitor JAMA Dermatology Chang, A. S., Kim, J., Sullivan-Chang, L., Luciano, R., Colevas, A. D. 2015; TBD
Recent advances in geriatric dermatology edited by Chang, A. S. Springer. 2015
Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research Mohan, S. V., Chang, A. L. 2015; 21 (12): 2677?83
Abstract

Smoothened inhibitors represent the first class of targeted drugs approved for use in advanced and metastatic basal cell carcinoma. For many patients with limited treatment options, this drug class has led to significant clinical improvements, but is not without side effects. In this review, we outline the basic mechanism of smoothened inhibitors and the most commonly observed cutaneous and extracutaneous side effects. We also highlight possible mechanisms for these adverse events and current management strategies.

View details for PubMedID 25792568
The role of the dermatologist in detecting elder abuse and neglect. Journal of the American Academy of Dermatology Danesh, M. J., Chang, A. L. 2015; 73 (2): 285?93
Abstract

The National Research Council of the National Academies defines elder mistreatment as: (1) intentional actions that cause harm or create serious risk of harm (whether or not harm is intended) to a vulnerable elder by a caregiver or other person who stands in a trust relationship to the elder; or (2) failure by a caregiver to satisfy the elder's basic needs or to protect the elder from harm. Estimates of the prevalence of elder abuse have ranged from 2.2% to 18.4%. Dermatologists are uniquely positioned to identify and manage suspected cases of elder abuse given their expertise in distinguishing skin lesions of abuse from organic medical disease and their patient populations with strong elderly representation. This article discusses aspects of both the screening and management of elder abuse with particular relevance to dermatologists. Like physicians across medical specialties, dermatologists must be familiar with those aspects of elder abuse in screening, diagnosis, management, and reporting that are unique to their field and to those aspects that are applicable to all health care providers.

View details for PubMedID 25956658
Pivotal ERIVANCE BCC study: 12-month update of efficacy and safety of vismodegib in advanced basal cell carcinoma Journal of the American Academy of Dermatology Sekulic, A., Migden, M., Lewis, K., Hainsworth, J., Solomon, J., Yoo, S., Arron, S. T., Friedlander, P. A., Marmur, E., Rudin, C., Chang, A. S., Dirix, L., Hou, J., Yue, H., Hauschild, A. 2015; 72 (6): 1021-1026
Rolling the genetic dice: neutral and deleterious Smoothened mutations in drug-resistant basal cell carcinoma Journal of Investigative Dermatology Atwood, S. X., et al 2015; doi: 10.1038/jid.2015.115
Overall and Progression-Free Survival of Stage 4 Cutaneous Squamous Cell Carcinoma at a Single Large Referral Center Journal of the American Academy of Dermatology Zhu, G. A., Chang, A. S. 2015; 73 (1): 165-166
Randomized, Double-Blind Study of Two Dosages of Sonidegib (LDE225) in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma Lancet Oncology Migden, M. R., et al 2015; http://dx.doi.org/10.1016/S1470-2045(15)70100-2
Role of the fibronectin synergy site in modulating integrin recruitment and molecular-scale force generation Chang, A. C., Mekhdjian, A. H., Morimatsu, M., Dunn, A. R. AMER SOC CELL BIOLOGY. 2014
View details for Web of Science ID 000352094103281
An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Ally, M. S., Aasi, S., Wysong, A., Teng, C., Anderson, E., Bailey-Healy, I., Oro, A., Kim, J., Chang, A. L., Tang, J. Y. 2014; 71 (5): 904-U304
Abstract

Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4�2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.Short follow-up time and no placebo control are limitations.Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

View details for DOI 10.1016/j.jaad.2014.05.020

View details for Web of Science ID 000343918200035
Two Different Scenarios of Squamous Cell Carcinoma Within Advanced Basal Cell Carcinomas Cases Illustrating the Importance of Serial Biopsy During Vismodegib Usage JAMA DERMATOLOGY Zhu, G. A., Sundram, U., Chang, A. L. 2014; 150 (9): 970-973
Abstract

IMPORTANCE Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. OBSERVATIONS The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. CONCLUSIONS AND RELEVANCE These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

View details for DOI 10.1001/jamadermatol.2014.583

View details for Web of Science ID 000345273800013
Low rate of dermatology outpatient visits in Asian-Americans: an initial survey study for associated patient-related factors BMC DERMATOLOGY Lingala, B., Li, S., Wysong, A., Truong, A. K., Kim, D., Chang, A. S. 2014; 14
View details for DOI 10.1186/1471-5945-14-13

View details for Web of Science ID 000210067500001
Patient With Gorlin Syndrome and Metastatic Basal Cell Carcinoma Refractory to Smoothened Inhibitors JAMA DERMATOLOGY Zhu, G. A., Li, A. S., Chang, A. L. 2014; 150 (8): 877-879
Abstract

IMPORTANCE Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. OBSERVATIONS A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. CONCLUSIONS AND RELEVANCE We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

View details for DOI 10.1001/jamadermatol.2013.8744

View details for Web of Science ID 000345271000014
Combined treatment with arsenic trioxide and itraconazole inhibits the Hedgehog pathway in patients with refractory metastatic basal cell carcinoma: Results from a pilot trial Rezaee, M., Ally, M. S., Sarin, K., Atwood, S., Chang, A. S., Oro, A., Bailey, I., Colevas, D., Tang, J. Y. NATURE PUBLISHING GROUP. 2014: S2
View details for Web of Science ID 000339126100045
Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC-0449) AUSTRALASIAN JOURNAL OF DERMATOLOGY Meani, R. E., Lim, S., Chang, A. L., Kelly, J. W. 2014; 55 (3): 218-221
Abstract

Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti-tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response.

View details for DOI 10.1111/ajd.12196

View details for Web of Science ID 000340406400018

View details for PubMedID 25117162
Overall and progression-free survival in metastatic basosquamous cancer: A case series. Journal of the American Academy of Dermatology Zhu, G. A., Danial, C., Liu, A., Li, S., Su Chang, A. L. 2014; 70 (6): 1145-1146
View details for DOI 10.1016/j.jaad.2014.03.003

View details for PubMedID 24831322
Precision medicine and precision therapeutics: Hedgehog signaling pathway, basal cell carcinoma and beyond. Seminars in cutaneous medicine and surgery Mohan, S. V., Chang, A. L. 2014; 33 (2): 68-71
Abstract

Precision medicine and precision therapeutics is currently in its infancy with tremendous potential to improve patient care by better identifying individuals at risk for skin cancer and predict tumor responses to treatment. This review focuses on the Hedgehog signaling pathway, its critical role in the pathogenesis of basal cell carcinoma, and the emergence of targeted treatments for advanced basal cell carcinoma. Opportunities to utilize precision medicine are outlined, such as molecular profiling to predict basal cell carcinoma response to targeted therapy and to inform therapeutic decisions.

