Medicine and Health Sciences Commons^™

Phase Ib/Ii Study Of Lacnotuzumab In Combination With Spartalizumab In Patients With Advanced Malignancies, Jibran Ahmed, Bettzy Stephen, Yali Yang, Evan Kwiatkowski, Chinenye Lynette Ejezie, Shubham Pant

Journal Articles

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance.

METHODS: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The …

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

Advances In Melanoma: Epidemiology, Diagnosis, And Prognosis, Shayan Waseh, Jason B. Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by …

A Multicenter Study Validates The Who 2022 Classification For Conjunctival Melanocytic Intraepithelial Lesions With Clinical And Prognostic Relevance, Hardeep Singh Mudhar, Yamini Krishna, Simon Cross, Claudia Auw-Haedrich, Raymond Barnhill, Svetlana Cherepanoff, Ralph Eagle, James Farmer, Robert Folberg, Hans Grossniklaus, Martina C. Herwig-Carl, Martin Hyrcza, Sandra Lassalle, Karin U. Loeffler, Alexandre Moulin, Tatyana Milman, Robert M. Verdijk, Steffen Heegaard, Sarah E. Coupland

Wills Eye Hospital Papers

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology …

Intrinsic Disorder In Prame And Its Role In Uveal Melanoma, Michael Antonietti, David J. Taylor Gonzalez, Mak Djulbegovic, Guy W. Dayhoff, Vladimir N. Uversky, Carol L. Shields, Carol L. Karp

Wills Eye Hospital Papers

Introduction

The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME( +) Class 1 UM.

Methods

A bioinformatics study to characterize PRAME’s propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the …

First-Line, Fixed-Duration Nivolumab Plus Ipilimumab Followed By Nivolumab In Clinically Diverse Patient Populations With Unresectable Stage Iii Or Iv Melanoma: Checkmate 401, Reinhard Dummer, Pippa Corrie, Ralf Gutzmer, Tarek M. Meniawy, Michele Del Vecchio, Céleste Lebbé, Michele Guida, Caroline Dutriaux, Brigitte Dreno, Nicolas Meyer, Pier F. Ferrucci, Stéphane Dalle, Muhammad A. Khattak, Jean-Jacques Grob, Karen Briscoe, James Larkin, Sandrine Mansard, Thierry Lesimple, Massimo Guidoboni, Silvia Sabatini, Erika Richtig, Rudolf Herbst, Maurice Lobo, Margarita Askelson, Paolo A. Ascierto, Michele Maio

Research outputs 2022 to 2026

PURPOSE: To address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma. METHODS: Treatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for ≤ 24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). …

Conditional Metastasis Of Uveal Melanoma In 8091 Patients Over Half-Century (51 Years) By Age Group: Assessing The Entire Population And The Extremes Of Age, Carol L. Shields, Annika Samuelson, Glenn Oh, Joseph D. Desimone, Zaynab Sajjadi, Zeynep Bas, Nicholas E Kalafatis, Sara E. Lally, Jerry A. Shields, Philip W. Dockery

Wills Eye Hospital Papers

PURPOSE: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age).

METHODS: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific …

Tebentafusp In Combination With Durvalumab And/Or Tremelimumab In Patients With Metastatic Cutaneous Melanoma: A Phase 1 Study, Omid Hamid, Jessica C. Hassel, Alexander N. Shoushtari, Friedegund Meier, Todd M. Bauer, April K.S. Salama, John M. Kirkwood, Paolo A. Ascierto, Paul C. Lorigan, Cornelia Mauch, Marlana Orloff, Thomas R. Jeffry Evans, Chris Holland, Ramakrishna Edukulla, Shaad E. Abedin, Mark R. Middleton

Department of Medical Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority …

Selective Immune Suppression Using Interleukin-6 Receptor Inhibitors For Management Of Immune-Related Adverse Events, Faisal Fa'ak, Maryam Buni, Adewunmi Falohun, Huifang Lu, Juhee Song, Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Muhammad Osama Awiwi, Nourel Hoda Tahon, Khaled M Elsayes, Kaysia Ludford, Emma J Montazari, Julia Chernis, Maya Dimitrova, Sabina Sandigursky, Jeffrey A Sparks, Osama Abu-Shawer, Osama Rahma, Uma Thanarajasingam, Ashley M Zeman, Rafee Talukder, Namrata Singh, Sarah H Chung, Petros Grivas, May Daher, Ala Abudayyeh, Iman Osman, Jeffrey Weber, Jean H Tayar, Maria E Suarez-Almazor, Noha Abdel-Wahab, Adi Diab

Journal Articles

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.

METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.

RESULTS: We identified a total of 92 patients …

High Expression Of Talin-1 Is Associated With Tumor Progression And Recurrence In Melanoma Skin Cancer Patients., Yasaman Rezaie, Fahimeh Fattahi, Baharnaz Mashinchi, Kambiz Kamyab Hesari, Sahar Montazeri, Elham Kalantari, Zahra Madjd, Leili Saeednejad Zanjani

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors.

METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed.

RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels …

Inhibitors Of Histone Deacetylase And Mcl-1 Synergistically Reduce Proliferation In Malignant Melanoma, Mehrnoosh Ghafouri, Chester Gauss, Yue Xi Phd, William Azkoul Ii Md, Abby Knudsen, Jordan Zuckerman, Sharon K. Michelhaugh Phd, Sandeep Mittal Md, Andrew M. Fribley Phd

Medical Student Research Symposium

Melanoma is a skin cancer that arises in melanocytes; it is the fifth most common cancer in the United States with approximately 100,000 new cases per year. Current treatments for malignant melanoma are surgical excision, radiation therapy and systemic therapy; however, the five-year survival rate for patients with stage IV is 29.8%. There is an urgent unmet clinical need to investigate novel treatments for these patients. Panobinostat is an orally available histone deacetylase inhibitor used in several hematologic malignancies, but it was ineffective as a single agent against melanoma in Phase 1. To address the insufficiency of options for melanoma …

Racial Differences In Perceived Risk And Sunscreen Usage, Rebecca Fliorent, Alicia Podwojniak, Lianne Adolphe, Katharine Milani

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Background Although White individuals have higher incidence of melanoma, clinical outcomes are worse among patients with skin of color. This disparity arises from delayed diagnoses and treatment that are largely due to clinical and sociodemographic factors. Investigating this discrepancy is crucial to decrease melanoma-related mortality rates in minority communities. A survey was used to investigate the presence of racial disparities in perceived sun exposure risks and behaviors. Methods A survey consisting of 16 questions was deployed via social media to assess skin health knowledge. Over 350 responses were recorded, and the extracted data were analyzed using statistical software. Results Of …

Skin Lesion Segmentation In Dermoscopic Images With Noisy Data, Norsang Lama, Jason Hagerty, Anand Nambisan, Ronald Joe Stanley, William Van Stoecker

Electrical and Computer Engineering Faculty Research & Creative Works

We Propose a Deep Learning Approach to Segment the Skin Lesion in Dermoscopic Images. the Proposed Network Architecture Uses a Pretrained Efficient Net Model in the Encoder and Squeeze-And-Excitation Residual Structures in the Decoder. We Applied This Approach on the Publicly Available International Skin Imaging Collaboration (ISIC) 2017 Challenge Skin Lesion Segmentation Dataset. This Benchmark Dataset Has Been Widely Used in Previous Studies. We Observed Many Inaccurate or Noisy Ground Truth Labels. to Reduce Noisy Data, We Manually Sorted All Ground Truth Labels into Three Categories — Good, Mildly Noisy, and Noisy Labels. Furthermore, We Investigated the Effect of Such …

Efficacy And Safety Of Lifileucel, A One-Time Autologous Tumor-Infiltrating Lymphocyte (Til) Cell Therapy, In Patients With Advanced Melanoma After Progression On Immune Checkpoint Inhibitors And Targeted Therapies: Pooled Analysis Of Consecutive Cohorts Of The C-144-01 Study, Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik

Department of Medical Oncology Faculty Papers

Background: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.

