Medicine and Health Sciences Commons^™

The Effects Of Physical Activity On Cancer Patients Undergoing Treatment With Immune Checkpoint Inhibitors: A Scoping Review, Amy L Shaver, Swapnil Sharma, Nikita Nikita, Daniel S Lefler, Atrayee Basu Mallick, Jennifer Johnson, Meghan Butryn, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Background: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy.

Method: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results.

Results: …

The Effects Of Physical Activity On Cancer Patients Undergoing Treatment With Immune Checkpoint Inhibitors: A Scoping Review., Amy L Shaver, Swapnil Sharma, Nikita Nikita, Daniel S Lefler, Atrayee Basu-Mallick, Jennifer M Johnson, Meghan Butryn, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

BACKGROUND: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy.

METHOD: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results.

RESULTS: …

Ivermectin Induces Apoptosis Of Esophageal Squamous Cell Carcinoma Via Mitochondrial Pathway, Nana Xu, Mengmeng Lu, Jiaxin Wang, Yujia Li, Xiaotian Yang, Xiajie Wei, Jiaoyang Si, Jingru Han, Xiaojuan Yao, Juanmei Zhang, Junqi Liu, Yanming Li, Hushan Yang, Dengke Bao

Department of Medical Oncology Faculty Papers

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.

Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels.

Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, …

Metabolic Pathways And Targets In Chondrosarcoma, Ida Micaily, Megan E Roche, Mohammad Y Ibrahim, Ubaldo E. Martinez-Outshoorn, Atrayee Basu Mallick

Department of Medical Oncology Faculty Papers

Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and …

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Prognostic Values Of G-Protein Mutations In Metastatic Uveal Melanoma, Mizue Terai, Ayako Shimada, I Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B Wedegaertner, Jeffrey L Benovic, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and …

Impact Of Cannabis Use On Least Pain Scores Among African American And White Patients With Cancer Pain: A Moderation Analysis, Salimah H Meghani, Ryan Quinn, Rebecca Ashare, Kristin Levoy, Brooke Worster, Mary Naylor, Jesse Chittams, Martin Cheatle

Department of Medical Oncology Faculty Papers

Introduction: Based on many published reports, African American patients with cancer experience higher pain severity scores and lower pain relief than White patients. This disparity results from undertreatment of pain and is compounded by low adherence to prescribed non-opioid and opioid analgesics among African American patients with cancer. While nearly one in four patients use cannabis to manage cancer-related symptoms, less is known about how cannabis use influences pain relief in this patient population.

Methods: This study is based on preliminary data from an ongoing study of longitudinal outcomes of opioid therapy among African American and White patients with cancer. …

Genetic Landscape And Emerging Therapies In Uveal Melanoma, Rino S Seedor, Marlana Orloff, Takami Sato

Department of Medical Oncology Faculty Papers

Despite successful treatment of primary uveal melanoma, up to 50% of patients will develop systemic metastasis. Metastatic disease portends a poor outcome, and no adjuvant or metastatic therapy has been FDA approved. The genetic landscape of uveal melanoma is unique, providing prognostic and potentially therapeutic insight. In this review, we discuss our current understanding of the molecular and cytogenetic mutations in uveal melanoma, and the importance of obtaining such information. Most of our knowledge is based on primary uveal melanoma and a better understanding of the mutational landscape in metastatic uveal melanoma is needed. Clinical trials targeting certain mutations such …

Establishing A Primary Care Alliance For Conducting Cancer Prevention Clinical Research At Community Sites, Bernard W Parker, Barbara L Mcaneny, Edith P. Mitchell, Ana Maria Lopez, Sandra A Russo, Pamela Maxwell, Leslie G Ford, Worta Mccaskill-Stevens

Department of Medical Oncology Faculty Papers

In September 2020, the National Cancer Institute convened the first PARTNRS Workshop as an initiative to forge partnerships between oncologists, primary care professionals, and non-oncology specialists for promoting patient accrual into cancer prevention trials. This effort is aimed at bringing about more effective accrual methods to generate decisive outcomes in cancer prevention research. The workshop convened to inspire solutions to challenges encountered during the development and implementation of cancer prevention trials. Ultimately, strategies suggested for protocol development might enhance integration of these trials into community settings where a diversity of patients might be accrued. Research Bases (cancer research organizations that …

The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato

Department of Medical Oncology Faculty Papers

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit …

Covid-19 In Patients With Hematologic Malignancies: A Single Center Retrospective Study, Xuejun Wang, Adam Binder, Usama Gergis, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

Initial studies that described the novel coronavirus (COVID-19) reported increased morbidity and mortality in patients with cancer. Of this group, patients with hematologic malignancies (HM) had the highest disease severity and death rates. Subsequent studies have attempted to better describe how COVID-19 affects patients with HM. However, these studies have yielded variable and often contradictory results. We present our single-institution experience with patients with HM who were diagnosed with COVID-19 from March 2020 to March 2021. We report 62 total cases with 10 patients who died during this time. The overall mortality was 16.1%. Mortality during the first two waves …

Tbx15/Mir-152/Kif2c Pathway Regulates Breast Cancer Doxorubicin Resistance Via Promoting Pkm2 Ubiquitination, Cheng-Fei Jiang, Yun-Xia Xie, Ying-Chen Qian, Min Wang, Ling-Zhi Liu, Yong-Qian Shu, Xiao-Ming Bai, Bing-Hua Jiang

Department of Medical Oncology Faculty Papers

Background: Chemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.

Methods: As measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were …

Pd-L1 Quantification Across Tumor Types Using The Reverse Phase Protein Microarray: Implications For Precision Medicine, Elisa Baldelli, K Alex Hodge, Guido Bellezza, Neil J Shah, Guido Gambara, Angelo Sidoni, Martina Mandarano, Chamodya Ruhunusiri, Bryant Dunetz, Maysa Abu-Khalaf, Julia Wulfkuhle, Rosa I Gallagher, Lance Liotta, Johann De Bono, Niven Mehra, Ruth Riisnaes, Antonella Ravaggi, Franco Odicino, Maria Isabella Sereni, Matthew Blackburn, Angela Zupa, Giuseppina Improta, Perry Demsko, Lucio Crino', Vienna Ludovini, Giuseppe Giaccone, Emanuel F Petricoin, Mariaelena Pierobon

Department of Medical Oncology Faculty Papers

BACKGROUND: Anti-programmed cell death protein 1 and programmed cell death ligand 1 (PD-L1) agents are broadly used in first-line and second-line treatment across different tumor types. While immunohistochemistry-based assays are routinely used to assess PD-L1 expression, their clinical utility remains controversial due to the partial predictive value and lack of standardized cut-offs across antibody clones. Using a high throughput immunoassay, the reverse phase protein microarray (RPPA), coupled with a fluorescence-based detection system, this study compared the performance of six anti-PD-L1 antibody clones on 666 tumor samples.

METHODS: PD-L1 expression was measured using five antibody clones (22C3, 28-8, CAL10, E1L3N and …

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 …

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment., Ronald E. Myers, Phd, Dsw, Shailesh M Advani, Pamela Myers, Preethi Selvan Mph Student, Gregory Garber, Msw, Lcsw, Brooke Worster, Md, Neal Flomenberg, Md, Andrew Chapman, Do, Ralph Zinner

Department of Medical Oncology Faculty Papers

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

Gaps In Public Awareness About Brca And Genetic Testing In Prostate Cancer: Social Media Landscape Analysis., Stacy Loeb, Philip Massey, Amy E. Leader, Sameer Thakker, Emily Falge, Sabina Taneja, Nataliya Byrne, Meredith Rose, Matthew Joy, Dawn Walter, Matthew S. Katz, Risa L. Wong, Preethi Selvan, Scott W. Keith, Veda N. Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing, particularly for BRCA1/2, is increasingly important in prostate cancer (PCa) care, with impact on PCa management and hereditary cancer risk. However, the extent of public awareness and online discourse on social media is unknown, and presents opportunities to identify gaps and enhance population awareness and uptake of advances in PCa precision medicine.