View details for PubMedID 25085664
Only Skin Deep: Optimism and Public Self-Consciousness Did Not Associate With the Placebo Response in a Dermatology Clinical Trial JOURNAL OF DRUGS IN DERMATOLOGY Garshick, M. K., Chang, A. L., Kimball, A. B. 2014; 13 (6): 719-722
Abstract

Although not well-understood, dermatologic diseases studied in clinical trials often demonstrate substantial response to placebo. The study objective is to determine if optimism, public self-consciousness and other personality traits predict response to placebo or active treatment in a dermatology clinical trial.A questionnaire was mailed to subjects previously enrolled in a two-center rosacea study who had been randomized to either a treatment or placebo gel. The questionnaire included the Revised Life Orientation Test (LOT-R), the Public Self-Consciousness Scale, and questions to assess personality traits.Forty-seven subjects out of 83 (57%) returned the questionnaire. There was no statistically significant difference in the LOT-R score in those who responded to placebo versus those who did not (18.08 vs 17.92, P =0.92) nor in those who responded to active treatment versus those who did not (16.27 vs 15.86, P =0.79). There was no statistically sigificant difference in public-self consciousness among placebo or active treatment responders versus non-responders (11.75 vs 10.67, P =0.66; 13.55 vs 14.45, P =0.68). The placebo responders were more likely to report that they were not unusually sensitive to most drugs/medications (X2= 8.33, P =0.004).Although this pilot study is small, there was no meaningful difference in levels of optimism or public self-consciousness among those who responded to placebo. Placebo responders were more likely to report that they were not sensitive to most drugs/medications, raising the possibility that they are actually less likely to detect when they are on medications.

View details for Web of Science ID 000337552500013
Identification of unique gene expression profiles in older women with youthful appearing skin Spitale, R., Li, R., Torre, E., Kern, D. G., Knaggs, H., Chang, A. S. NATURE PUBLISHING GROUP. 2014: S135
View details for Web of Science ID 000334560400767
Unexpected complexity in smoothened variants associated with drug resistant basal cell carcinoma Sarin, K., Atwood, S., Li, J., Chang, A. S., Oro, A., Tang, J. NATURE PUBLISHING GROUP. 2014: S36
View details for Web of Science ID 000334560400207
Open-label pilot study of LDE225 in advanced basal cell carcinoma patients who have been treated previously with a non-LDE225 Smoothened inhibitor Chang, A. S., Oro, A. NATURE PUBLISHING GROUP. 2014: S101
View details for Web of Science ID 000334560400579
Identification of genes promoting skin youthfulness by genome-wide association study. journal of investigative dermatology Chang, A. L., Atzmon, G., Bergman, A., Brugmann, S., Atwood, S. X., Chang, H. Y., Barzilai, N. 2014; 134 (3): 651-657
Abstract

To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n=428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the Bonferroni threshold with Pallele<10(-8); two of these six had Pgenotype<10(-8). Quantitative trait loci mapping confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in a replication group (n=436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (Pgenotype=0.023). A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010, Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase ?-like 1) (Pgenotype=0.042). DIAPH2 has been associated with premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates with lifespan in animal models, although not humans. KCND2 is expressed in human skin, but has not been associated with aging. These genes represent new candidate genes to study the molecular basis of healthy skin aging.

View details for DOI 10.1038/jid.2013.381

View details for PubMedID 24037343
Oral smoothened inhibitor for advanced basal cell carcinoma of the hand: a case report. Hand (New York, N.Y.) Zhu, G. A., Chen, A., Chang, A. L. 2014; 9 (1): 127-128
View details for DOI 10.1007/s11552-013-9555-0

View details for PubMedID 24570650
Low rate of dermatology outpatient visits in Asian-Americans: an initial survey study for associated patient-related factors. BMC dermatology Lingala, B., Li, S., Wysong, A., Truong, A. K., Kim, D., Chang, A. L. 2014; 14 (1): 13-?
Abstract

Asian-Americans represent the fastest growing minority group in the United States, but are under-represented patients in outpatient dermatology clinics. At the same time, skin cancer rates in individuals of Asian descent are increasing, but skin cancer detection appears to be delayed in Asian-Americans compared to white individuals. Some health-care provider related factors for this phenomenon have been reported in the literature, but the patient-related factors are unclear.This exploratory study to identify patient-related factors associated with dermatology visits in Asian-Americans was performed after Institutional Review Board (IRB) approval. An anonymous, online survey utilizing validated items was conducted on adults who self-identified as Asian-American in Northern California. Univariate and multivariate logistic regression for dermatology visits as indicated by responses to the question of "ever having had skin checked by a dermatologist" were performed on survey responses pertaining to demographic information, socioeconomic factors, acculturation, knowledge of melanoma warning signs and SSE belief and practice.89.7% of individuals who opened the online survey completed the items, with 469 surveys included in the analysis. Only 60% reported ever performing a SSE, and only 48% reported ever having a skin examination by a dermatologist. Multivariate models showed that "ever performing SSE" (p?
View details for DOI 10.1186/1471-5945-14-13

View details for PubMedID 25085260
Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations. Current dermatology reports Mohan, S. V., Chang, A. L. 2014; 3: 40?45
Abstract

Advanced basal cell carcinomas are a subset of basal cell carcinomas that can be difficult to treat either due to their local invasiveness, proximity to vital structures, or metastasis. The incidence of all basal cell carcinoma is increasing in the United States, although it is not known whether advanced basal cell carcinomas (aBCCs) are also increasing. Recently, highly targeted therapy based on knowledge of the basal cell carcinoma pathogenesis has become available either commercially or through human clinical trials. These orally available drugs inhibit the Hedgehog signaling pathway, and lead to advanced basal cell carcinoma shrinkage that can enable preservation of adjacent vital organs. In this review, we outline the role of Hedgehog pathway inhibitors as well as other treatment modalities such as excision, radiotherapy and more traditional chemotherapy in treating advanced basal cell carcinomas. We also highlight current gaps in knowledge regarding the use and side effects of this targeted therapy.

