Anne Lynn S. Chang, MD

All Publications

• A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of Groups 1, 2, and 3, and primary analysis of fixed-dose treatment Group 6. Journal of the American Academy of Dermatology Hughes, B. G., Guminski, A., Bowyer, S., Migden, M. R., Schmults, C. D., Khushalani, N. I., Chang, A. L., Grob, J. J., Lewis, K. D., Ansstas, G., Day, F., Ladwa, R., Stein, B. N., Muñoz Couselo, E., Meier, F., Hauschild, A., Schadendorf, D., Basset-Seguin, N., Modi, B., Dalac-Rat, S., Dunn, L. A., Flatz, L., Mortier, L., Guégan, S., Heinzerling, L. M., Mehnert, J. M., Trabelsi, S., Soria-Rivas, A., Stratigos, A. J., Ulrich, C., Wong, D. J., Beylot-Barry, M., Bossi, P., Bugés Sánchez, C., Chandra, S., Robert, C., Russell, J. S., Silk, A. W., Booth, J., Yoo, S. Y., Seebach, F., Lowy, I., Fury, M. G., Rischin, D. 2024

  Abstract

  In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC).To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (Groups 1 and 2), fixed-dose cemiplimab in mCSCC (Group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (Group 6).Patients received cemiplimab (3 mg/kg intravenously [IV] every 2 weeks [Groups 1 and 2]) or cemiplimab (350 mg IV [Groups 3 and 6]) every 3 weeks. The primary endpoint was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments.At 42.5 months, ORR for Groups 1-3 (n=193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for Group 6 (n=165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were Groups 1-3: 31.1% and Group 6: 34.5%.Non-randomized study, non-survival primary endpoint.EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.

  View details for DOI 10.1016/j.jaad.2024.06.108

  View details for PubMedID 39245360

• Novel Strategy for Strengthening Dermatoporotic Skin by Managing Cellular Senescence. Journal of drugs in dermatology : JDD Widgerow, A. D., Ziegler, M., Garruto, J. A., Ionescu, L., Shafiq, F., Meckfessel, M., Lain, E. T., Ablon, G., Harper, J., Chang, A. L., Howard-Verovic, C. 2024; 23 (9): 748-756

  Abstract

  Dermatoporosis (DP) is a condition associated with thinning skin layers and resultant fragility. Much of the thinning is related to fibroblast dysfunction, production of destructive inflammatory cytokines, breakdown of the extracellular matrix (ECM), and weakening of the dermo-epidermal junction. A major contributor to this change in the ECM milieu, previously under-considered, is cellular senescence, particularly involving the papillary dermal fibroblasts.A series of experiments were undertaken to explore the impact of a combination of known actives on senescent cell status. Human keratinocytes and fibroblasts were cultured, and cytotoxicity tests were performed to determine the ideal concentration to avoid cell toxicity. Microdoses of Centella asiatica (0.005%) and mandelic acid (0.05%) were found to be ideal in avoiding any cytotoxicity. However, the challenge was then to assess the efficacy of these actives in this microdosed form. After exposing the cells to the compounds, RNA was isolated and sequenced. Moreover, a well-described ex vivo model using photodamaged skin was subjected to immunofluorescence to identify senescent cells (via p16INK4a), particularly in the papillary dermis, using the microdose formulation compared to untreated skin. In addition, JAG/NOTCH expression in the epidermal basal cells was evaluated to further understand the cellular senescence signaling mechanism.Microdosing these two well-known agents had surprisingly significant synergistic effects in vitro, decreasing senescence-associated secretory phenotype (SASP) cytokines and the associated inflammation involved in the process. The ex vivo model revealed a significant (P<0.05) decrease in senescent cells in the papillary dermis and a significant increase (P<0.001) of JAG/NOTCH expression in the basal cells of the epidermis.Using microdoses of two known agents, a novel approach produced an unexpected effect of reversal of dermal senescent cells and promoting an anti-inflammatory milieu. A gene expression analysis of the individual and combined actives validated these observations, followed by full formulation testing in an ex vivo model. The approach of limiting cellular senescence in dermal fibroblasts for managing DP is novel and provides an exciting new direction to address dermatoporosis. Clinical studies will follow. J Drugs Dermatol. 2024;23(9):748-756. doi:10.36849/JDD.8388.

  View details for DOI 10.36849/JDD.8388

  View details for PubMedID 39231083

• Therapeutic strategies focusing on immune dysregulation and neuroinflammation in rosacea. Frontiers in immunology Tu, K. Y., Jung, C. J., Shih, Y. H., Chang, A. L. 2024; 15: 1403798

  Abstract

  Rosacea is a complex inflammatory condition characterized by papulopustular lesions and erythema on the central face for which there is no cure. The development of rosacea is influenced by both external triggers and genetics, but the common pathophysiology is overactivation of the immune system. Here, we review the current data on proinflammatory cytokines and dysregulation of the neurovascular system as targetable components of rosacea. Amelioration of cutaneous and gastrointestinal dysbiosis and other external factors impacts the immune state and has been observed to improve rosacea. While multiple treatments exist, many patients do not achieve their goals for rosacea control and highlights an unmet need for dermatologic care. Current interventions encompass topical/oral drugs, light devices, and avoidance of triggers management. Additional understanding of the underlying pathogenesis may help us develop novel targeted therapeutic strategies to improve rosacea.

  View details for DOI 10.3389/fimmu.2024.1403798

  View details for PubMedID 39136023

  View details for PubMedCentralID PMC11317294

• Health-related quality of life in patients with metastatic basal cell carcinoma treated with cemiplimab: Analysis of a phase 2 trial. Cancer medicine Peris, K., Inocencio, T. J., Stratigos, A. J., Lewis, K. D., Eroglu, Z., Chang, A. L., Ivanescu, C., Sekulic, A., Fury, M. G., Chen, C. I., Quek, R. G. 2024; 13 (14): e7360

  Abstract

  A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health-related quality of life (QoL) for this patient population is reported.Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales.Patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales.The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.

  View details for DOI 10.1002/cam4.7360

  View details for PubMedID 39031963

  View details for PubMedCentralID PMC11259569

• Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach. The American Journal of dermatopathology Chang, A. L., Brown, R., Li, S., Betancourt, N., Teng, J. 2024

  Abstract

  Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.

  View details for DOI 10.1097/DAD.0000000000002718

  View details for PubMedID 38648034

• Resolution of metastatic neck nodes associated with a periauricular cutaneous squamous cell carcinoma after intranodal injection of talimogene laherparepvec. JAAD case reports Che, Y., Chong, C., Limova, M., Morris, L., Reddy, S. A., Chang, A. L. 2024; 46: 92-94

  View details for DOI 10.1016/j.jdcr.2024.02.008

  View details for PubMedID 38577494

  View details for PubMedCentralID PMC10992271

• Shared decision-making for older adult dermatology patients (cover article) The Dermatologist Manjunath, J., Zhong, X., Onyeka, S., Chang, A. S., Butler, D. 2024; 32 (5): 33-35
• Headache and Dermatologic Conditions Comorbid Conditions in the Treatment of Headache edited by Moskatel, L. S., Cowan, R. P. Routledge Taylor & Francis Group. 2024; 1
• LGBTQ+ inclusive language in patient-reported outcome measures for acne vulgaris: a qualitative study JAMA Dermatology Sia, T., Abou-Taleb, F., Yeung, H., Chang, A. S. 2024; Accepted
• Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors. Annals of oncology : official journal of the European Society for Medical Oncology Lewis, K. D., Peris, K., Sekulic, A., Stratigos, A. J., Dunn, L., Eroglu, Z., Chang, A. L., Migden, M. R., Yoo, S. Y., Mohan, K., Coates, E., Okoye, E., Bowler, T., Baurain, J. F., Bechter, O., Hauschild, A., Butler, M. O., Hernandez-Aya, L., Licitra, L., Neves, R. I., Ruiz, E. S., Seebach, F., Lowy, I., Goncalves, P., Fury, M. G. 2023

  Abstract

  Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks binding of programmed cell death-1 (PD-1) to its ligands, PD-L1 and PD-L2. Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitors (HHIs) (NCT03132636).In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints included ORR per investigator assessment (INV), progression-free survival (PFS), overall survival (OS), complete response (CR) rate, safety and tolerability.Fifty-four patients were enrolled (70% male, median age 64 years [interquartile range (IQR) 57.0-73.0]). Median duration of follow-up was 8 months (IQR 4-21). ORR per ICR was 22% (95% confidence interval [CI] 12-36), with two CRs and 10 partial responses. Among responders, median time to response per ICR was 3 months (IQR 2-7). Estimated median DOR per ICR was not reached (95% CI 10 months-not evaluable [NE]). Disease control rate was 63% (95% CI 49-76) per ICR and 70% (95% CI 56-82) per INV. Median PFS per ICR was 10 months (95% CI 4-16); median OS was 50 months (95% CI 28-NE). The most common treatment-emergent adverse events were fatigue (23 [43%]) and diarrhoea (20 [37%]). There were no treatment-related deaths.Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

  View details for DOI 10.1016/j.annonc.2023.10.123

  View details for PubMedID 38072158

• Phase 2 open-label, multicenter, single-arm study of cemiplimab in patients with locally advanced basal cell carcinoma after hedgehog inhibitor therapy: Extended follow-up. Journal of the American Academy of Dermatology Stratigos, A. J., Sekulic, A., Peris, K., Bechter, O., Prey, S., Lewis, K. D., Basset-Seguin, N., Chang, A. L., Dalle, S., Fernandez Orland, A., Licitra, L., Robert, C., Ulrich, C., Hauschild, A., Migden, M. R., Dummer, R., Yoo, S. Y., Okoye, E., Bassukas, I., Loquai, C., De Giorgi, V., Eroglu, Z., Gutzmer, R., Ulrich, J., Puig, S., Inocencio, T. J., Chen, C. I., LaFontaine, P. R., Seebach, F., Lowy, I., Fury, M. G. 2023

  View details for DOI 10.1016/j.jaad.2023.08.111

  View details for PubMedID 37839734

• An exploratory, comparative case series of calcitonin gene-related peptide monoclonal antibodies in migraine patients with rosacea. The British journal of dermatology Sia, T., Webb, T., Li, S., Moskatel, L. S., Chang, A. L. 2023

  View details for DOI 10.1093/bjd/ljad277

  View details for PubMedID 37596936

• Advances in cutaneous squamous cell carcinoma. Nature reviews. Cancer Winge, M. C., Kellman, L. N., Guo, K., Tang, J. Y., Swetter, S. M., Aasi, S. Z., Sarin, K. Y., Chang, A. L., Khavari, P. A. 2023

  Abstract

  Human malignancies arise predominantly in tissues of epithelial origin, where the stepwise transformation from healthy epithelium to premalignant dysplasia to invasive neoplasia involves sequential dysregulation of biological networks that govern essential functions of epithelial homeostasis. Cutaneous squamous cell carcinoma (cSCC) is a prototype epithelial malignancy, often with a high tumour mutational burden. A plethora of risk genes, dominated by UV-induced sun damage, drive disease progression in conjunction with stromal interactions and local immunomodulation, enabling continuous tumour growth. Recent studies have identified subpopulations of SCC cells that specifically interact with the tumour microenvironment. These advances, along with increased knowledge of the impact of germline genetics and somatic mutations on cSCC development, have led to a greater appreciation of the complexity of skin cancer pathogenesis and have enabled progress in neoadjuvant immunotherapy, which has improved pathological complete response rates. Although measures for the prevention and therapeutic management of cSCC are associated with clinical benefit, the prognosis remains poor for advanced disease. Elucidating how the genetic mechanisms that drive cSCC interact with the tumour microenvironment is a current focus in efforts to understand, prevent and treat cSCC.

  View details for DOI 10.1038/s41568-023-00583-5

  View details for PubMedID 37286893

  View details for PubMedCentralID 4833641

• Immunotherapy for keratinocyte cancers. Part II: Identification and management of cutaneous side effects of immunotherapy treatments. Journal of the American Academy of Dermatology Chang, A. L., Zaba, L., Kwong, B. Y. 2023; 88 (6): 1243-1255

  Abstract

  Keratinocytic cancers (KCs), specifically cutaneous squamous cell and basal cell carcinomas, can respond to topical, intralesional, or systemic immunotherapies, but cutaneous adverse events (CAEs) may occur. Understanding these risks, early recognition of these CAEs, and effective treatment may enable patients to continue their anticancer immunotherapies without dose impact. Immune checkpoint inhibitor-related CAEs after KCs can have multiple clinical presentations, with specific observed types including psoriasis and bullous pemphigoid. Cutaneous toxicities can require biopsies to confirm the diagnosis, especially in patients who are not responsive to topical or oral steroids, since the selection of biologic drugs depends on accurate diagnosis. Different types of CAEs from immune checkpoint inhibitors have been associated with different oncologic outcomes in various primary cancer types, and this remains to be determined for KC patients. CAE characterization and management after immune checkpoint inhibitors in KC patients is a rapidly growing field that needs specific and prospective studies.

