Digital Commons Network^™

Icos And Icos Ligand: Expression Patterns And Outcomes In Oncology Patients, Mina Nikanjam, Shumei Kato, Daisuke Nishizaki, Donald A Barkauskas, Sarabjot Pabla, Jeffrey M Conroy, Razelle Kurzrock

Faculty, Staff and Student Publications

Background: Inducible T-cell co-stimulator (ICOS) and its ligand (ICOSL) form a complex, two-faced immune machinery that can lead to both immune stimulation and inhibition.

Objective: We explored ICOS transcriptomic expression patterns and their relationship with other checkpoints and with outcomes in patients with advanced/metastatic cancers.

Design: This was a retrospective cohort study.

Methods: RNA expression for ICOS and other immune checkpoints was quantified by RNA sequencing and stratified by rank values into high (75-100 percentiles) and low (0-24 percentiles). Fischer's exact tests were used for univariate analyses to evaluate independent predictors of ICOS high and logistic regression was used for …

Dose Planning And Radiation Optimization For Thoracic Conventional, Twice Daily, And Stereotactic Radiation Therapy: A Delphi Consensus From A National Survey Of Practitioners, Julius Weng, Jeff Ryckman, Matthew S Katz, Hina Saeed, Christopher Estes, Amy Moreno

Faculty, Staff and Student Publications

Purpose: We sent surveys to a large number of radiation oncologists with active thoracic cancer practices and applied the Delphi method over 3 rounds to generate consensus dose-volume histogram metrics. We used these results to create consensus-based organs-at-risk dose constraints and target goal templates for practical implementation.

Methods and materials: In this institutional review board-approved study, data were collected using REDCap electronic data capture on a secure server. Radiation oncologists identified from the Accreditation Council for Graduate Medical Education-accredited departments' websites were asked to confirm their self-identification as thoracic radiation oncologists and nominate other respondents. All invitees were asked to …

Longitudinal Genomic Profiling Of Chemotherapy-Related Chip Variants In Patients With Ovarian Cancer, Sara Corvigno, Jun Yao, Amma Asare, Li Zhao, Joseph Celestino, Ency A Arboleda Goette, Raymond N Montoya, Ping Song, Qingxiu C Zhang, Xingzhi Song, Mohammad M Mohammad, Kenna R Shaw, Jianhua Zhang, Karen H Lu, Amir A Jazaeri, Shannon N Westin, Anil K Sood, Sanghoon Lee

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis (CH) is characterized by the presence of hematopoietic stem cells (HSCs) with the potential of clonally expanding and giving rise to hematological malignancies. Clonal hematopoiesis of indeterminate potential (CHIP) is the outgrowth of a single HSC clone with an acquired somatic mutation in the absence of hematological abnormalities. CHIP variants occur with a variant allele frequency (VAF) of at least 2% in peripheral blood. This definition does not account for less frequent mutations that give rise to hematopoietic clones. Previous studies indicate an association between CH and secondary hematologic malignancies in cancer patients who receive chemotherapy.

Methods: …

Digital Twins In Healthcare: A Comprehensive Review And Future Directions, Hamid Khoshfekr Rudsari, Becky Tseng, Hongxu Zhu, Lulu Song, Chunhui Gu, Ehsan Irajizad, James Long, Kim-Anh Do

Faculty, Staff and Student Publications

Digital Twin (DT) technology has emerged as a transformative force in healthcare, offering unprecedented opportunities for personalized medicine, treatment optimization, and disease prevention. This comprehensive review examines the current state of DTs in healthcare, analyzing their implementation across different physiological levels-from cellular to whole-body systems. We systematically review the latest developments, methodologies, and applications while identifying challenges and opportunities. Our analysis encompasses technical frameworks for cardiovascular, neurological, respiratory, metabolic, hepatic, oncological, and cellular DTs, highlighting significant achievements such as population-scale cardiac modeling (3,461 patient cohort), reduced atrial fibrillation recurrence rates through patient-specific cardiac models, improved brain tumor radiotherapy planning, advanced …

Upregulation Of Delta Opioid Receptor By Meningeal Interleukin-10 Prevents Relapsing Pain, Kufreobong E Inyang, Jaewon Sim, Kimberly B Clark, Matan Geron, Karli Monahan, Patrick O'Connell, Bo Peng, Jiacheng Ma, Cobi J Heijnen, Robert Dantzer, Grégory Scherrer, Annemieke Kavelaars, Matthew Bernard, Yasser A Aldhamen, Joseph K Folger, Alexis Bavencoffe, Geoffroy Laumet

Faculty, Staff and Student Publications

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological …

Effect Of Digital Health Coaching On Self-Efficacy And Patient-Reported Outcomes In Individuals With Acute Myeloid And Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial, Jennifer Marvin-Peek, Valerie Shelton, Kelly Brassil, Bryan Fellman, Austin Barr, Danielle Hammond, Nitin Jain, William Wierda, Alessandra Ferrajoli, Courtney Dinardo

Faculty, Staff and Student Publications

Introduction: Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.

Methods: Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.

Results: A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December …

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nicole Hensch, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

Safety And Activity Of Ctx130, A Cd70-Targeted Allogeneic Crispr-Cas9-Engineered Car T-Cell Therapy, In Patients With Relapsed Or Refractory T-Cell Malignancies (Cobalt-Lym): A Single-Arm, Open-Label, Phase 1, Dose-Escalation Study, Swaminathan P Iyer, R Alejandro Sica, P Joy Ho, Anca Prica, Jasmine Zain, Boyu Hu, Wen-Kai Weng, Youn H Kim, Michael S Khodadoust, Auris O Huen, Leah M Williams, Anna Ma, Elaine Huang, Avanti Ganpule, Shashwat Deepali Nagar, Parin Sripakdeevong, Erika L Cullingford, Sushant Karnik, Mary-Lee Dequeant, Janki N Patel, Xinyi Shirley He, Ziliang Li, Qiuling Ally He, Joy H Mendonez, Alissa Keegan, Steven M Horwitz

Faculty, Staff and Student Publications

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative …

Impact Of Active Surveillance On Nephrometric Scores Of Bosniak Iii And Iv Renal Cysts, Roberto Dias Machado, Leonardo Bernardes De Amaro, Alessandro Prudente, Eliney Ferreira Faria, Antonio Antunes Rodrigues Júnior, Jose A Karam, Leonardo O Reis, Rodolfo Borges Dos Reis

Faculty, Staff and Student Publications

Purpose: Active surveillance (AS) has been widely explored for small renal masses, but its role in complex renal cysts (CRCs) categorized as Bosniak (Bk) III and IV remains unclear. This study aims to evaluate changes in nephrometry scores (s-RENAL and s-PADUA) during AS and their potential impact on surgical complexity.

Methods: A retrospective, multicentric, observational study was conducted, analyzing 101 CRCs from 95 patients across three institutions. Nephrometry scores were evaluated at baseline and after a minimum follow-up of two years using computed tomography (CT) and magnetic resonance imaging (MRI). Statistical analysis included chi-square and marginal homogeneity tests, with data …

Optimal Timing Of Organs-At-Risk-Sparing Adaptive Radiation Therapy For Head-And-Neck Cancer Under Re-Planning Resource Constraints, Fatemeh Nosrat, Cem Dede, Lucas B Mccullum, Raul Garcia, Abdallah S R Mohamed, James E Bates, Kareem A Wahid, Mohamed A Naser, Renjie He, Aysenur Karagoz, Amy C Moreno, Lisanne V Van Dijk, Kristy K Brock, Jolien Heukelom, Seyedmohammadhossein Hosseinian, Mehdi Hemmati, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Background and purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing of re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC).

Materials and methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for …

Novel Volumetric Modulated Arc Therapy Approach For Lattice Radiation Therapy For Bulky Liver Tumors, Christine V Chung, Saurabh S Nair, Meena S Khan, Callistus I Nguyen, Rachael M Martin-Paulpeter, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Lattice radiation therapy (LRT) is a type of spatially fractionated radiation therapy that has emerged as an effective treatment approach for bulky solid tumors. RapidArc Dynamic (RAD) is a novel beam delivery approach that may be advantageous for LRT. The purpose of this in silico study was to evaluate and compare a novel RAD-based LRT approach (RAD-LRT) with conventional volumetric modulated arc therapy (VMAT)-based LRT (VMAT-LRT).

Methods: Twenty patients with bulky liver tumors treated with RT were retrospectively identified. VMAT-LRT and RAD-LRT plans were generated for all patients. Lattice spheres were placed in a standardized hexagonal pattern with alternating …

Defining Spine Cancer Pain Syndromes: A Systematic Review And Proposed Terminology, Markian Pahuta, Ilya Laufer, Sheng-Fu Larry Lo, Stefano Boriani, Charles Fisher, Michael H Weber, Arjun Sahgal, Laurence Rhines, Jeremy Reynolds, Aron Lazary, Alessandro Gasbarrinni, Jorrit-Jan Verlaan, Ziya Gokaslan, Chetan Bettegowda, Mohamed Sarraj, Ori Barzilai, Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

STUDY DESIGN: Systematic Review.

OBJECTIVES: Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients.

METHODS: We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists.

RESULTS: Our literature search identified 3515 unique citations. Through …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

Erratum: Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification: Erratum, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Fufu Zheng, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

No abstract provided.

Erratum: Long Non-Coding Rna Uiclm Promotes Colorectal Cancer Liver Metastasis By Acting As A Cerna For Microrna-215 To Regulate Zeb2 Expression: Erratum, Dong-Liang Chen, Yun-Xin Lu, Jia-Xing Zhang, Xiao-Li Wei, Feng Wang, Zhi-Zhong Pan, Feng-Hua Wang, Helene Pelicano, Paul J Chiao, Peng Huang, Dan Xie, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

No abstract provided.

Ganglioside Gd2 Contributes To A Stem-Like Phenotype In Intrahepatic Cholangiocarcinoma, Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Benedetta Piombanti, Elisabetta Rovida, Cédric Coulouarn, Jesper B Andersen, Monika Lewinska, Claudia Campani, V Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Faculty, Staff and Student Publications

BACKGROUND & AIMS: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

METHODS: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The …

Development Of Microcystoid Macular Degeneration In The Retina Of Nonhuman Primates: Time-Course And Associated Pathologies, Thomas C M Lavery, Carol A Rasmussen, Alexander W Katz, Charlene B Y Kim, James N Ver Hoeve, Peter J Sonnentag, Christopher J Murphy, David R Piwnica-Worms, Seth T Gammon, Xudong Qiu, Paul L Kaufman, T Michael Nork

Faculty, Staff and Student Publications

Purpose: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.

Methods: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous …

A Pan-Tumor Review Of The Role Of Poly(Adenosine Diphosphate Ribose) Polymerase Inhibitors, Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh, Zeynep Irem Ozay, Arshit Narang, Talia Golan, Umang Swami, Kathleen N Moore, Neeraj Agarwal

Faculty, Staff and Student Publications

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical …

Racial Differences In Systemic Immune Parameters In Individuals With Lung Cancer, Mitchell S Von Itzstein, Jialiang Liu, Hong Mu-Mosley, Farjana Fattah, Jason Y Park, J David Farrar, David Hsiehchen, Yvonne Gloria-Mccutchen, Edward K Wakeland, Suzanne Cole, Sheena Bhalla, Radhika Kainthla, Igor Puzanov, Benjamin Switzer, Gregory A Daniels, Yousef Zakharia, Montaser Shaheen, Jianjun Zhang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Introduction: Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer.

Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pretreatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons.

Results: A …

Distribution Of Chronic Wasting Disease (Cwd) Prions In Tissues From Experimentally Exposed Coyotes (Canis Latrans), Nancy Ho, Reece Mcginn, Paulina Soto, Terry R Spraker, Justin Fischer, Tracy Nichols

Faculty, Staff and Student Publications

Cervids susceptible to chronic wasting disease (CWD) are sympatric with multiple other animal species that can interact with infectious prions. Several reports have described the susceptibility of other species to CWD prions, or their potential to transport them. One of these species is the coyote (Canis latrans), which has been previously shown to pass transmission-relevant prion titers in their feces for at least three days after ingesting prion-positive brain material. The current study followed up on these findings and evaluated the distribution of prions in multiple tissues from the same coyotes. Our results show that prions persist in the digestive …

Home Dialysis For Latinx Individuals Living With Kidney Failure: A Qualitative Study Of Interdisciplinary Dialysis Clinicians, Sushrut S Waikar

Faculty, Staff and Student Publications

Key Points:

1. Individual-level advocacy to overcome structural barriers to home dialysis is key in improving home dialysis access for Latinx individuals.

2. Acknowledging patient influences on dialysis modality choice is critical for Latinx individuals with kidney failure.

3. Early, repeated education from a trusted source is important for Latinx individuals with kidney failure.

Background: Latinx individuals experience two times the incidence of kidney failure compared with non-Latinx individuals and are less likely to use home dialysis therapies. In this qualitative study, interdisciplinary home dialysis clinicians were interviewed to understand the key factors and strategies used by clinicians to improve home dialysis uptake …

The Association Between Food Benefit Online Ordering And Redemptions: Evidence From The Special Supplemental Nutrition Program For Women, Infants, And Children, Junzhou Zhang, Chuanyi Tang, Kayoung Park, Qi Zhang

Marketing Faculty Publications

Objective:

To examine how the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) online food benefit ordering could influence WIC benefit redemptions.

Design:

A cross-sectional study. We compare the average redemption rates between online ordering early adopters and non-adopters among WIC customers before and after implementing WIC online ordering. A propensity score-weighted difference-in-difference model was used to estimate the coefficients.

Setting:

The Oklahoma WIC programme and a grocery store chain in Oklahoma.

Participants:

12743 Oklahoma WIC households that had redeemed their food benefits at the grocery store chain in 2020.

Results:

WIC online ordering significantly positively affected redemption …

(In)Attention To Attractive Brand Alternatives, Danielle J. Brick, Veronica L. Thomas

Marketing Faculty Publications

Understanding how consumers maintain their brand relationships has important implications for marketers as committed consumers contribute significant value to firms. In the present research, we propose and test one such way consumers protect their brand relationships, namely through attentional avoidance of attractive alternative partners. Across multiple studies, we find support for our theory that committed consumers avoid attending to alternative brand partners by recalling less about and spending less time focused on attractive alternatives. We further find that this inattention occurs because consumers view the competing brand as a threat to the consumer’s current relationship. In addition, we investigate a …