Methods: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Adjuvant Pembrolizumab Versus Placebo In Resected High-Risk Stage Ii Melanoma: Health-Related Quality Of Life From The Randomized Phase 3 Keynote-716 Study, Muhammad A. Khattak, Jason J. Luke, Georgina V. Long, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Caroline Robert, Jean-Jacques Grob, Luis De La Cruz Merino, Michele Del Vecchio, Francesco Spagnolo, Jacek Mackiewicz, Vanna Chiarion-Sileni, Matteo S. Carlino, Peter Mohr, Federica De Galitiis, Merrick I. Ross, Zeynep Eroglu, Ke Chen, Ruixuan Jiang, Mizuho Fukunaga-Kalabis, Clemens Krepler, Alexander M. M. Eggermont, John M. Kirkwood

Research outputs 2022 to 2026

Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) versus placebo in resected stage IIB and IIC melanoma in the phase 3 KEYNOTE-716 study. Health-related quality of life (HRQoL) results are reported. Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg (2 mg/kg, patients ≥ 12 to < 18 years) Q3W or placebo for ≤ 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal. Change from baseline in EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) was a prespecified exploratory end point. Change in EORTC QLQ-C30 functioning, symptom, and single-item scales, and EQ-5D-5L visual analog scale (VAS) were also summarized. Primary analyses were performed at week 48 to ensure adequate completion/compliance. The HRQoL population comprised patients who received ≥ 1 dose of treatment and completed ≥ 1 assessment. Results: The HRQoL population included 969 patients (pembrolizumab, n = 483; placebo, n = 486). Compliance at week 48 was ≥ 80 % for both instruments. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores were stable from baseline to week 48 in both arms, with no clinically meaningful decline observed. Scores did not differ significantly between pembrolizumab and placebo. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores remained stable through week 96 in both arms. Conclusions: HRQoL was stable with adjuvant pembrolizumab, with no clinically meaningful decline observed. Change from baseline in HRQoL was similar between arms. These results, in conjunction with the improved RFS and manageable safety previously reported, support the use of adjuvant pembrolizumab for high-risk stage II melanoma.

Keynote - D36: Personalized Immunotherapy With A Neoepitope Vaccine, Evx-01 And Pembrolizumab In Advanced Melanoma, Georgina V. Long, Pier Francesco Ferrucci, Adnan Khattak, Tarek M. Meniawy, Patrick Alexander Ott, Michael Chisamore, Thomas Trolle, Agon Hyseni, Erik Heegaard

Research outputs 2022 to 2026

Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall …

A Genome-Wide Screen Identifies Pdpk1 As A Target To Enhance The Efficacy Of Mek1/2 Inhibitors, Weijia Cai, Nicole A. Wilski, Timothy J. Purwin, Megane Vernon, Manoela Tiago, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Melanomas frequently harbor activating NRAS mutations. However, limited advance has been made in developing targeted therapy options for NRAS mutant melanoma patients. MEK inhibitors (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of Phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacological and molecular approaches. Combined PDPK1 inhibitors (PDPK1i) with MEKi suppressed NRAS mutant xenograft growth and induced gasdermin E-associated pyroptosis. In an immune-competent …

Advanced-Stage Melanoma At Presentation Following The Peak Of The Pandemic: A Covid-19 Cancer Canary In A Coal Mine, Ryan Lamm, Md, Walker Lyons, Md, Winnie So, Rn, Alliric I. Willis, Md, Facs, Msph

Department of Surgery Faculty Papers

Background: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline.

Methods: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables …

Finding The Right Scope: Dermoscopy For Primary Care, Peggy Cyr, Elizabeth Seiverling

MaineHealth Maine Medical Center

Background

• Primary care physicians (PCPs) frequently address skin concerns and perform clinical skin examinations1

• For PCPs, the use of dermoscopy has been shown to increase the sensitivity for skin cancer diagnosis compared to unassisted examinations2,3

• Prior to this study, no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy

Objectives

• To develop an expert opinion consensus statement on 2 proficiency standards for PCPs using dermoscopy

Impact Of Dermoscopy Training For Pcps On Nnb To Detect Melanoma, Madeline Prentiss, Kathryn Stevens, Henry Stoddard, Peggy Cyr, Laura Houk, Hadjh Ahrns, Elizabeth Seiverling

MaineHealth Maine Medical Center

The goal of this project was to analyze the impact of dermoscopy training on the number of melanocytic nevi needed to biopsy (NNB) to detect a melanoma in the primary care setting .

Pediatric Dermatology Econsult Program With Dermoscopy: Sub Analysis Of Infantile Hemangiomas, Peggy R. Cyr, Madeline Prentiss, Hadjh Ahrns, Abby Markham, Elizabeth V Seiverling

MaineHealth Maine Medical Center

Here we present an analysis of pediatric dermatology eConsults with emphasis on dermoscopy utilization and the impact on eConsult on infantile hemangiomas (IH) management.

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with …

Is Timing Of Steroid Exposure Prior To Immune Checkpoint Inhibitor Initiation Associated With Treatment Outcomes In Melanoma? A Population-Based Study, Nikita Nikita, Joshua Banks, Scott W. Keith, Andrew Song, Jennifer M. Johnson, Melissa Wilson, Swapnil Sharma, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after …

Mapping Melanoma Risk And Locating High-Need Regions For Dermoscopy And Skin Biopsy Training, Calla Hladky, Madeline Prentiss, Henry Stoddard, Kathryn Stevens, Elizabeth Seiverling, Peg Cyr

MaineHealth Maine Medical Center

Background- Dermoscopy and skin biopsy trainings have been shown to help improve PCPs’ knowledge of and confidence in detecting skin cancer. The goal of this project was to determine where to focus training efforts in order to maximize our impact and reach regions that face the highest burden of melanoma in the state.

Sox10 Requirement For Melanoma Tumor Growth Is Due, In Part, To Immune-Mediated Effects, Sheera Rosenbaum, Manoela Tiago, Signe Caksa, Claudia Capparelli, Timothy J. Purwin, Gaurav Kumar, Mckenna Glasheen, Danielle Pomante, Daniel Kotas, I Chervoneva, A E Aplin

Department of Cancer Biology Faculty Papers

Developmental factors may regulate the expression of immune modulatory proteins in cancer, linking embryonic development and cancer cell immune evasion. This is particularly relevant in melanoma because immune checkpoint inhibitors are commonly used in the clinic. SRY-box transcription factor 10 (SOX10) mediates neural crest development and is required for melanoma cell growth. In this study, we investigate immune-related targets of SOX10 and observe positive regulation of herpesvirus entry mediator (HVEM) and carcinoembryonic-antigen cell-adhesion molecule 1 (CEACAM1). Sox10 knockout reduces tumor growth in vivo, and this effect is exacerbated in immune-competent models. Modulation of CEACAM1 expression but not HVEM elicits modest …

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Karl D Lewis, Robert Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N Markovic, Tawnya Bowles, Omid Hamid, Leonel Hernandez-Aya, Joel Claveau, Sekwon Jang, Prejesh Philips, Shernan G Holtan, Montaser F Shaheen, Brendan Curti, William Schmidt, Marcus O Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, J Thaddeus Beck, Jeffrey B Travers, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, Edward C Mccarron, Vinay Gupta, Deepti Behl, Brent Blumenstein, Joanna J Peterkin

Department of Medical Oncology Faculty Papers

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

Methods: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …

Genomic Data From Nsclc Tumors Reveals Correlation Between Shp-2 Activity And Pd-L1 Expression And Suggests Synergy In Combining Shp-2 And Pd-1/Pd-L1 Inhibitors, Keller J. Toral, Mark A. Wuenschel, Esther P. Black

Pharmaceutical Sciences Faculty Publications

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition …