Medicine and Health Sciences Commons^™

Gpu Accelerated Estimation Of A Shared Random Effect Joint Model For Dynamic Prediction, Shikun Wang, Zhao Li, Lan Lan, Jieyi Zhao, W Jim Zheng, Liang Li

Faculty, Staff and Student Publications

In longitudinal cohort studies, it is often of interest to predict the risk of a terminal clinical event using longitudinal predictor data among subjects at risk by the time of the prediction. The at-risk population changes over time; so does the association between predictors and the outcome, as well as the accumulating longitudinal predictor history. The dynamic nature of this prediction problem has received increasing interest in the literature, but computation often poses a challenge. The widely used joint model of longitudinal and survival data often comes with intensive computation and excessive model fitting time, due to numerical optimization and …

Reducing Time To Antibiotics In Patients With Neutropenic Fever On A Bone Marrow Transplant Unit, Regina Mcguire, Christopher Anand Gardner, Jordan Villars, William O'Hara, Jessica Radicke, Felicia Rivera, Jill Cristiano, Joanne E. Filicko-O'Hara, Usama Gergis, Adam F. Binder

Student Papers, Posters & Projects

Background/Methods: Timely administration of antibiotics in patients with neutropenic fever (NF) is essential for reducing morbidity and mortality among oncology patients. The optimal time to antibiotics (TTA) for patients with NF is unclear, but IDSA/ASCO guidelines recommend a median TTA within one hour of documented fever. This study focused on identifying barriers at a single academic institution to timely antibiotic administration for patients admitted to the inpatient Bone Marrow Transplant (BMT) unit, and implemented new processes to reduce median TTA to less than 60 minutes.

Methods: Chart reviews were performed to identify causes for delays in antibiotics (abx). Based on …

Association Of Pd-L1 Expression And Other Variables With Benefit From Immune Checkpoint Inhibition In Advanced Gastroesophageal Cancer: Systematic Review And Meta-Analysis Of 17 Phase 3 Randomized Clinical Trials, Harry H Yoon, Zhaohui Jin, Oudom Kour, Lionel Aurelien Kankeu Fonkoua, Kohei Shitara, Michael K Gibson, Larry J Prokop, Markus Moehler, Yoon-Koo Kang, Qian Shi, Jaffer A Ajani

Faculty, Staff and Student Publications

Importance: Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.

Objective: To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.

Data sources: MEDLINE, Embase, Scopus, Web of Science, Cochrane …

Residence In A Latinx Enclave And End-Induction Minimal Residual Disease Positivity Among Children With Acute Lymphoblastic Leukemia, Joshua P Muñiz, John P Woodhouse, Amy E Hughes, Sandi L Pruitt, Karen R Rabin, Michael E Scheurer, Philip J Lupo, Jeremy M Schraw

Center for Medical Ethics and Health Policy Staff Publications

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase …

Incidence And 5-Year Survival Of Children And Adolescents With Hepatoblastoma In The United States, Justin A Kahla, David A Siegel, Shifan Dai, Philip J Lupo, Jennifer H Foster, Michael E Scheurer, Andras A Heczey

Center for Medical Ethics and Health Policy Staff Publications

Objective: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized.

Methods: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression …

Systematically Higher Ki67 Scores On Core Biopsy Samples Compared To Corresponding Resection Specimen In Breast Cancer: A Multi-Operator And Multi-Institutional Study, Balazs Acs, Samuel C Y Leung, Kelley M Kidwell, Indu Arun, Renaldas Augulis, Sunil S Badve, Yalai Bai, Anita L Bane, John M S Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C Chang, Robin L Dietz, Andrew Dodson, Susan Fineberg, Cornelia M Focke, Dongxia Gao, Allen M Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Lænkholm, Arvydas Laurinavicius, Richard M Levenson, Rustin Mahboubi-Ardakani, Mauro G Mastropasqua, Sharon Nofech-Mozes, C Kent Osborne, Frédérique M Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert Van Der Vegt, Giuseppe Viale, Lila A Zabaglo, Daniel F Hayes, Mitch Dowsett, Torsten O Nielsen, David L Rimm, International Ki67 In Breast Cancer Working Group Of The Breast International Group And North American Breast Cancer Group (Big-Nabcg)