  View details for DOI 10.1016/j.jaad.2022.07.062

  View details for PubMedID 37268391

• Use of calcitonin gene-related peptide monoclonal antibodies in patients with rosacea: An exploratory, comparative case series Sia, T., Webb, T., Li, S., Moskatel, L., Chang, A. L. ELSEVIER SCIENCE INC. 2023: S80

  View details for Web of Science ID 001037960300468

• Immunotherapy for Keratinocyte Cancers. Part 1: Immune-Related Epidemiology, Risk Factors, Pathogenesis, and Immunotherapy Management of Keratinocytic Cancers Journal of the American Academy of Dermatology Neuner, R., Lee, J., Park, C., Rieger, K. E., Colevas, A. D., Chang, A. S. 2023; 88 (6): 1225-1240

  View details for DOI 10.1016/j.jaad.2022.06.1206

• Correlation of Ultraviolet Radiation Levels With the Incidence of Cutaneous Squamous Cell and Merkel Cell Carcinomas in Non-sunbelt Locales in the United States: 2010-2017 Cureus: Journal of Medical Science Vora, P. S., Li, S., Oh, G., Webb, T., Perry, W. M., Park, C., Chang, A. S. 2023; 15 (6): e40099

  View details for DOI 10.7759/cureus.40099

• KEYNOTE-630: Phase 3 study of pembrolizumab as adjuvant treatment in high-risk locally advanced (LA) cutaneous squamous cell carcinoma (cSCC) Lee, J., Dzienis, M., Schmults, C., Schneker, M., Bratland, A., Klochikhin, M., Gifoni, M., Kirtbaya, D., Rivera-Diaz, J., Chipman, M., Geiger, J. L., Chang, A. S., Daniels, G. A., Cohen, E. W., Yao, L., Gumuscu, B., Yuan, J., Guminski, A., Bowers, E. WILEY. 2022: 234-235

  View details for Web of Science ID 000871956500405

• Incorporating the "4Ms" framework to improve outpatient geriatric dermatology care. Journal of the American Geriatrics Society Perry, W. M., Vora, P., Oh, G., Park, C., Chang, A. L. 2022

  View details for DOI 10.1111/jgs.18060

  View details for PubMedID 36205447

• Primary analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors Lewis, K. D., Perris, K., Sekulic, A., Stratigos, A., Duecker, P., Eroglu, Z., Chang, A. S., Migden, M. R., Yoo, S. Y., Mohan, K., Coates, E., Okoye, E., Baurain, J. F., Bechter, O., Hauschild, A., Butler, M. O., Hernandez-Aya, L., Licitra, L., Neves, R. I., Ruiz, E. S., Seebach, F., Lowy, I., Goncalves, P., Fury, M. G. WILEY. 2022: 105-106

  View details for Web of Science ID 000851869200181

• Phase II study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): Final analysis from EMPOWER-CSCC-1 groups 1, 2 and 3 Migden, M. R., Schmults, C., Khushanlani, N., Guminski, A., Chang, A. L., Lewis, K., Ansstas, G., Bowyer, S. E., Hughes, B. M., Schadendorf, D., Modi, B., Dunn, L., Flatz, L., Hauschild, A., Yoo, S., Booth, J., Seebach, F., Lowy, I., Fury, M. G., Rischin, D. ELSEVIER. 2022: S918-S919

  View details for DOI 10.1016/j.annonc.2022.07.940

  View details for Web of Science ID 000866211601085

• Phase 2 study of cemiplimab in patients with locally advanced basal cell carcinoma after hedgehog inhibitor therapy: Long-term follow-up Stratigos, A., Sekulic, A., Perris, K., Bechter, O., Prey, S., Kaatz, M., Lewis, K. D., Basset-Sequin, N., Chang, A. S., Dalle, S., Orland, A., Licitra, L., Robert, C., Ulrich, C., Hauschild, A., Migden, M. R., Dummer, R., Yoo, S. Y., Coates, E., Okoye, E., Bowler, T., Bassukas, I., Loquai, C., De Giorgi, V., Eroglu, Z., Gutzmer, R., Ulrich, J., Puig, S., Seebach, F., Fury, M. G. WILEY. 2022: 38-39

  View details for Web of Science ID 000851869200062

• Partnering with a senior living community to optimize teledermatology via full body skin screening during the COVID-19 pandemic: a pilot program Skin Health and Disease Trinh, P., Yekrang, K., Phung, M., Pugliese, S., Chang, A. S., Bailey, E. E., Ko, J. M., Sarin, K. Y. 2022; 2 (3): e141

  View details for DOI 10.1002/ski2.141

• Recurrent bilateral cutaneous squamous cell carcinoma arising within hypertrophic lichen planus with metastasis while on cemiplimab Leeolou, M. C., Burgren, N. M., Lee, C. S., Momeni, A., Pinto, H., Johannet, P., Liebert, C., Nord, K. M., Chang, A. S. JAAD case reports. 2022 ; Case Report (Volume 29): 55-58
• Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry. PloS one Sekulic, A., Yoo, S., Kudchadkar, R., Guillen, J., Rogers, G., Chang, A. L., Guenthner, S., Raskin, B., Dawson, K., Mun, Y., Chu, L., McKenna, E., Lacouture, M. 1800; 17 (1): e0262151

  Abstract

  BACKGROUND: Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States.METHODS: This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor-naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings.RESULTS: Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment.CONCLUSIONS: This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

  View details for DOI 10.1371/journal.pone.0262151

  View details for PubMedID 35030185

• Phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): follow-up at 43 months 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., Yoo, S., Okoye, E., Lowy, I., Fury, M. G., Migden, M. R. WILEY. 2021: 166

  View details for Web of Science ID 000717281500265

• A 10-year retrospective cohort study of ruxolitinib and association with non-melanoma skin cancer in polycythemia vera and myelofibrosis patients. Journal of the American Academy of Dermatology Lin, J. Q., Li, S. Q., Li, S., Kiamanesh, E. F., Aasi, S. Z., Kwong, B. Y., Chang, A. L. 2021

  Abstract

  BACKGROUND: Clinical trials report occurrence of non-melanoma skin cancers (NMSC) with ruxolitinib in polycythemia (PV) or myelofibrosis (MF) patients, however the level of risk and effect of covariates are not known in the real-world setting.OBJECTIVE: To systematically assess the risk of developing non-melanoma skin cancer (NMSC) after ruxolitinib exposure in PV or MF patients.METHODS: A 10-year retrospective cohort of PV or MF patients at Stanford Medical Center was identified and matched on age, gender, race, Charlson comorbidity index, disease diagnosis, and follow-up time. The main outcome measure was Hazard Ratio (HR) for NMSC (comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) after ruxolitinib exposure, adjusted for covariates.RESULTS: The study cohort consisted of 564 patients (188 exposed to ruxolitinib for at least 4 weeks, 376 unexposed). Ruxolitinib-exposed PV or MF patients had an adjusted NMSC HR of 2.69 (95% Confidence Interval (CI), 1.03-7.02). In particular, ruxolitinib exposure was associated with SCC, HR=3.24 (95% CI, 1.45-7.22), with non-JAK2 mutated patients showing even higher SCC risk, HR=7.40 (2.54-21.63).LIMITATIONS: Retrospective design.CONCLUSIONS AND RELEVANCE: Our real-world results indicate that SCC risk is increased in PV or MF patients taking ruxolitinib and supports consideration of skin cancer monitoring.

  View details for DOI 10.1016/j.jaad.2021.10.004

  View details for PubMedID 34648874

• Health-related Quality of Life (HRQoL) in Patients with advanced cutaneous Squamous Cell Carcinoma (CSCC) treated with Cemiplimab: Post hoc exploratory Analysis of a clinical Phase-2-Study Migden, M. R., 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., Lowy, I., Fury, M. G., Li, S., Chen, C. I. WILEY. 2021: 22

  View details for Web of Science ID 000693238000035

• Antineoplastic therapy after discontinuation of sonidegib 200 mg in patients with advanced basal cell carcinoma: Results from the 42-month, randomized, double-blind BOLT study Gutzmer, R., Guminski, A., Foley, P., Chang, A. S., Lewis, K., Squittieri, N., Loquai, C. MOSBY-ELSEVIER. 2021: AB89

  View details for Web of Science ID 000683887500348

• Primary Analysis of Phase-2-Results for Cemiplimab in Patients (pts) with locally advanced Basal Cell Carcinoma (laBCC) who progress or cannot tolerate Hedgehog Inhibitors (HHI) Stratigos, A. J., Sekulic, A., Peris, K., Bechter, O., Dutriaux, C., Kaatz, M., Lewis, K. D., Basset-Seguin, N., Chang, A. S., Dalle, S., Orland, A., Licitra, L., Robert, C., Ulrich, C., Hauschild, A., Migden, M. R., Dummer, R., Li, S., Bowler, T., Fury, M. G. WILEY. 2021: 41-42

  View details for Web of Science ID 000693238000074

• Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. Journal for immunotherapy of cancer Rischin, D., Khushalani, N. I., Schmults, C. D., Guminski, A., Chang, A. L., Lewis, K. D., Lim, A. M., Hernandez-Aya, L., Hughes, B. G., Schadendorf, D., Hauschild, A., Thai, A. A., Stankevich, E., Booth, J., Yoo, S., Li, S., Chen, Z., Okoye, E., Chen, C., Mastey, V., Sasane, M., Lowy, I., Fury, M. G., Migden, M. R. 2021; 9 (8)

  Abstract

  BACKGROUND: To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL).METHODS: Patients received cemiplimab 3mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks).RESULTS: Median duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001).CONCLUSIONS: This is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.

  View details for DOI 10.1136/jitc-2021-002757

  View details for PubMedID 34413166

• Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. The Lancet. Oncology Stratigos, A. J., Sekulic, A., Peris, K., Bechter, O., Prey, S., Kaatz, M., Lewis, K. D., Basset-Seguin, N., Chang, A. L., Dalle, S., Orland, A. F., Licitra, L., Robert, C., Ulrich, C., Hauschild, A., Migden, M. R., Dummer, R., Li, S., Yoo, S., Mohan, K., Coates, E., Jankovic, V., Fiaschi, N., Okoye, E., Bassukas, I. D., Loquai, C., De Giorgi, V., Eroglu, Z., Gutzmer, R., Ulrich, J., Puig, S., Seebach, F., Thurston, G., Weinreich, D. M., Yancopoulos, G. D., Lowy, I., Bowler, T., Fury, M. G. 2021

  Abstract

  BACKGROUND: Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy.METHODS: We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov, NCT03132636, and is no longer recruiting new participants.FINDINGS: Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8-18). An objective response per independent central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including two partial responses that emerged at tumour assessments before the data cutoff and were confirmed by tumour assessments done subsequent to the data cutoff. The best overall response was five (6%) patients with a complete response and 21 (25%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 40 (48%) of 84 patients; the most common were hypertension (four [5%] of 84 patients) and colitis (four [5%]). Serious treatment-emergent adverse events occurred in 29 (35%) of 84 patients. There were no treatment-related deaths.INTERPRETATION: Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy.FUNDING: Regeneron Pharmaceuticals and Sanofi.

  View details for DOI 10.1016/S1470-2045(21)00126-1

  View details for PubMedID 34000246

• Association of ruxolitinib with NMSCs risk in patients with polycythemia vera and myelofibrosis Lin, J., Li, S., Li, S., Kiamanesh, E., Aasi, S., Kwong, B., Chang, A. ELSEVIER SCIENCE INC. 2021: S43

  View details for Web of Science ID 000641872800241

• A rare case of Wohlfahrtiimonas chitiniclastica infection in California Leeolou, M. C., Perrault, D. P., Sivaraj, D., Trotsyuk, A. A., Padmanabhan, J., Gurtner, G. C. JAAD case reports. 2021 ; Case Report (Volume 17): 55-57
• An exploratory, open-label study of secukinumab in patients with moderate to severe papulopustular rosacea Kumar, A. M., Chiou, A. S., Shih, Y., Li, S., Chang, A. S. MOSBY-ELSEVIER. 2020: AB88

  View details for Web of Science ID 000598634300353

• INTERIM ANALYSIS OF PHASE 2 RESULTS FOR CEMIPLIMAB IN PATIENTS WITH METASTATIC BASAL CELL CARCINOMA (MBCC) WHO PROGRESSED ON OR ARE INTOLERANT TO HEDGEHOG INHIBITORS (HHIS) Lewis, K., Peris, K., Sekulic, A., Stratigos, A., Dunn, L., Eroglu, Z., Chang, A., Migden, M., Li, S., Mohan, K., Coates, E., Okoye, E., Baurain, J., Bechter, O., Hauschild, A., Butler, M., Hernandez-Aya, L., Licitra, L., Neves, R., Ruiz, E., Seebach, F., Weinreich, D., Yancopoulos, G., Lowy, I., Bowler, T., Fury, M. BMJ PUBLISHING GROUP. 2020: A260–A261

  View details for DOI 10.1136/jitc-2020-SITC2020.0428

  View details for Web of Science ID 000616665300416

• 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

• Time to clinically meaningful changes in pain in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab in a phase II clinical trial Migden, M. R., Rischin, D., Hudgens, S., Chen, C., Schmults, C. D., Pavlick, A. C., Guminski, A., Hauschild, A., Chen, Z., Mastey, V., Bury, D., Chang, A. S., Rabinowits, G., Ibrahim, S. F., Fury, M. G., Li, S., Sasane, M. ELSEVIER. 2020: S738

  View details for DOI 10.1016/j.annonc.2020.08.1211

  View details for Web of Science ID 000573469101375

• Primary analysis of phase II results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs) Stratigos, A. J., Sekulic, A., Peris, K., Bechter, O., Dutriaux, C., Kaatz, M., Lewis, K. D., Basset-Seguin, N., Chang, A. S., Dalle, S., Fernandez-Orland, A., Licitra, L., Robert, C., Ulrich, C., Hauschild, A., Migden, M. R., Dummer, R., Li, S., Bowler, T., Fury, M. G. ELSEVIER. 2020: S1175–S1176

  View details for DOI 10.1016/j.annonc.2020.08.2277

  View details for Web of Science ID 000573469102675

• Adjuvant pembrolizumab or placebo in patients with high-risk, locally advanced cutaneous squamous cell carcinoma: Phase 3 KEYNOTE-630 Chang, A. S., Daniels, G. A., Cohen, E. E., Ge, J., Gumuscu, B., Swaby, R. F., Geiger, J. L. AMER ASSOC CANCER RESEARCH. 2020

  View details for DOI 10.1158/1538-7445.AM2020-LB-138

  View details for Web of Science ID 000590059302266

• 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

• A phase I study of CX-4945 administered orally twice daily to patients with advanced basal cell carcinoma. Eroglu, Z., Cowey, C., Soong, J., McCormick, D., Fan, P., Chen, J., Elgendy, M., Jang, S., Chang, A. S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368309006

• 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

• 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

• 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

• 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. n., Migden, M. R., Lim, A. M., Schmults, C. D., Khushalani, N. I., Hughes, B. G., Schadendorf, D. n., Dunn, L. A., Hernandez-Aya, L. n., Chang, A. L., Modi, B. n., Hauschild, A. n., Ulrich, C. n., Eigentler, T. n., Stein, B. n., Pavlick, A. C., Geiger, J. L., Gutzmer, R. n., Alam, M. n., Okoye, E. n., Mathias, M. n., Jankovic, V. n., Stankevich, E. n., Booth, J. n., Li, S. n., Lowy, I. n., Fury, M. G., Guminski, A. n. 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

• Pathophysiology of Basal Cell Carcinoma and Its Associated Genetic Syndromes BASAL CELL CARCINOMA: ADVANCES IN TREATMENT AND RESEARCH Chang, A. S., Migden, M. R., Chen, L., Silapunt, S. 2020: 19-23

  View details for DOI 10.1007/978-3-030-26887-9_2

  View details for Web of Science ID 000664361100003

• Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study British Journal of Dermatology Dummer, R., Guminski, A., Gutzmer, R., Lear, J. T., Lewis, K. D., Chang, A. S., Combemale, P., Dirix, L., Kaatz, M., Kudchadkar, R., Loquai, C., Plummer, R., Schulze, H., Stratigos, A. J., Trefzer, U., Squitteri, N., Migden, M. R. 2020; 182 (6): 1369-1378

  View details for DOI 10.1111/bjd.18552

• Paired Transcriptomic and Proteomic Analysis Implicates IL-1β in the Pathogenesis of Papulopustular Rosacea Explants. The Journal of investigative dermatology Harden, J. L., Shih, Y. H., Xu, J. n., Li, R. n., Rajendran, D. n., Hofland, H. n., 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-1β as a potential central mediator to PPR pathogenesis. In support of this, stimulation of NL explants with IL-1β 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-1β in driving inflammation in PPR.

  View details for DOI 10.1016/j.jid.2020.08.013

  View details for PubMedID 32941918

• 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. n., Guan, L. n., Zhao, L. n., Palli, M. A., Horn, T. D., Dudek, A. Z., McTavish, H. n. 2020

  View details for DOI 10.1016/j.jaad.2020.04.021

  View details for PubMedID 32289388

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Clonal replacement of tumor-specific T cells following PD-1 blockade. Nature medicine Yost, K. E., Satpathy, A. T., Wells, D. K., Qi, Y. n., Wang, C. n., Kageyama, R. n., McNamara, K. L., Granja, J. M., Sarin, K. Y., Brown, R. A., Gupta, R. K., Curtis, C. n., 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

• Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing. Nature Mahmoudi, S. n., Mancini, E. n., Xu, L. n., Moore, A. n., Jahanbani, F. n., Hebestreit, K. n., Srinivasan, R. n., Li, X. n., Devarajan, K. n., Prélot, L. n., Ang, C. E., Shibuya, Y. n., Benayoun, B. A., Chang, A. L., Wernig, M. n., Wysocka, J. n., Longaker, M. T., Snyder, M. P., Brunet, A. n. 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

• 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

• 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. n., Meschi, F. n., McDermott, G. P., Olsen, B. N., Mumbach, M. R., Pierce, S. E., Corces, M. R., Shah, P. n., Bell, J. C., Jhutty, D. n., Nemec, C. M., Wang, J. n., Wang, L. n., Yin, Y. n., 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

• Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma Journal of INVESTIGATIVE DERMATOLOGY | Original Article | Carcinogenesis/Tumorigenesis Chiang, A., Tan, C. Z., Kuonen, F., Hodgkinson, L. M., Chiang, F., Cho, R. J., South, A. P., Tang, J. Y., Chang, A. S., Rieger, K. E., Oro, A. E., Sarin, K. Y. 2019; 139 (11): 2263-2271. E5

  View details for DOI 10.1016/j.jid.2019.03.1163

• 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

• 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

• 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

• 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

• Hedgehog Pathway Inhibitors as Neoadjuvant Therapy for Orbital/Periorbital Basal Cell Carcinoma Chandramohan, A., Nair, A., Chang, A. L., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932806203

• 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

• 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 DOI 10.1056/NEJMoa1805131

  View details for PubMedID 29863979

• 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

• 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

• 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

• 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

• 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

• 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

• 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 DOI 10.1016/j.ctrv.2017.12.009

  View details for PubMedID 29407368

• 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): 372-381

  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-naïve 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 PubMedID 28846163

  View details for PubMedCentralID PMC5873455

• 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

• 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. n., Chang, A. L. 2018; 4 (3): 248–50

  View details for PubMedID 29687062

  View details for PubMedCentralID PMC5909484

• 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): 156-166

  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

  View details for PubMedID 29089181

• Old fibroblasts secrete inflammatory cytokines that drive variability in reprogramming efficiency and may affect wound healing between old individuals (Preprint) bioRxiv, THE PREPRINT SERVER FOR BIOLOGY Mahmoudi, S., Mancini, E., Moore, A., Xu, L., Jahanbani, F., Hebestreit, K., Srinivisan, R., Li, X., Devarajan, K., Prelot, L., Ang, C. E., Shibuya, Y., Benayoun, B. A., Chang, A. S., Wernig, M., Wysocka, J. T., Longaker, M. T., Snyder, M. P., Brunet, A. 2018

  View details for DOI 10.1101/448431

• 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. n., Jeng, M. n., Patel, R. n., Van der Bokke, L. n., Pague, A. n., Brotherton, R. n., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S. n., Sarin, K. n., Colevas, A. D. 2018

  View details for PubMedID 30145186

• 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

• 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): 1749-1751

  View details for DOI 10.1111/bjd.15225

  View details for PubMedID 27943239

  View details for PubMedCentralID PMC5813161

• 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 DOI 10.1111/bjd.15508

  View details for PubMedID 28369780

• 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

• 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

• 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

• 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

• Genetic drivers of basosquamous carcinoma Chiang, A., Tan, C., Rieger, K., Cho, R., Chang, A. S., Tang, J. Y., Oro, A., Sarin, K. Y. ELSEVIER SCIENCE INC. 2017: S18

  View details for DOI 10.1016/j.jid.2017.02.119

  View details for Web of Science ID 000406862400105

• 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

• Reversible cutaneous side effects of vismodegib treatment. Cutis Kwong, B. n., Danial, C. n., Liu, A. n., Chun, K. A., Chang, A. L. 2017; 99 (3): E19–E20

  View details for PubMedID 28398426

• 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): 76118-76124

  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 PubMedID 27764798

  View details for PubMedCentralID PMC5342800

• 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

• Efficacy and safety of sonidegib in patients (pts) with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC): BOLT 30-month analysis. Dummer, R., Migden, M., Guminski, A., Gutzmer, R., Kudchadkar, R., Lewis, K. D., Dirix, L., Combemale, P., Trefzer, U., Loquai, C., Kaatz, M., Chang, A. S., Stratigos, A., Plummer, E. R., Mone, M., Castro, H., Yi, T., Sellami, D. B., Lear, J. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.9538

  View details for Web of Science ID 000404711507160

• 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

• 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

• 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, Hüls 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

• 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

• 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 < .001), indicating increased risk of developing a non-BCC malignancy. Most non-BCC malignancies were cutaneous squamous cell carcinomas, with a hazard ratio of 8.12 (95% CI, 3.89-16.97; P < .001), accounting for age and basal cell nevus syndrome status. There was no significant increase in other cancers.Increased risk for cutaneous squamous cell carcinomas after vismodegib therapy highlights the importance of continued skin surveillance after initiation of this therapy.

  View details for DOI 10.1001/jamadermatol.2015.4330

  View details for PubMedID 26914338

• 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

• 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 < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients.Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing. Continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response.

  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 < 0.01). In a multivariate analysis of age-matched data, individuals with CUES in the lowest quartile were less likely to develop skin cancer compared to those in the highest quartile. In reliability testing among 19 volunteers, the 2-week intra-class correlation coefficient for CUES was 0.94. We have provided the programming code for this tool as well as the tool itself via open access.CUES is a useable and comprehensive tool to better estimate lifetime ultraviolet exposure, so that individuals with higher levels of exposure may be identified for counseling on photo-protective measures.

  View details for DOI 10.1186/s12895-016-0038-1

  View details for PubMedID 26790927

  View details for PubMedCentralID PMC4721109

• A Case Report of Unresectable Cutaneous Squamous Cell Carcinoma Responsive to Pembrolizumab, a Programmed Cell Death Protein 1 Inhibitor Chang, A. S., Kim, J., Luciano, R., Sullivan-Chang, L., Colevas, A. D. JAMA Dermatology. 2016 ; Observation (Volume 152, Issue 1): 106-108
• Major Changes in Skin Function in the Elderly and Their Contributions to Common Clinical Challenges Textbook of Aging Skin edited by Farage, M. A., Miller, K. W., Maibach, H. I. Springer Berlin, Heidelberg. 2016; 2: 43-53

  View details for DOI 10.1007/978-3-662-47398-6

• Genetic Basis of Healthy Skin Aging Textbook of Aging Skin edited by Farage, M. A., Miller, K. W., Maibach, H. I. Springer Berlin, Heidelberg. 2016; 2: 1525-1528

  View details for DOI 10.1007/978-3-662-47398-6

• 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

• 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

• 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

• 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

• 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

• 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

• 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): 285-93

  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 DOI 10.1016/j.jaad.2015.04.006

  View details for PubMedID 25956658

• 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 : 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 DOI 10.1158/1078-0432.CCR-14-3180

  View details for PubMedID 25792568

• 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

• 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

• 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

• 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

• 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

• 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-ι/λ 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

• Advances in Geriatric Dermatology edited by Chang, A. S. Springer International Publishing. 2015

  View details for DOI 10.1007/978-3-319-18380-0

• 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

• Invited Commentary on Dermatological disease in the older age group: a cross-sectional study in aged care facilities British Medical Journal (BMJ) Publishing Group Limited Deo, M. S., Kerse, N., Vandal, A. C., Jarrett, P. 2015; 5 (12): e009941

  View details for DOI 10.1136/bmjopen-2015-009941

• 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

• 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

• 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

• 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 DOI 10.1001/jamadermatol.2013.8744

  View details for PubMedID 24898076

• 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

• A useable and comprehensive tool to estimate cumulative lifetime ultraviolet exposure Li, A., Chang, A. S., Zhu, G. A. MOSBY-ELSEVIER. 2014: AB153

  View details for Web of Science ID 000360583900604

• 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 α-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

• 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 DOI 10.1007/s13671-014-0069-y

  View details for PubMedID 24587976

  View details for PubMedCentralID PMC3931971

• 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

• Special Patient Populations MODERATE TO SEVERE PSORIASIS, 4TH EDITION Butler, D. C., Kamangar, F., Levin, E. C., Koo, J. M., Chang, A. S., Koo, J. Y., Levin, E. C., Leon, A., Wu, J. J., Gottlieb, A. B. 2014: 335-348

  View details for Web of Science ID 000355629600020

• 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 < 0.0001), marital status (p = 0.02), family history of skin cancer (p = 0.03) and generation in the United States (p = 0.02) were significant predictors of the primary outcome of "ever had skin checked by a dermatologist".Identification of patient-related factors that associate with dermatology clinic visits in Asian-Americans is important so that this potential gap in dermatologic care can be better addressed through future studies.

  View details for DOI 10.1186/1471-5945-14-13

  View details for PubMedID 25085260

• Dermatologic Clinical Trials: A Practical Approach Clinical Dermatology Trials 101: A Primer for Dermatologists Mohan, S., Chang, A. S. Springer International Publishing. 2014; 1st: 47-58

  View details for DOI 10.1007/978-3-319-09027-6_3

• 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

• Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors CLINICAL CANCER RESEARCH Jimeno, A., Weiss, G. J., Miller, W. H., Gettinger, S., Eigl, B. C., Chang, A. S., Dunbar, J., Devens, S., Faia, K., Skliris, G., Kutok, J., Lewis, K. D., Tibes, R., Sharfman, W. H., Ross, R. W., Rudin, C. M. 2013; 19 (10): 2766–74

  Abstract

  To conduct a first-in-human phase I study to determine the dose-limiting toxicities (DLT), characterize the pharmacokinetic profile, and document the antitumor activity of IPI-926, a new chemical entity that inhibits the Hedgehog pathway (HhP).Patients with solid tumors refractory to standard therapy were given IPI-926 once daily (QD) by mouth in 28-day cycles. The starting dose was 20 mg, and an accelerated titration schedule was used until standard 3 + 3 dose-escalation cohorts were implemented. Pharmacokinetics were evaluated on day -7 and day 22 of cycle 1.Ninety-four patients (32F, 62M; ages, 39-87) received doses ranging from 20 to 210 mg QD. Dose levels up to and including 160 mg administered QD were well tolerated. Toxicities consisted of reversible elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin, fatigue, nausea, alopecia, and muscle spasms. IPI-926 was not associated with hematologic toxicity. IPI-926 pharmacokinetics were characterized by a slow absorption (T(max) = 2-8 hours) and a terminal half-life (t(1/2)) between 20 and 40 hours, supporting QD dosing. Of those HhP inhibitor-naïve patients with basal cell carcinoma (BCC) who received more than one dose of IPI-926 and had a follow-up clinical or Response Evaluation Criteria in Solid Tumors (RECIST) assessment, nearly a third (8 of 28 patients) showed a response to IPI-926 at doses ≥130 mg.IPI-926 was well tolerated up to 160 mg QD within 28-day cycles, which was established as the recommended phase II dose and schedule for this agent. Single-agent activity of IPI-926 was observed in HhP inhibitor-naïve patients with BCC.

  View details for DOI 10.1158/1078-0432.CCR-12-3654

  View details for Web of Science ID 000318911600020

  View details for PubMedID 23575478

  View details for PubMedCentralID PMC3694426

• 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

• 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

• 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

• 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

• Geriatric dermatology: Part II. Risk factors and cutaneous signs of elder mistreatment for the dermatologist Journal of the American Academy of Dermatology Chang, A. S., Wong, J. W., Endo, J. O., Norman, R. A. 2013; 68 (4): 533. E1-533.E10

  View details for DOI 10.1016/j.jaad.2013.01.001

• 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

• 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

• 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

• 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

• 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

• 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

• 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, R. C., Cheng, M. Y., Chun, K. A., Gorell, E. S., Munoz, C. A., Kern, D. G., Wood, S. M., Knaggs, H. E., Beebe, K. D., Chang, A. S. 2012; 4 (2)

  View details for DOI 10.1186/gm313

• A Little Known but Potentially Life-threatening Association of Bullous Pemphigoid and Acquired Hemophilia: Case Report and Review of the Literature Nguyen, C., Gordan, J. S., Chang, A. S. Journal of Clinical & Experimental Dermatology Research. 2012 ; Commentary (ISSN:2155-9554): 1-3
• More than just a coincidence: Herpes zoster and acne rosacea appearing together as Wolf's isotopic response in an Asian female Fijalkowski, N., Wysong, A., Khuu, P., Chang, A. S. International Journal of Case Reports and Images. 2012 ; Case Report (Volume 3, Issue 2): 24-27
• 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, A. S. 2012; 2012 (1): 7

  View details for DOI 10.1155/2012/767861

• 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

• 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

• 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

• A case of Cinderella: erythema dyschromicum perstans (ashy dermatosis or dermatosis cinecienta) Munoz, C., Chang, A. S. SKINmed: Dermatology for the Clinician (Published by Pulse Marketing and Communications, LLC.). 2011 ; Case Studies (Volume 9, Issue 1): 63-64
• 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): 230-6

  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 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

• 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

• Adoption of Western Culture by Californian Asian Americans: Attitudes and Practices Promoting Sun Exposure Gorell, E., Lee, C., Munoz, C., Chang, A. S. JAMA Dermatology. 2009 ; Comparative Study (Volume 145, Issue 5): 552-556
• 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

• Academic dermatology realities: Results from a 2002 survey of AADA members Chang, A. L., Kimball, A., Resneck, J. MOSBY, INC. 2005: P99

  View details for Web of Science ID 000227632400392

• 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 REPRODUCTION Sagoskin, A. W., Lessey, B. A., Mottla, G. L., Richter, K. S., Chetkowski, R. J., Chang, A. S., Levy, M. J., Stillman, R. J. 2003; 18 (12): 2634-2637

  Abstract

  Studies carried out over the past 10 years have suggested that hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges and patent contralateral tubes.This multi-centre, retrospective study included 25 infertility patients with known unilateral hydrosalpinges with a patent contralateral Fallopian tube. Laparoscopic treatment of unilateral hydrosalpinges by either salpingectomy or tubal occlusion was performed in each patient. Rates of subsequently observed spontaneous pregnancy, and time to pregnancy, are reported.The average duration of infertility in these patients was 3 years with a range of 1-10 years. Following laparoscopic surgical treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all without IVF treatment. Pregnancies occurred in an average of 5.6 months with a range of 1-21 months. There were no ectopic pregnancies in the study population.Selected patients with unilateral hydrosalpinges and a patent contralateral Fallopian tube may exhibit increased cycle fecundity after salpingectomy or proximal tubal occlusion of the affected tube and conceive without the need for IVF.

  View details for DOI 10.1093/humrep/deg509

  View details for Web of Science ID 000187224700026

  View details for PubMedID 14645184

• Obstetric attending physician characteristics and their impact on vacuum and forceps delivery rates: University of California at San Francisco experience from 1977 to 1999 Chang, A. L., Noah, M. S., Laros, R. K. MOSBY, INC. 2002: 1299-1303

  Abstract

  The objective of our study was to determine the impact of obstetric attending physician characteristics (eg, region of previous residency training, sex, year of graduation from residency) on the rates of vacuum and forceps delivery at our institution.The analysis was based on 19,897 vaginal deliveries that were performed by 171 attending physicians and 160 resident physicians between 1977 and 1999 at the University of California at San Francisco Medical Center. Z -tests and multivariate logistic regression were performed on a perinatal database that contained standard obstetric variables.Male attending physicians had a higher percentage of forceps deliveries compared with female attending physicians (11.1% vs 6.6%; P <.001); female attending physicians had a higher percentage of vacuum deliveries compared with male attending physicians (9.8% vs 5.1%; P <.001). However, multivariate regression analysis revealed that only the year in which the procedure was performed affected both the forceps and vacuum delivery rates (P <.041). The region of previous residency training of the attending physician affected the vacuum delivery rate (P <.0001) but not the forceps delivery rate (P >.06) in multivariate logistic regression analysis. Factors such as the sex of the obstetric attending physician, the sex of the resident, and the year of graduation from residency for the obstetric attending physician did not have a significant impact on the forceps or vacuum delivery rates (all P >.05).Our study is the first to report that the apparent gender differences in forceps and vacuum delivery rates among obstetric attending physicians was due to the year in which the procedure was performed and not due to sex per se. We also found that the region of previous residency training for the obstetric attending physician significantly influenced the vacuum delivery rate.

  View details for DOI 10.1067/mob.2002.123735

  View details for Web of Science ID 000176385000050

  View details for PubMedID 12066112

• Talin and vinculin play distinct roles in filopodial motility in the neuronal growth cone Journal of Cell Biology (JCB) Sydor, A. M., Su A.L., Wang, F. S., Jay, D. G. 1996; 134 (5): 1197-1207

  Abstract

  Filopodial motility is critical for many biological processes, particularly for axon guidance. This motility is based on altering the F-actin-based cytoskeleton, but the mechanisms of how this occurs and the actin-associated proteins that function in this process remain unclear. We investigated two of these proteins found in filopodia, talin and vinculin, by inactivating them in subregions of chick dorsal root ganglia neuronal growth cones and by observing subsequent behavior by video-enhanced microscopy and quantitative morphometry. Microscale chromophore-assisted laser inactivation of talin resulted in the temporary cessation of filopodial extension and retraction. Inactivation of vinculin caused an increased incidence of filopodial bending and buckling within the laser spot but had no effect on extension or retraction. These findings show that talin acts in filopodial motility and may couple both extension and retraction to actin dynamics. They also suggest that vinculin is not required for filopodial extension and retraction but plays a role in the structural integrity of filopodia.

  View details for DOI 10.1083/jcb.134.5.1197

  View details for PubMedCentralID PMC2120982

• Chromophore-assisted laser inactivation of patched protein switches cell fate in the larval visual system of Drosophila. Proceedings of the National Academy of Sciences of the United States of America (PNAS) Schmucker, D., Su A.L., Beermann, A., Jay, D. G. 1994; 91 (7): 2664-2668

  Abstract

  The Drosophila segment-polarity gene patched (ptc) is an integral component of the segmentation gene cascade acting in the early embryo. At later stages of embryogenesis, ptc is expressed in the primordia of epithelial placodes of a specific portion of the brain, the optic lobes. Mutant analysis shows that the lack of ptc activity alters the fate of optic-lobe primordia precursors. In ptc mutants they give rise to supernumerary neurons in the larval light-sensory system, termed Bolwig organ, which is derived from precursor cells next to the optic-lobe anlagen. We specifically eliminated ptc protein by chromophore-assisted laser inactivation (CALI) in late wild-type embryos. Such embryos show a normal segment pattern, but they develop phenocopies equivalent to the phenotype of ptc mutant Bolwig organs. Our results demonstrate that the CALI technique can be applied to separate genetic functions at different developmental stages of a living organism and that the segment-polarity gene ptc is redeployed to functionally discriminate between distinct developmental pathways in adjacent pools of precursor cells.

  View details for DOI 10.1073/pnas.91.7.2664

  View details for PubMedCentralID PMC43430