OBJECTIVE: The objective of this study was to characterize activity and engagement across multiple social media platforms (Twitter, Facebook, and YouTube) regarding BRCA and genetic testing for PCa compared with breast cancer, which has a long history of public awareness, advocacy, and prominent social media …

Gaps In Public Awareness About Brca And Genetic Testing In Prostate Cancer: Social Media Landscape Analysis, Stacy Loeb, Philip Massey, Amy Leader, Sameer Thakker, Emily Falge, Sabina Taneja, Nataliya Byrne, Meredith Rose, Matthew Joy, Dawn Walter, Matthew S Katz, Risa L Wong, Preethi Selvan, Scott W Keith, Veda N. Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing, particularly for BRCA1/2, is increasingly important in prostate cancer (PCa) care, with impact on PCa management and hereditary cancer risk. However, the extent of public awareness and online discourse on social media is unknown, and presents opportunities to identify gaps and enhance population awareness and uptake of advances in PCa precision medicine.

OBJECTIVE: The objective of this study was to characterize activity and engagement across multiple social media platforms (Twitter, Facebook, and YouTube) regarding BRCA and genetic testing for PCa compared with breast cancer, which has a long history of public awareness, advocacy, and prominent social media …

Debating Frontline Therapy In Chronic Myeloid Leukemia., Xia Bi, Sabarina Ramanathan, Gina Keiffer

Department of Medical Oncology Faculty Papers

No abstract provided.

Reversing The Effects Of Androgen-Deprivation Therapy In Men With Metastatic Castration-Resistant Prostate Cancer, Catherine H Marshall, Jessa Tunacao, Varun Danda, Hua-Ling Tsai, John Barber, Rakhee Gawande, Clifford R Weiss, Samuel R Denmeade, Corinne Joshu

Department of Medical Oncology Faculty Papers

OBJECTIVE: To investigate whether bipolar androgen therapy (BAT), involving rapid cyclic administration of high-dose testosterone, as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) promotes improvements in body composition and associated improvements in lipid profiles and quality of life.

PATIENTS AND METHODS: Men from two completed trials with computed tomography imaging at baseline and after three cycles of BAT were included. Cross-sectional areas of psoas muscle, visceral and subcutaneous fat were measured at the L3 vertebral level. Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire and 36-item short-form health survey were used to assess quality of life.

RESULTS: …

A Retrospective Cohort Study Of Myosteatosis And Quality Of Life In Head And Neck Cancer Patients., Amy L Shaver, Katia Noyes, Heather M Ochs-Balcom, Gregory Wilding, Andrew D Ray, Sung Jun Ma, Mark Farrugia, Anurag K Singh, Mary E Platek

Department of Medical Oncology Faculty Papers

Head and neck cancer (HNC) treatment-related morbidity can be detrimental to quality of life (QOL). Myosteatosis is associated with poor QOL in multiple cancers. If predictive of poor QOL trajectories, myosteatosis would be a tool for clinicians to determine which patients may require additional support during treatment. The purpose of this study was to determine if pretreatment myosteatosis is associated with a poor QOL trajectory following treatment completion.

METHODS: In a retrospective cohort design, myosteatosis was determined from pretreatment CT scans. Both physical and global QOL score was assessed through patient interview on follow-up appointment. Demographic, cancer-specific, and social covariates …

Development Of Personas To Communicate Narrative-Based Information About The Hpv Vaccine On Twitter, Philip M Massey, Shawn C Chiang, Meredith Rose, Regan M Murray, Madeline Rockett, Elikem Togo, Ann C Klassen, Jennifer A Manganello, Amy Leader

Department of Medical Oncology Faculty Papers

Introduction: Personas are based on real-life typologies of people that can be used to create characters and messages to communicate important health information through relatable narrative storylines. Persona development is data-driven and can involve multiple phases of formative research and evaluation; however, personas are largely underutilized in digital health research. The purpose of this study was to create and document persona development to deliver narrative-focused health education for parents on Twitter with the goal of increasing uptake of HPV vaccination among adolescents. Methods: Leveraging data from a mixed-method study conducted in the U.S. with a diverse population of parents with …

Simultaneous Ck2/Tnik/Dyrk1 Inhibition By 108600 Suppresses Triple Negative Breast Cancer Stem Cells And Chemotherapy-Resistant Disease., Katsutoshi Sato, Amol A. Padgaonkar, Stacey J. Baker, Stephen C. Cosenza, Olga Rechkoblit, D.R.C. Venkata Subbaiah, Josep Domingo-Domenech, Alison Bartkowski, Elisa R. Port, Aneel K. Aggarwal, M. V. Ramana Reddy, Hanna Y. Irie, E. Premkumar Reddy

Department of Medical Oncology Faculty Papers

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest …

Standardizing Definitions Of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, And Donor Chimerism In Allogeneic Hematopoietic Cell Transplantation: A Report On Behalf Of The American Society For Transplantation And Cellular Therapy., Mohamed A. Kharfan-Dabaja, Ambuj Kumar, Ernesto Ayala, Mahmoud Aljurf, Taiga Nishihori, Rebecca Marsh, Lauri M. Burroughs, Navneet Majhail, A. Samer Al-Homsi, Zaid S. Al-Kadhimi, Merav Bar, Alice Bertaina, Jaap J. Boelens, Richard Champlin, Sonali Chaudhury, Zachariah Defilipp, Bhagirathbhai Dholaria, Areej El-Jawahri, Suzanne Fanning, Ellen Fraint, Usama Gergis, Sergio Giralt, Betty K. Hamilton, Shahrukh K. Hashmi, Biljana Horn, Yoshihiro Inamoto, David A. Jacobsohn, Tania Jain, Laura Johnston, Abraham S. Kanate, Ankit Kansagra, Adetola Kassim, Leslie S. Kean, Carrie L. Kitko, Jessica Knight-Perry, Joanne Kurtzberg, Hien Liu, Margaret L. Macmillan, Zahra Mahmoudjafari, Marco Mielcarek, Mohamad Mohty, Arnon Nagler, Eneida Nemecek, Timothy S. Olson, Betul Oran, Miguel-Angel Perales, Susan E. Prockop, Michael A. Pulsipher, Iskra Pusic, Marcie L. Riches, Cesar Rodriguez, Rizwan Romee, Gabriela Rondon, Ayman Saad, Nina Shah, Peter J. Shaw, Shalini Shenoy, Jorge Sierra, Julie Talano, Michael R. Verneris, Paul Veys, John E. Wagner, Bipin N. Savani, Mehdi Hamadani, Paul A. Carpenter

Department of Medical Oncology Faculty Papers

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and …

Phase 1 Study Of Safety, Tolerability And Immunogenicity Of The Human Telomerase (Htert)-Encoded Dna Plasmids Ino-1400 And Ino-1401 With Or Without Il-12 Dna Plasmid Ino-9012 In Adult Patients With Solid Tumors, Robert H Vonderheide, Kimberly A Kraynyak, Anthony F Shields, Autumn J Mcree, Jennifer Johnson, Weijing Sun, Ashish V Chintakuntlawar, Jan Pawlicki, Albert J Sylvester, Trevor Mcmullan, Robert Samuels, Joseph J Kim, David Weiner, Jean D Boyer, Matthew P Morrow, Laurent Humeau, Jeffrey M Skolnik

Department of Medical Oncology Faculty Papers

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is frequently classified as a 'universal' tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.

METHODS: A phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse. Plasmid DNA encoding one of two hTERT variants (INO-1400 or INO-1401) with or without plasmid DNA encoding interleukin 12 (IL-12) (INO-9012) was delivered intramuscularly concurrent with the application of the CELLECTRA constant-current electroporation device …

Longitudinal Dynamics Of Circulating Tumor Cells And Circulating Tumor Dna For Treatment Monitoring In Metastatic Breast Cancer, Lorenzo Gerratana, Andrew A Davis, Qiang Zhang, Debora Basile, Giovanna Rossi, Kimberly Strickland, Alessandra Franzoni, Lorenzo Allegri, Zhaomei Mu, Youbin Zhang, Lisa E Flaum, Giuseppe Damante, William John Gradishar, Leonidas C Platanias, Amir Behdad, Hushan Yang, Fabio Puglisi, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

Liquid biopsy-based biomarkers, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). The aim of the study was to explore CTCs and ctDNA dynamics to better understand their potentially complementary role in describing MBC.

METHODS: The study retrospectively analyzed 107 patients with MBC characterized with paired CTCs and ctDNA assessments and a second prospective cohort, which enrolled 48 patients with MBC. CTCs were immunomagnetically isolated and ctDNA was quantified and then characterized through next-generation sequencing in the retrospective cohort and droplet digital polymerase chain reaction in the prospective …

Treating Early-Stage Dlbcl On The Flyer: What Lesson For Radiation Therapy?, Kelsey Sokol, Amanda Mcbride, Adam Binder, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

No abstract provided.

Integration Of Circulating Tumor Cell And Neutrophil-Lymphocyte Ratio To Identify High-Risk Metastatic Castration-Resistant Prostate Cancer Patients., Weelic Chong, Zhenchao Zhang, Rui Luo, Jian Gu, Jianqing Lin, Qiang Wei, Bingshan Li, Ronald E. Myers, Phd, Dsw, Grace Lu-Yao, William Kevin Kelly, Chun Wang, Hushan Yang

Department of Medical Oncology Faculty Papers

BACKGROUND: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs.

METHODS: Baseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models.

RESULTS: …

Whole-Exome Sequencing Identifies Somatic Mutations And Intratumor Heterogeneity In Inflammatory Breast Cancer., Rui Luo, Weelic Chong, Qiang Wei, Zhenchao Zhang, Chun Wang, Zhong Ye, Maysa Abu-Khalaf, Daniel P. Silver, Robert T. Stapp, Wei Jiang, Ronald E. Myers, Bingshan Li, Massimo Cristofanilli, Hushan Yang

Department of Medical Oncology Faculty Papers

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, …

Preparing Historically Underrepresented Trainees For Biomedical Cancer Research Careers At Huntsman Cancer Institute/University Of Utah Health., Ana Maria Lopez, Md, Mph, Macp, José E Rodríguez, Kathryn Browning Hawes, Anna Marsden, Don Ayer, Donna Harp Ziegenfuss, Kola Okuyemi

Department of Medical Oncology Faculty Papers

Given the well-documented inequities in health care outcomes by race, ethnicity, and gender, many health career pipeline programs have focused on supporting the development of a diverse and inclusive workforce. The State of Utah, is vast, but sparsely populated outside the Salt Lake City metropolitan area. More than 96% of our nearly 85,000 square miles is designated rural (<100 people/square mile) or frontier (<7 people/square mile). The Salt Lake City area is home to the Hunsman Cancer Institute, the only NCI-designated Comprehensive Cancer Center in the region, also noted the limited diversity in the biomedical cancer research workforce. Our primary objective was to increase the number of underrepresented trainees who pursue higher education with the goal of a career in cancer research. PathMaker is a regional, competitive pipeline program that nurtures high school or undergraduate trainees from historically underrepresented backgrounds towards a career in cancer research. Our faculty and staff team collaboratively developed a cohort model curriculum that increased student awareness of research …

A Phase I Trial Of The Met/Alk/Ros1 Inhibitor Crizotinib Combined With The Vegf Inhibitor Pazopanib In Patients With Advanced Solid Malignancies, Sarina A Piha-Paul, Ecaterina E Dumbrava, Binoj C Nair, Wendy Xiong, Li Xu, Rosa Mostorino, Vivek Subbiah, Nizar Tannir, Siqing Fu, Aung Naing, Filip Janku, Daniel D Karp, Shreyaskumar Patel, Najat C Daw, David Hong, Funda Meric-Bernstam, Ralph G. Zinner

Department of Medical Oncology Faculty Papers

Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue. The anti-angiogenic properties of pazopanib could overcome crizotinib drug resistance. Additionally, the anti-angiogenic properties of crizotinib could augment the clinical efficacy of pazopanib.

Methods: We evaluated the safety and responses in patients with advanced solid tumors treated with crizotinib and pazopanib.

Results: Eighty-two patients (median age 53 years, range 18-78 years) were enrolled. The median number of prior systemic therapies was 3 (range, 0-8). We were able to dose escalate to dose level 8 (crizotinib 250 mg twice daily and pazopanib …