Faculty, Staff and Students Publications

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut …

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 …

Lymph Node Dissections And Survival In Sublobar Resection Of Non-Small Cell Lung Cancer ≤ 20 Mm., Shinkichi Takamori, Takefumi Komiya Md, Mototsugu Shimokawa, Emily Powell Phd

PCI Publications and Projects

BACKGROUND: A randomized trial of lobectomy versus segmentectomy for small-sized (≤ 20 mm) non-small cell lung cancer (NSCLC) showed that patients who had undergone segmentectomy had a significantly longer overall survival (OS) than those who had lobectomy. More attention is needed regarding the required extent of thoracic lymphadenectomy in patients with small-sized NSCLC who undergo sublobar resection.

METHODS: The National Cancer Database was queried for patients with clinically node-negative NSCLC ≤ 20 mm who had undergone sublobar resection between 2004 and 2017. OS of NSCLC patients by the number of lymph node dissections (LNDs) was analyzed using log-rank tests and …

Characteristics Of Community-Acquired Carbapenem-Resistant Enterobacterales, Rima Shrestha, Courtney L Luterbach, Weixiao Dai, Lauren Komarow, Michelle Earley, Gregory Weston, Erica Herc, Jesse T Jacob, Robert Salata, Darren Wong, Deverick Anderson, Kirsten B Rydell, Cesar A Arias, Liang Chen, David Van Duin, Mdro Investigators

Faculty, Staff and Student Publications

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.

METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.

RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was …

Pin-Pointing The Key Hubs In The Ifn-Γ Pathway Responding To Sars-Cov-2 Infection, Ayelen Toro, Sofia Lage-Vickers, Juan Bizzotto, Felipe Vilicich, Agustina Sabater, Gaston Pascual, Sabrina Ledesma-Bazan, Pablo Sanchis, Maria Sol Ruiz, Ana Paula Arevalo, Jorge L Porfido, Mercedes Abbate, Rocio Seniuk, Estefania Labanca, Nicolas Anselmino, Nora M Navone, Daniel F Alonso, Elba Vazquez, Martina Crispo, Javier Cotignola, Geraldine Gueron

Faculty, Staff and Student Publications

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) …

Early Versus Late Discontinuation Of Maintenance Therapy In Multiple Myeloma., Jordan Nunnelee, Francesca Cottini, Qiuhong Zhao, Muhammad Salman Faisal, Patrick Elder, Ashley Rosko, Naresh Bumma, Abdullah Khan, Elvira Umyarova, Srinivas Devarakonda, Don M Benson, Yvonne A Efebera, Nidhi Sharma

Oncology Articles

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) …

Prognostic Molecular Biomarkers In Chordomas: A Systematic Review And Identification Of Clinically Usable Biomarker Panels, Franco Rubino, Christopher Alvarez-Breckenridge, Kadir Akdemir, Anthony P Conley, Andrew J Bishop, Wei-Lien Wang, Alexander J Lazar, Laurence D Rhines, Franco Demonte, Shaan M Raza

Faculty, Staff and Student Publications

INTRODUCTION AND OBJECTIVE: Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis.

METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) …

Exercise Counselling And Referral In Cancer Care: An International Scoping Survey Of Health Care Practitioners’ Knowledge, Practices, Barriers, And Facilitators, Imogen Ramsey, Alexandre Chan, Andreas Charalambous, Yin Ting Cheung, H. S. Darling, Lawson Eng, Lisa Grech, Nicolas H. Hart, Deborah Kirk, Sandra A. Mitchell, Dagmara Poprawski, Elke Rammant, Margaret I. Fitch, Raymond J. Chan

Research outputs 2022 to 2026

Purpose:

Evidence supports the role of prescribed exercise for cancer survivors, yet few are advised to exercise by a healthcare practitioner (HCP). We sought to investigate the gap between HCPs’ knowledge and practice from an international perspective.

Methods:

An online questionnaire was administered to HCPs working in cancer care between February 2020 and February 2021. The questionnaire assessed knowledge, beliefs, and practices regarding exercise counselling and referral of cancer survivors to exercise programs.

Results:

The questionnaire was completed by 375 participants classified as medical practitioners (42 %), nurses (28 %), exercise specialists (14 %), and non-exercise allied health practitioners (16 …

Mucus-Degrading Bacteroides Link Carbapenems To Aggravated Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Mohamed A Jamal, Takahiko Miyama, Chia-Chi Chang, Miriam R Ortega, Saira S Ahmed, Jennifer L Karmouch, Christopher A Sanchez, Alexandria N Brown, Rawan K El-Himri, Ivonne I Flores, Lauren K Mcdaniel, Dung Pham, Taylor Halsey, Annette C Frenk, Valerie A Chapa, Brooke E Heckel, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J Ajami, Jennifer A Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F Chemaly, Lauren Davey, Robert W P Glowacki, Chen Liu, Gabriela Rondon, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Raphael H Valdivia, Eric C Martens, Philip L Lorenzi, Robert R Jenq

Faculty, Staff and Student Publications

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic …

Testing A Behavioral Activation Gaming App For Depression During Pregnancy: Multimethod Pilot Study, Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Stephanie T Juenger, Tommaso Sciortino, Francesco Bruno, Nico Teske, Ramin A Morshed, Alexander F Haddad, Yalan Zhang, Sophia Stoecklein, Michael A Vogelbaum, Juergen Beck, Nitin Tandon, Shawn Hervey-Jumper, Annette M Molinaro, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Martin Van Den Bent, Michael Weller, Mitchel S Berger, Susan M Chang, Joerg-Christian Tonn

Faculty, Staff and Student Publications

In IDH-wildtype glioblastomas which meet the histopathological or molecular diagnosis criteria, it remains unclear whether the presence of TERT promotor mutations provides additional prognostic information. Based on a multicenter cohort of 466 IDH-wildtype glioblastomas (including 396 with and 70 patients without TERT promotor mutations), we found that TERT promotor mutations were neither associated with progression-free survival nor overall survival. This held true in various treatment-based or molecular subgroups. This argues against standardized analysis for TERT promotor mutation status for the purpose of prognostic or therapeutic relevance in newly diagnosed IDH-wildtype glioblastoma that otherwise meets the histopathological and …

Impact Of Different Unconditional Monetary Incentives On Survey Response Rates In Men With Prostate Cancer: A 2-Arm Randomised Trial, Megan Mcintosh, Melissa J. Opozda, Michael O’Callaghan, Andrew D. Vincent, Daniel A. Galvão, Camille E. Short

Research outputs 2022 to 2026

Background:

Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of small monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case–control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-min questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded …

Diffusing Alpha-Emitters Radiation Therapy In Combination With Temozolomide Or Bevacizumab In Human Glioblastoma Multiforme Xenografts, Yossi Nishri, Maayan Vatarescu, Ishai Luz, Lior Epstein, Mirta Dumančić, Sara Del Mare, Amit Shai, Michael Schmidt, Lisa Deutsch, Robert Den, Itzhak Kelson, Yona Keisari, Lior Arazi, Tomer Cooks, Vered Domankevich

Department of Radiation Oncology Faculty Papers

Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ …

Molecular Pathways Enhance Drug Response Prediction Using Transfer Learning From Cell Lines To Tumors And Patient-Derived Xenografts, Yi-Ching Tang, Reid T Powell, Assaf Gottlieb

Faculty, Staff and Student Publications

Computational models have been successful in predicting drug sensitivity in cancer cell line data, creating an opportunity to guide precision medicine. However, translating these models to tumors remains challenging. We propose a new transfer learning workflow that transfers drug sensitivity predicting models from large-scale cancer cell lines to both tumors and patient derived xenografts based on molecular pathways derived from genomic features. We further compute feature importance to identify pathways most important to drug response prediction. We obtained good performance on tumors (AUROC = 0.77) and patient derived xenografts from triple negative breast cancers (RMSE = 0.11). Using feature importance, …