View details for PubMedID 24587976

View details for PubMedCentralID PMC3931971
Dermatologic clinical trials: a practical approach Clinical dermatology trials 101: a primer for dermatologists Mohan, S., Chang, A. S. Springer. 2014; 1st: 47
View details for DOI 10.1007/978-3-319-09027-6_3
Three case reports illustrating reversible cutaneous side effects of vismodegib treatment Cutis Kwong, B., Danial, C., Liu, A., Chun, K., Chang, A. S. 2014
Low rate of dermatology outpatient visits in Asian-Americans: initial survey study for associated patient-related factors BioMed Central Dermatology Lingala, B., Wysong, A., Li, S., Truong, A., Kim, D., Chang, A. S. 2014; 14 (13)
Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chang, A. L., Solomon, J. A., Hainsworth, J. D., Goldberg, L., McKenna, E., Day, B., Chen, D. M., Weiss, G. J. 2014; 70 (1): 60-69
Abstract

Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib.We sought to assess efficacy and safety of vismodegib, while providing early drug access to patients with advanced BCC and limited treatment options.This was an open-label, multicenter study in patients with advanced BCC inappropriate for radiotherapy or surgery. Patients received 150 mg vismodegib daily until disease progression or intolerable toxicity. Tumor response was assessed via Response Evaluation Criteria in Solid Tumors version 1.0.A total of 119 patients with advanced BCC took vismodegib for a median of 5.5 months. Objective responses occurred in 46.4% of locally advanced BCC and 30.8% of patients with metastatic BCC. Response was negatively associated with prior systemic therapy in patients with locally advanced BCC (P = .002). Mean follow-up for safety was 6.5 months, with muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) as the most common adverse events.Abbreviated follow-up time because of study termination upon FDA approval was a limitation.This study provides important clinical data supporting the efficacy and safety of vismodegib. Larger studies are underway to assess predictors of response and long-term outcomes.

View details for DOI 10.1016/j.jaad.2013.09.012

View details for Web of Science ID 000328694200015

View details for PubMedID 24189279
Advanced basal cell carcinoma: epidemiology and therapeutic innovations Curr Derm Rep Mohan, S., Chang, A. S. 2014; 3 (1): 40-45
View details for DOI 10.1007/s13671-014-0069-y
Oral Smoothened Inhibitor for Advanced Basal Cell Carcinoma of the Hand: A Case Report HAND Zhu, G. A., Chen, A., Chang, A. S. 2014; 9 (1): 127-8
View details for DOI 10.1007/s11552-013-9555-0
Identification of genes promoting skin youthfulness Journal of Investigative Dermatology Chang, A. S., Atzmon, G., Bergman, A., Atwood, S., Brugmann, S., Chang, H. Y., Barzilai, N. 2014; 134 (3): 651-657
View details for DOI 10.1038/jid.2013.381
Patient With Gorlin Syndrome and Metastatic Basal Cell Carcinoma Refractory to Smoothened Inhibitors. JAMA dermatology Zhu, G. A., Li, A. S., Chang, A. L. 2014
Abstract

IMPORTANCE Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. OBSERVATIONS A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. CONCLUSIONS AND RELEVANCE We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

View details for PubMedID 24898076
Vismodegib for Periocular and Orbital Basal Cell Carcinoma JAMA OPHTHALMOLOGY Gill, H. S., Moscato, E. E., Chang, A. S., Soon, S., Silkiss, R. Z. 2013; 131 (12): 1591?94
Abstract

Basal cell carcinoma (BCC) represents 90% of malignant eyelid tumors and is locally invasive and destructive, if left untreated.To assess the feasibility of using vismodegib for periocular and orbital BCC based on its efficacy and tolerability.In this prospective observational case series, consecutive patients with periocular or orbital BCC who met criteria for treatment with vismodegib were recruited prospectively during an 8-month period from February through September 2012 from 2 academic hospitals. Seven patients received oral vismodegib, 150 mg daily, until maximum clinical response was achieved, the tumor progressed, or the patient could no longer tolerate adverse effects. Clinical response and adverse effects related to treatment were recorded. The primary endpoint was reduction in lesion size, measured as percentage change in the externally visible dimension.Oral vismodegib.All 7 patients had locally advanced, biopsy-proven, infiltrative BCC that was not amenable to surgical resection or radiation. No patients had metastatic disease at presentation. The mean patient age was 71 years (range, 43-100 years), and 4 patients (57%) had secondary orbital involvement. The mean lesion size was 3.4 cm (range, 1.0-6.0 cm), and all 7 cases (100%) represented recurrent tumors excised previously with controlled margins by frozen section or Mohs micrographic surgery. The mean treatment duration was 11 weeks (range, 4-16 weeks), and the mean duration of follow-up was 7.3 months (range, 5-10 months). Two patients (29%) demonstrated complete clinical regression, 2 (29%) demonstrated greater than 80% partial clinical regression, 2 (29%) demonstrated less than 35% partial clinical regression, and 1 (14%) progressed. Adverse reactions occurred in 6 patients (86%) and included alopecia (29%), dysgeusia (29%), muscle cramps (29%), and anorexia (14%). Two patients (29%) developed new squamous cell carcinomas (well-differentiated, keratoacanthoma type) at uninvolved sites including the eyebrow and forearm.Vismodegib seems to be well-tolerated and effective for treating periocular and orbital BCC in about half of all cases. Patients receiving treatment should be monitored for new squamous cell carcinomas at uninvolved sites.

View details for PubMedID 24136169
Markedly improved overall survival in 10 consecutive patients with metastatic basal cell carcinoma. British journal of dermatology Danial, C., Lingala, B., Balise, R., Oro, A. E., Reddy, S., Colevas, A., Chang, A. L. 2013; 169 (3): 673-676
Abstract

BACKGROUND: Metastatic basal cell carcinoma (BCC) is a rare but life-threatening condition. Prior estimates of overall survival (OS) from time of diagnosis of distant metastasis to death are approximately 8-14 months. However, these estimates are based on analyses of case reports published prior to 1984. OBJECTIVES: To assess a more updated OS in metastatic BCC patients at a single academic institution. METHODS: Using patients from 1997 to 2011, a retrospective chart review was performed on biopsy-confirmed cases of distant metastatic BCC at Stanford University School of Medicine. Kaplan-Meier analysis was used to determine OS and progression free survival (PFS). RESULTS: Ten consecutive cases of distant metastatic BCC were identified. Median OS was 7.3 (95% confidence interval, CI; 1.6, ?) years; median PFS was 3.4 (95% CI; 1.1, 5.2) years. CONCLUSION: Our findings suggest that OS in patients with distant metastaticBCC may be more favorable than previously reported.

View details for DOI 10.1111/bjd.12333

View details for PubMedID 23521172
Markedly improved overall survival in 10 consecutive patients with metastatic basal cell carcinoma BRITISH JOURNAL OF DERMATOLOGY Danial, C., Lingala, B., Balise, R., Oro, A. E., Reddy, S., Colevas, A., Chang, A. L. 2013; 169 (3): 673-676
Abstract

BACKGROUND: Metastatic basal cell carcinoma (BCC) is a rare but life-threatening condition. Prior estimates of overall survival (OS) from time of diagnosis of distant metastasis to death are approximately 8-14 months. However, these estimates are based on analyses of case reports published prior to 1984. OBJECTIVES: To assess a more updated OS in metastatic BCC patients at a single academic institution. METHODS: Using patients from 1997 to 2011, a retrospective chart review was performed on biopsy-confirmed cases of distant metastatic BCC at Stanford University School of Medicine. Kaplan-Meier analysis was used to determine OS and progression free survival (PFS). RESULTS: Ten consecutive cases of distant metastatic BCC were identified. Median OS was 7.3 (95% confidence interval, CI; 1.6, ?) years; median PFS was 3.4 (95% CI; 1.1, 5.2) years. CONCLUSION: Our findings suggest that OS in patients with distant metastaticBCC may be more favorable than previously reported.

View details for DOI 10.1111/bjd.12333

View details for Web of Science ID 000323700000027
Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced Basal cell carcinoma and resistant Basal carcinomas in gorlin syndrome. JAMA dermatology (Chicago, Ill.) Chang, A. L., Atwood, S. X., Tartar, D. M., Oro, A. E. 2013; 149 (5): 639-641
View details for DOI 10.1001/jamadermatol.2013.30

View details for PubMedID 23677114
High incidence of striae distensae in pediatric adolescent patients on high dose corticosteroids for treatment of rheumatic disease and effect on adherence to prescribed regimen Washington, N. T., Chang, A. S. NATURE PUBLISHING GROUP. 2013: S98
View details for Web of Science ID 000317698900571
Vismodegib as an adjuvant to surgery for basal cell carcinomas International Investigative Dermatology Meeting ALLY, M. S., Aasi, S., Chang, A., Teng, C., Anderson, E. M., Bailey, I., Wysong, A., Kim, J., Tang, J. Y. NATURE PUBLISHING GROUP. 2013: S178?S178
View details for Web of Science ID 000317698901336
Geriatric dermatology Part I. Geriatric pharmacology for the dermatologist JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Endo, J. O., Wong, J. W., Norman, R. A., Chang, A. L. 2013; 68 (4)
Abstract

Issues related to prescribing dermatologic drugs in the elderly are less recognized than age-related skin findings. This is related in part to the lack of a standardized residency training curriculum in geriatric dermatology. As the number of elderly patients rises in the United States, drug-related iatrogenic complications will become increasingly important. This review discusses age-related changes in pharmacokinetics and pharmacodynamics of common dermatologic drugs. These changes include volume of distribution, renal function, liver toxicity from interactions of commonly prescribed drugs, and medications that can decompensate cognition in the older patient population. We outline seven prescribing principles related to older dermatology patients, including useful strategies to reduce polypharmacy and improve drug adherence, using an evidence-based approach whenever possible.

View details for DOI 10.1016/j.jaad.2012.10.063

View details for Web of Science ID 000317201100010

View details for PubMedID 23522421
Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study JOURNAL OF INVESTIGATIVE DERMATOLOGY Chang, A. L., Bitter, P. H., Qu, K., Lin, M., Rapicavoli, N. A., Chang, H. Y. 2013; 133 (2): 394-402
Abstract

Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3'-end sequencing for expression quantification ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging"), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3'-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process.

View details for DOI 10.1038/jid.2012.287

View details for PubMedID 22931923
New Onset of Keratoacanthomas After Vismodegib Treatment for Locally Advanced Basal Cell Carcinomas: A Report of 2 Cases JAMA DERMATOLOGY Aasi, S., Silkiss, R., Tang, J. Y., Wysong, A., Liu, A., Epstein, E., Oro, A. E., Chang, A. L. 2013; 149 (2): 242-243
View details for DOI 10.1001/jamadermatol.2013.1798

View details for Web of Science ID 000317672300031

View details for PubMedID 23426496
Phase 1 Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors Cancer Clinical Research, doi:10.1158/1078-0432.CCR-12-3654 Weiss, G. J., Miller, W. H., Chang, A. S., Sharfman, W. H., Ross, R. W., Rudin, C. M. 2013; 19 (10): 2766-74
Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced basal cell carcinoma and additional resistant basal cell carcinomas in a Gorlin's syndrome patient JAMA Dermatology Chang AS, Atwood S, Tartar D, Oro AE 2013; 149 (5): 639-41
New onset of keratoacanthomas after vismodegib for locally advanced basal cell carcinomas: a report of two cases JAMA Dermatology Aasi S, Silkiss R, Tang JY, Epstein E, Wysong A, Chang AS 2013; 149 (2): 242-3
Geriatric dermatology review: Major changes in skin function in older patients and their contribution to common clinical challenges. Journal of the American Medical Directors Association Chang, A. L., Wong, J. W., Endo, J. O., Norman, R. A. 2013; 14 (10): 724?30
Abstract

There is a paucity of data to guide evidence-based treatment decisions in managing older dermatologic patients, in part because of the frequent exclusion of older adults from clinical trials. Hence, we provide a comprehensive review of important conditions in geriatric dermatology, or "dermatogeriatrics." It is our hope the field of "dermatogeriatrics" will become more evidence-based and recognized as a field in its own right so that we can better meet the needs of our growing numbers of older patients, now and in the future.

View details for PubMedID 23664020
Geriatric Dermatology. Part 2. Risk factors and cutaneous signs of elder mistreatment for the dermatologist Journal of the American Academy of Dermatology Chang AS, Wong J, Endo JO, Norman R 2013; 68 (4): 533e1-e10
Vismodegib for periocular and orbital basal cell carcinoma JAMA Ophthalmology Gill, H., Moscato, E. E., Chang, A. S., Soon, S., Silkiss, R. 2013; 131 (12): 1591-4
A simple intervention to reinforce awareness of tanning bed use and skin cancer in non-medical skin care professionals in Southern California INTERNATIONAL JOURNAL OF DERMATOLOGY Ng, A. T., Chang, A. L., Cockburn, M., Peng, D. H. 2012; 51 (11): 1307-1312
Abstract

(i) To assess the baseline knowledge of non-medical skin care professionals (estheticians, cosmetologists, massage therapists) on tanning bed use and its association with melanoma; and (ii) to provide preliminary evidence of the potential impact of a fast and simple educational intervention on tanning beds and melanoma on the awareness of non-medical skin care professionals towards skin cancer prevention.A pre-intervention survey was administered to non-medical skin care professional at salons or spas in Southern California to assess baseline knowledge on tanning and skin cancer. This was followed immediately by a 10-minute oral presentation on tanning bed use and its association with melanoma. One month later, a post-intervention survey was distributed to individuals who attended the initial oral presentation.Significant changes pre- and post-intervention were found in non-medical skin care professionals' answer responses to the following: (i) increased speaking to clients about cancer risk with tanning bed use 42-66% (OR 2.44; 95% CI 1.39, 4.30)]; (ii) decreased personal tanning bed use (23-15% [OR 0.61; 95% CI 0.37, 1.00]); and (iii) decreased belief that tanning beds are an excellent cosmetic tool (29-20% [OR 0.60; 95% CI 0.38, 0.96]).This study provides preliminary evidence that non-medical skin care professionals could be an important source of primary prevention information for reducing the burden of melanoma.

View details for DOI 10.1111/j.1365-4632.2011.05425.x

View details for Web of Science ID 000310272600006

View details for PubMedID 23067078

View details for PubMedCentralID PMC4127415
Initial Assessment of Tumor Regrowth After Vismodegib in Advanced Basal Cell Carcinoma ARCHIVES OF DERMATOLOGY Chang, A. S., Oro, A. E. 2012; 148 (11): 1324?25
View details for DOI 10.1001/archdermatol.2012.2354

View details for Web of Science ID 000311365700023

View details for PubMedID 22910979

View details for PubMedCentralID PMC3777384
Hedgehog pathway inhibition and the race against tumor evolution JOURNAL OF CELL BIOLOGY Atwood, S. X., Chang, A. L., Oro, A. E. 2012; 199 (2): 193-197
Abstract

Dependence of basal cell carcinomas and medulloblastomas on the Hedgehog pathway provides an opportunity for targeted or "personalized" therapy. The recent effectiveness and FDA approval of the first Smoothened inhibitors validates this class of agents, but has revealed drug-resistant tumor variants that bypass Smoothened inhibition. Here, we summarize the effectiveness of Hedgehog pathway inhibitors and highlight promising areas for the development of next generation drug antagonists for Hedgehog-dependent cancers.

View details for DOI 10.1083/jcb.201207140

View details for Web of Science ID 000309982400002

View details for PubMedID 23071148

View details for PubMedCentralID PMC3471227
Native American skin offerings mistaken for acne scars in a college undergraduate. Archives of dermatology Truong, A., Wong, J. W., Chang, A. L. 2012; 148 (10): 1214-1215
View details for DOI 10.1001/archdermatol.2012.592

View details for PubMedID 23069975
EXPANDED ACCESS STUDY OF ADVANCED BCC PATIENTS TREATED WITH THE HEDGEHOG-PATHWAY INHIBITOR VISMODEGIB 37th Congress of the European-Society-for-Medical-Oncology (ESMO) Weiss, G. J., Oro, A., Chang, A. L., Solomon, J. A., Lorusso, P. M., Hamid, O., Chen, D. M., McKenna, E., Feng, S., Hainsworth, J. D. OXFORD UNIV PRESS. 2012: 362?362
View details for Web of Science ID 000309409002049
Translocation Affecting Sonic Hedgehog Genes in Basal-Cell Carcinoma NEW ENGLAND JOURNAL OF MEDICINE Gomez-Ospina, N., Chang, A. L., Qu, K., Oro, A. E. 2012; 366 (23): 2233-2234
View details for Web of Science ID 000304863400029

View details for PubMedID 22670922

View details for PubMedCentralID PMC3839666
Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma NEW ENGLAND JOURNAL OF MEDICINE Sekulic, A., Migden, M. R., Oro, A. E., Dirix, L., Lewis, K. D., Hainsworth, J. D., Solomon, J. A., Yoo, S., Arron, S. T., Friedlander, P. A., Marmur, E., Rudin, C. M., Chang, A. L., Low, J. A., Mackey, H. M., Yauch, R. L., Graham, R. A., Reddy, J. C., Hauschild, A. 2012; 366 (23): 2171-2179
Abstract

Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma.In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma.In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P=0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted.Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.).

View details for Web of Science ID 000304863400006

View details for PubMedID 22670903

View details for PubMedCentralID PMC5278761
Identification of genes promoting exceptional skin youthfulness 75th Annual Meeting of the Society-for-Investigative-Dermatology Chang, A. S., Atzmon, G., Bergman, A., Chang, H. Y., Barzilai, N. NATURE PUBLISHING GROUP. 2012: S65?S65
View details for Web of Science ID 000302866900385
Hedghog pathway inhibitor Vismodegib (GDC-0449) in metastatic basal cell carcinoma Lim, S. W., Chang, A. S., Kelly, J. W. WILEY-BLACKWELL. 2012: 43?44
View details for Web of Science ID 000304248600121
SMO inhibitor effectiveness in a patient with a SHH locus translocation causing holoprosencephaly and basal cell carcinomas Gomez-Ospina, N., Bangs, C. D., Qu, K., Chang, A. L., Oro, A. E. NATURE PUBLISHING GROUP. 2012: S28
View details for Web of Science ID 000302866900168
Efficacy and safety of vismodegib in advanced basal cell carcinoma Chang, A., Sekulic, A., Migden, M. R., Hauschild, A., Lewis, K., Hainsworth, J. D., Yoo, S., Dirix, L., Hou, J., Mackey, H., Oro, A. E. NATURE PUBLISHING GROUP. 2012: S93
View details for Web of Science ID 000302866900549
Rejuvenation of gene expression patterns in aged human skin with broadband light treatment Chang, A. S., Bitter, P., Qu, K., Chang, H. Y. NATURE PUBLISHING GROUP. 2012: S65
View details for Web of Science ID 000302866900383
Dramatically improved overall survival and predictors of disease in 17 metastatic basal cell carcinoma patients 75th Annual Meeting of the Society-for-Investigative-Dermatology Danial, C., Lingala, B., Oro, A. E., Chang, A. S. NATURE PUBLISHING GROUP. 2012: S39?S39
View details for Web of Science ID 000302866900228
Transcriptional profiling to identify genes controlling human skin aging 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) Chang, A. L., Kern, D., Knaggs, H., Gierman, H., Kim, S. MOSBY-ELSEVIER. 2012: AB32?AB32
View details for Web of Science ID 000302319800128
An Exploratory Study to Determine the Association Between Assessed Facial Skin Aging and Plasma Isoprostane Levels in Middle-Aged Japanese Women DERMATOLOGIC SURGERY Chang, A. L., Lingala, B., Chang, T. C., Kern, D. G., Wood, S. M., Toyoda, H., Knaggs, H. E. 2012; 38 (3): 462-470
Abstract

One of the central mechanisms of aging is hypothesized to be oxidative stress. Quantification of oxidative stress in human organ systems has been difficult. One of the best methods is using plasma isoprostane levels, which have been shown to reflect oxidative stress in multiple nondermatologic organ systems.To determine whether severity of aging of human skin is associated with plasma isoprostane levels, specifically prostaglandin F2a (PGF2a) and 8-iso-PGF2a while controlling for covariates such as body mass index, ultraviolet light exposure, diet, medication, supplement use, and stress levels.Facial skin aging assessments performed by four blinded dermatologists were correlated with plasma isoprostane levels in 46 healthy, nonsmoking Japanese women aged 45 to 60.Individuals whose assessed skin age exceeded chronological age had mean plasma isoprostane levels of PGF2a and 8-iso-PGF2a that were higher than those whose skin age was assessed to be less than chronological age (p�=�.001 and .001, respectively). These results remained statistically significant when adjusted for confounding variables (8-iso-PGF2a, p�=�.02; PGF2a, p�=�.03).Plasma isoprostanes as markers of accelerated aging of the skin merit further study.

View details for DOI 10.1111/j.1524-4725.2011.02235.x

View details for Web of Science ID 000300979600017

View details for PubMedID 22141590
A Randomized, Double-Blind, Placebo-Controlled, Pilot Study to Assess the Efficacy and Safety of Clindamycin 1.2% and Tretinoin 0.025% Combination Gel for the Treatment of Acne Rosacea Over 12 Weeks JOURNAL OF DRUGS IN DERMATOLOGY Chang, A. L., Alora-Palli, M., Lima, X. T., Chang, T. C., Cheng, C., Chung, C. M., Amir, O., Kimball, A. B. 2012; 11 (3): 333-339
Abstract

Papulopustular acne rosacea is a chronic inflammatory condition which can be difficult to treat. Many patients are unwilling to use systemic medications, and single topical agents alone may not address all the symptoms of rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025% gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne vulgaris and rosacea shares many similar clinical and histologic features.To assess the preliminary efficacy and safety of a combination gel consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular rosacea after 12 weeks of usage.Randomized, double-blind, placebo controlled two site study of 79 participants with moderate to severe papulopustular acne rosacea using both physician and subjects' validated assessment tools. Primary endpoint consisted of statistically significant reduction in absolute papule or pustule count after 12 weeks of usage.There was no significant difference in papule/pustule count between placebo and treated groups after 12 weeks (P=0.10). However, there was nearly significant improvement in physicians' assessments of the telangiectasia component of rosacea (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus placebo group after 12 weeks. The only significant adverse event different was facial scaling, which was significantly increased in treated group (P=0.01), but this did not result in discontinuation of study drug.A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the telangiectatic component of rosacea and appears to better treat the erythemotelangiectatic subtype of rosacea rather than papulopustular subtype. Our preliminary study suggests that future studies with much larger sample size might confirm our findings.

View details for Web of Science ID 000301315500006

View details for PubMedID 22395584
Differential effects of dietary supplements on metabolomic profile of smokers versus non-smokers Genome Medicine Spitale RC, Cheng MY, Chun KA, Gorell ES, Munoz CA, Kern DG, Wood SM, Knaggs HE, Wulff J, Beebe KD, Chang AS 2012; 4 (2)
Native American Skin Offerings Mistaken for Acne Scars in a College Undergraduate Archives of Dermatology Wong J, Truong AK, Chang AS 2012; 148 (10)
A Little Known But Life Threatening Association of Bullous Pemphigoid and Acquired Hemophilia: Case Report and Review of the Literature Journal of Clinical and Experimental Dermatology Research dx.doi.org/10.4172/2155-9554.S6-003 Nguyen C, Gordon J, Chang AS 2012
Stratification of highest risk patients with chronic skin ulcers in a Stanford retrospective cohort includes diabetes, need for systemic antibiotics and albumin levels Ulcers Amir O, Liu A, Chang AS 2012; ID7678561
A randomized double-blind, placebo-controlled pilot study to assess the efficacy and safety of clindamycin 1.2% and tretinoin 0.025% combination gel for the treatment of acne rosacea over 12 weeks Journal of Drugs in Dermatology Chang, A., Alora-Palli M, Lima XT, Chang TC, Cheng C, Chung CM, Amir O, Kimball AB 2012; 11 (3): 160-66
More Than Just A Coincidence: Herpes Zoster and Acne Rosacea Appearing Together as Wolf?s Isotopic Response in an Asian Female International Journal of Case Reports and Images Fijalkowski N, W. K. 2012; Feb
Initial assessment of tumor regrowth after vismodegib in advanced basal cell carcinoma patients Archives of Dermatology Chang AS, Oro AE 2012; Aug 20 (epub)
A phase I study of IPI-926, a novel hedgehog pathway inhibitor, in patients (pts) with advanced or metastatic solid tumors. Rudin, C. M., Jimeno, A., Miller, W. H., Eigl, B. J., Gettinger, S. N., Chang, A. S., Faia, K., Sweeney, J., Loewen, G., Ross, R. W., Weiss, G. J. AMER SOC CLINICAL ONCOLOGY. 2011
View details for DOI 10.1200/jco.2011.29.15_suppl.3014

View details for Web of Science ID 000208880301443
Not so positive: Optimism and public self-consciousness were not associated with the placebo response in a rosacea trial. 71st Annual Meeting of the Society-for-Investigative-Dermatology Kardos, M., Kim, G., Chang, A. S., Kimball, A. B. NATURE PUBLISHING GROUP. 2011: S37?S37
View details for Web of Science ID 000289035600222
Association of skin aging severity with blood isoprostane levels in healthy middle-aged Japanese women 71st Annual Meeting of the Society-for-Investigative-Dermatology Chang, T. C., Lingala, B., Kern, D. G., Wood, S. M., Toyoda, H., Knaggs, H., Chang, A. S. NATURE PUBLISHING GROUP. 2011: S85?S85
View details for Web of Science ID 000289035600508
Facial skin aging and association with blood markers of oxidative stress Chang, A., Morre, D., Kern, D., Morre, D., Wood, S. M. MOSBY-ELSEVIER. 2011: AB21
View details for Web of Science ID 000286780500082
Getting the word out: A fast intervention to educate nonmedical skin care professionals at salons and spas in southern California about tanning bed usage and skin cancer 69th Annual Meeting of the American-Academy-of-Dermatology Ng, A., Chang, A. L., Peng, D. MOSBY-ELSEVIER. 2011: AB78?AB78
View details for Web of Science ID 000286780500307
Association of facial skin aging and vitamin D levels in healthy middle-aged white women Chang, A., Tang, J., Amir, O., Fu, T. MOSBY-ELSEVIER. 2011: AB2
View details for Web of Science ID 000286780500007
A case of Cinderella: erythema dyschromia perstans (ashy dermatosis or dermatosis cinecienta) SkinMed: Dermatology for the Clinician Munoz CA, Chang AS 2011; 9 (1): 63-4
Association of facial skin aging and vitamin D levels in middle-aged white women CANCER CAUSES & CONTROL Chang, A. L., Fu, T., Amir, O., Tang, J. Y. 2010; 21 (12): 2315-2316
Abstract

To investigate the relationship between UV-induced skin photodamage and 25(OH) vitamin D levels, we performed a cross-sectional study in 45 female subjects aged >40. Menopausal status, smoking status, skin cancer history, oral supplement use, and season of blood draw were recorded and serum 25(OH)D measured. A single-blinded, dermatologist evaluated standardized digital facial images for overall photodamage, erythema/telangiectasias, hyperpigmentation, number of lentigines, and wrinkling. Adjusting for age and season of blood collection, women with lower photodamage scores were associated with a 5-fold increased odds of being vitamin D insufficient (OR 5.0, 95% CI: 1.1, 23). Low scores for specific photodamage parameters including erythema/telangiectasias, hyperpigmentation, and wrinkling were also significantly associated with vitamin D insufficiency. Our results suggest an association between skin aging and 25(OH)D levels.

View details for DOI 10.1007/s10552-010-9646-y

View details for Web of Science ID 000288609600041

View details for PubMedID 20882333

View details for PubMedCentralID PMC3042365
A PHASE 1 STUDY OF IPI-926, AN INHIBITOR OF THE HEDGEHOG PATHWAY, IN PATIENTS (PTS) WITH ADVANCED OR METASTATIC SOLID TUMORS Rudin, C. M., Weiss, G. J., Chang, A., Gettinger, S., Miller, W. H., Eigl, B., Savage, A., Loewen, G., Ross, R. W., Jimeno, A. OXFORD UNIV PRESS. 2010: 164
View details for Web of Science ID 000283115900514
Initial Clinical Experience Using a Novel Ultraportable Negative Pressure Wound Therapy Device WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE Fong, K. D., Hu, D., Eichstadt, S. L., Gorell, E., Munoz, C. A., Lorenz, H. P., Chang, A. L. 2010; 22 (9): 230-236
Abstract

??? Background. Traditional negative pressure wound therapy (NPWT) devices, such as the electrically powered V.A.C.� Therapy System (KCI, San Antonio, TX), are important tools in the treatment of both acute and chronic wounds. The following describes the first clinical experience using a novel, non-electrically powered, ultraportable NPWT device called the Smart Negative Pressure (SNaP?) Wound Care System (Spiracur, Sunnyvale, CA).Twelve consecutive adult subjects with chronic wounds ranging from neuropathic wounds to venous stasis ulcers were treated with the SNaP System at an academic outpatient dermatology clinic. Subjects were followed biweekly for complications and wound healing progression over a 4-week period.Of the 12 subjects treated, 5 achieved complete wound healing within 4 weeks. All subjects demonstrated healing after treatment with the SNaP System, and statistically significant healing was reached at 4 weeks (P < 0.01) for patients who were able to complete the treatment protocol. Use of the SNaP System promoted cleaner wound beds with robust granulation tissue formation. There were no serious adverse events directly related to the device. The most common complaint was mild or moderate wound pain in 3 of 12 subjects.These findings support the safety and potential clinical utility of a new ultraportable NPWT device for the treatment of chronic wounds. ? ??.

View details for Web of Science ID 000285531700007
A single-blind pilot study of oral antioxidant supplementation on skin aging parameters and age associated blood metabolites in female smokers 68th Annual Meeting of the American-Academy-of-Dermatology Chang, A. L., Munoz, C., Kern, D., Gorell, E., Wood, S. MOSBY-ELSEVIER. 2010: AB19?AB19
View details for Web of Science ID 000275880700070
??????Initial clinical experience using a novel ultraportable negative pressure wound therapy device. Wounds : a compendium of clinical research and practice Fong, K. D., Hu, D., Eichstadt, S. L., Gorell, E., Munoz, C. A., Lorenz, H. P., Chang, A. L. 2010; 22 (9): 230?36
Abstract

??? Background. Traditional negative pressure wound therapy (NPWT) devices, such as the electrically powered V.A.C.� Therapy System (KCI, San Antonio, TX), are important tools in the treatment of both acute and chronic wounds. The following describes the first clinical experience using a novel, non-electrically powered, ultraportable NPWT device called the Smart Negative Pressure (SNaP?) Wound Care System (Spiracur, Sunnyvale, CA).Twelve consecutive adult subjects with chronic wounds ranging from neuropathic wounds to venous stasis ulcers were treated with the SNaP System at an academic outpatient dermatology clinic. Subjects were followed biweekly for complications and wound healing progression over a 4-week period.Of the 12 subjects treated, 5 achieved complete wound healing within 4 weeks. All subjects demonstrated healing after treatment with the SNaP System, and statistically significant healing was reached at 4 weeks (P < 0.01) for patients who were able to complete the treatment protocol. Use of the SNaP System promoted cleaner wound beds with robust granulation tissue formation. There were no serious adverse events directly related to the device. The most common complaint was mild or moderate wound pain in 3 of 12 subjects.These findings support the safety and potential clinical utility of a new ultraportable NPWT device for the treatment of chronic wounds. ? ??.

View details for PubMedID 25901554
A Two-Year, Double-Blind, Randomized Placebo-Controlled Trial of Oral Green Tea Polyphenols on the Long-Term Clinical and Histologic Appearance of Photoaging Skin DERMATOLOGIC SURGERY Janjua, R., Munoz, C., Gorell, E., Rehmus, W., Egbert, B., Kern, D., Chang, A. L. 2009; 35 (7): 1057-1065
Abstract

Green tea polyphenols (GTPs) have significant antioxidant and antiinflammatory activities, and prior short-term studies suggest that these compounds may improve photoaging skin.To evaluate the long-term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin.Double-blind, placebo-controlled trial of 56 women aged 25 to 75 randomized to 250 mg GTPs or placebo twice daily for 2 years. A blinded dermatologist scored the appearance of photodamaged facial skin at 0, 6, 12, and 24 months. A blinded dermatopathologist scored the histologic characteristics of sun-exposed arm skin at 0 and 24 months.Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months (p=.02) and significant improvement in erythema and telangiectasias at 12 months (p=.02). The placebo group did not have significant improvements in these parameters at 6 months or 12 months. There were no statistically significant differences in other photoaging parameters at 6, 12, or 24 months in the GTP or placebo groups. Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months.Long-term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use.

View details for DOI 10.1111/j.1524-4725.2009.01183.x

View details for Web of Science ID 000267658700006

View details for PubMedID 19469799
Preventing Diabetic Skin Ulcers in Latinos-No Small Feat: Development of a Spanish and English Survey for Fast Assessment of Lower Extremity Skin Care Practices ARCHIVES OF DERMATOLOGY Munoz, C., Chang, A. S. 2009; 145 (4): 486?88
View details for Web of Science ID 000265411100021

View details for PubMedID 19380678
A 2-year, double-blind, randomized, placebo-controlled trial of oral green tea polyphenols on the long-term clinical and histologic appearance of photoaging skin Chang, A., Egbert, B., Munoz, C., Janjua, R., Rehmus, W. MOSBY-ELSEVIER. 2009: AB29
View details for Web of Science ID 000263934100115
Oral contraceptives for acne and sexual practices JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Abuabara, K., Chang, A. S. 2009; 60 (3): 515?16
View details for DOI 10.1016/j.jaad.2008.09.042

View details for Web of Science ID 000263934000025

View details for PubMedID 19231651
Preventing diabetic skin ulcers in Latinos-- no small feat: development of a Spanish and English survey for fast assessment of lower extremity skin care practices Archives of Dermatology Munoz, C., Chang, AS 2009; 145 (4): 486-488
Oral contraceptives for acne and sexual practices Journal of the American Academy of Dermatology Abuabara K, Chang AL 2009; 60 (3): 515-6
Adoption of Western Culture By Californian Asian Americans: Attitudes and Practices Promoting Sun Exposure Archives of Dermatology Gorell ES, Lee C, Munoz CA, Chang AS 2009; 145 (5): 552-555
Alefacept for erosive lichen planus: A case series JOURNAL OF DRUGS IN DERMATOLOGY Chang, A. L., Badger, J., Rehmus, W., Kimball, A. B. 2008; 7 (4): 379-383
Abstract

Erosive mucosal lichen planus is thought to be an autoimmune disease mediated by increased T-cell activation and proliferation. Alefacept is a biologic agent that selectively targets memory T cells.To evaluate the preliminary efficacy and safety of alefacept in the treatment of moderate to severe mucosal LP.Seven subjects were randomly selected to receive either alefacept 15 mg or placebo every week for 12 weeks. Endpoints of the case series were the Physician Global Assessment (PGA) of disease severity, mucosal pain (MP) severity, and itch severity (IS). Both subjects and investigators were blinded.Two of the subjects receiving alefacept achieved significant improvement during the study. There were no serious adverse events during the course of the study period.In this small case series, alefacept may have conferred a modest therapeutic response in erosive lichen planus (LP). Larger multicenter prospective studies will be needed to determine whether alefacept can improve erosive LP in a statistically significant way.

View details for Web of Science ID 000255376000010

View details for PubMedID 18459520
Factors affecting sun protection and skin cancer prevention knowledge, attitudes and practices in Asian-Americans living in Northern California International Investigative Dermatology Meeting Chang, A. S., Gorell, E. S., Lee, C., Munoz, C. A. NATURE PUBLISHING GROUP. 2008: S84?S84
View details for Web of Science ID 000254353800498
A case of argyria after colloidal silver ingestion JOURNAL OF CUTANEOUS PATHOLOGY Chang, A. L., Khosravi, V., Egbert, B. 2006; 33 (12): 809-811
Abstract

Argyria is often considered an entity of the past, one which has largely disappeared with the cessation of silver usage in oral medications. However, with the practice of colloidal silver ingestion in current "alternative health" treatments, argyria should be considered in the differential diagnosis of blue-gray hyperpigmentation.A single case report with clinicopathological correlation.Histological examination of skin biopsy specimen, which showed perieccrine brown-black granules, verified that colloidal silver rather than a prescribed medication was the source of the patient's dyspigmentation.

View details for DOI 10.1111/j.1600-0560.2006.00557.x

View details for Web of Science ID 000242658700007

View details for PubMedID 17177941
Risk factors associated with striae gravidarum 65th Annual Meeting of the Society-for-Investigative-Dermatology Chang, A. L., Agredano, Y. Z., Kimball, A. B. MOSBY-ELSEVIER. 2004: 881?85
Abstract

Striae gravidarum (SG) is a poorly characterized but common disfiguring condition of pregnancy.To better characterize the epidemiological factors associated with SG.An anonymous survey administered at Stanford Ambulatory Clinics sampled 161 women who had given birth.Forty-eight-point-three percent of women with SG (43/89) versus 19.4% without SG (14/72) reported mothers with SG (odds ratio = 7.0, 95% confidence interval [CI] 2.7, 18.6). Forty-seven percent of women with SG (42/89 women) versus 18.1% without SG (13/72) reported additional relatives with SG (odds ratio = 7.2, 95% CI 2.9, 18.2). Eighty-one percent of women with SG (68/84) versus 30.5% without SG (18/59) reported a history of breast or thigh striae (odds ratio = 8.6, 95% CI 3.8, 19.9). Forty-seven percent of women with SG versus 17% without SG were non-white (odds ratio = 4.2, 95% CI 1.9, 9.6).This study suggests that a history of breast or thigh striae, family history, and race is significantly predictive of SG development.

View details for DOI 10.1016/j.jaad.2004.05.030

View details for Web of Science ID 000225745300002

View details for PubMedID 15583577
Risk factors associated with striae gravidarum 65th Annual Meeting of the Society-for-Investigative-Dermatology Chang, A. S., Agredano, Y. Z., Kimball, A. B. NATURE PUBLISHING GROUP. 2004: A60?A60
View details for Web of Science ID 000220660500410
Salpingectomy or proximal tubal occlusion of unilateral hydrosalpinx increases the potential for spontaneous pregnancy. Human Reprod Sagoskin AW, Lessey BA, Mottla GL, Richter KS, Chetkowski RJ, Chang AS, Levy MJ, Stillman RJ. 2003; 18 (12): 2634-7
Obstetric attending physician characteristics and their impact on vacuum and forceps delivery rates: University of California at San Francisco experience from 1977 to 1999. Am J Obstet Gynecol Chang AL, Noah MS, Laros RK 2002; 186 (6): 1299-303
Talin and vinculin play distinct roles in filopodial motility in the neuronal growth cone J Cell Biol. Sydor AM, Su AL, Wang FS, Xu A, Jay DG 1996; 134 (5): 1197-207
Chromophore-assisted laser inactivation of patched protein switches cell fate in the larval visual system of Drosophila. Proc Natl Acad Sci U S A 1996; 91 (7): 2664-8

Anne Lynn S. Chang, MD

Professor of Dermatology at the Stanford University Medical Center

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