A Facile Synthetic Method For Anhydride From Carboxylic Acid With The Promotion Of Triphenylphosphine Oxide And Oxaloyl Chloride, Mengyu Lu, Huihui Fan, Qing Liu, Xiaoling Sun

Faculty, Staff and Student Publications

A highly efficient synthesis reaction of carboxylic anhydrides catalyzed by triphenylphosphine oxide is described for the quick synthesis of a range of symmetric carboxylic anhydrides and cyclic anhydrides under mild and neutral conditions with a high yield. The system adopts the strong reactive intermediate Ph3PCl2 as the catalyst of carboxylic acid salt; driven by catalytic reaction, the synthesis takes a relatively short time to complete.

Impad1 And Syt11 Work In An Epistatic Pathway That Regulates Emt-Mediated Vesicular Trafficking To Drive Lung Cancer Invasion And Metastasis, Rakhee Bajaj, B Leticia Rodriguez, William K Russell, Amanda N Warner, Lixia Diao, Jing Wang, Maria G Raso, Wei Lu, Khaja Khan, Luisa S Solis, Harsh Batra, Ximing Tang, Jared F Fradette, Samrat T Kundu, Don L Gibbons

Faculty, Staff and Student Publications

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput in vitro and in vivo screens, we have previously established Impad1 as a driver of lung cancer invasion and metastasis. Here we elucidate that Impad1 is a direct target of the epithelial microRNAs (miRNAs) miR-200 and miR∼96 and is de-repressed during epithelial-to-mesenchymal transition (EMT); thus, we establish a mode of regulation of the protein. Impad1 modulates Golgi apparatus morphology and vesicular trafficking through its interaction with a trafficking protein, Syt11. These changes in Golgi apparatus dynamics alter …

The Co-Expression Of Ror1 And Fzd2 In Wnt5b Signaling In Osteosarcoma, Alec J. Wright, Susan Miranda Phd, Gustavo Miranda-Carboni Phd

Longitudinal Scholar's Project

Osteosarcoma is the most common primary bone malignancy. There is currently no targeted therapy, so standard treatment involves surgical resection along with chemotherapy. There is a large subset of osteosarcoma that has a high expression of WNT5B, which is linked to a worse overall survival probability. The WNT5B pathway in osteosarcoma is not known, so we wanted to find out what receptors it signals through. We came up with two candidates, ROR1 and FZD2, then tested our hypothesis using immunohistochemistry. We first optimized the antigen retrieval step and ROR1 primary antibody for our immunohistochemistry protocol then proceeded to test our …

Diagnostic Accuracy Of Ultrasound In Predicting Extrathyroidal Extension And Its Relation To Body Mass Index In A North American Population, Mahmoud Omar, Abdallah S. Attia, Peter P. Issa, Bryce R. Christensen, Kavin Sugumar, Ahmed Alnahla, Deena Hadedeya, Hosam Shalaby, Neel Gupta, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Detection of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) influences treatment plan and surgical aggressiveness. Ultrasound (US) is the long-standing preoperative imaging method of choice. Recent literature from Asia suggests US accuracy to be influenced by patient characteristics, such as body mass index (BMI). Here, we examine the effect of BMI on the accuracy of US at a North American tertiary referral center. A total of 204 PTC-confirmed patients were retrospectively read by a radiologist blinded to surgical pathology findings. The radiologist recorded multiple sonographic features, including ETE, loss of echogenic capsule, nodule vascularity, capsular abutment, and …

Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Yixin Yao, Lei Nie, Yang Liu, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.

METHODS: To interrogate BA resistance mechanisms in MCL, we …

Cancer As A Channelopathy—Appreciation Of Complimentary Pathways Provides A Different Perspective For Developing Treatments, Harry J. [email protected] Gould, Dennis Paul

School of Medicine Faculty Publications

Life depends upon the ability of cells to evaluate and adapt to a constantly changing environment and to maintain internal stability to allow essential biochemical reactions to occur. Ions and ion channels play a crucial role in this process and are essential for survival. Alterations in the expression of the transmembrane proteins responsible for maintaining ion balance that occur as a result of mutations in the genetic code or in response to iatrogenically induced changes in the extracellular environment is a characteristic feature of oncogenesis and identifies cancer as one of a constellation of diseases known as channelopathies. The classification …

To Bind Or Not To Bind: Cistromic Reprogramming In Prostate Cancer, Michelle Shen, Léa-Kristine Demers, Swneke D Bailey, David P Labbé

Faculty, Staff and Student Publications

The term "cistrome" refers to the genome-wide location of regulatory elements associated with transcription factor binding-sites. The cistrome of key regulatory factors in prostate cancer etiology are substantially reprogrammed and altered during prostatic transformation and disease progression. For instance, the cistrome of the androgen receptor (AR), a ligand-inducible transcription factor central in normal prostate epithelium biology, is directly impacted and substantially reprogrammed during malignant transformation. Accumulating evidence demonstrates that additional transcription factors that are frequently mutated, or aberrantly expressed in prostate cancer, such as the pioneer transcription factors Forkhead Box A1 (FOXA1), the homeobox protein HOXB13, and the GATA binding …

Smoking And Other Determinants Of Covid Severity Among Cancer Patients, Sameh Gomaa, Lindsay Wilde, Md, Tara Rakiewicz, Kuang-Yi Wen

Department of Medical Oncology Posters

Introduction

• Cancer patients might be more susceptible to COVID-19 infection.
• With a higher incidence of acute complications, severe disease and higher mortality rates.
• Identifying factors contributing to severe disease remains essential to avoid the risk of severe and often fatal COVID-19 exposure.
• We report on the predisposing factors for severe COVID-19 and increased hospitalization burden in cancer patients at the Sidney Kimmel Cancer Center (SKCC) in Philadelphia.

Determining Front-Line Therapeutic Strategy For Metastatic Clear Cell Renal Cell Carcinoma, Kevin K Zarrabi, Oladimeji Lanade, Daniel M Geynisman

Department of Medical Oncology Faculty Papers

The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development …

Therapeutic Management Of Chronic Lymphocytic Leukemia Presenting With Recurrent Massive Ascites, Ugochi Ebinama, Nathaniel R Wilson, Anindita Ghosh, Binsah S George

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient's ascitic fluid were consistent with CLL, and he …

Kshv (Hhv8) Vaccine: Promises And Potential Pitfalls For A New Anti-Cancer Vaccine, Corey Casper, Lawrence Corey, Jeffrey I. Cohen, Blossom Damania, Anne A. Gershon, David C. Kaslow, Laurie T. Krug, Jeffrey Martin, Sam M. Mbulaiteye, Edward S. Mocarski, Patrick S. Moore, Javier Gordon Ogembo, Warren Phipps, Denise Whitby, Charles Wood

School of Medicine Faculty Publications

Seven viruses cause at least 15% of the total cancer burden. Viral cancers have been described as the “low-hanging fruit” that can be potentially prevented or treated by new vaccines that would alter the course of global human cancer. Kaposi sarcoma herpesvirus (KSHV or HHV8) is the sole cause of Kaposi sarcoma, which primarily afflicts resource-poor and socially marginalized populations. This review summarizes a recent NIH-sponsored workshop’s findings on the epidemiology and biology of KSHV as an overlooked but potentially vaccine-preventable infection. The unique epidemiology of this virus provides opportunities to prevent its cancers if an effective, inexpensive, and well-tolerated …

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results Of A Phase Iii Trial, Anamaria R Yeung, Snehal Deshmukh, Ann H Klopp, Karen M Gil, Lari Wenzel, Shannon N Westin, Andre A Konski, David K Gaffney, William Small, J Spencer Thompson, Desiree E Doncals, Guilherme H C Cantuaria, David P D'Souza, Amy Chang, Vijayananda Kundapur, Dasarahally S Mohan, Michael L Haas, Yong Bae Kim, Catherine L Ferguson, Stephanie L Pugh, Lisa A Kachnic, Deborah W Bruner

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available.

Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation …