Biomedical Informatics Commons^™

Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Hagop M Kantarjian, Farhad Ravandi-Kashani, Carlos Bueso-Ramos, Rashmi Kanagal-Shamanna, Elias Jabbour, Guillermo Montalban-Bravo, Nicholas J Short, Naval Daver, Gautam Borthakur, Courtney D Dinardo, Tapan M Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki

Faculty, Staff and Student Publications

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics …

Low-Molecular Weight Cyclin E Confers A Vulnerability To Pkmyt1 Inhibition In Triple-Negative Breast Cancer, Mi Li, Amriti R Lulla, Yan Wang, Spyros Tsavaschidis, Fuchenchu Wang, Cansu Karakas, Tuyen D T Nguyen, Tuyen N Bui, Marc A Pina, Mei-Kuang Chen, Sofia Mastoraki, Asha S Multani, Natalie W Fowlkes, Aysegul Sahin, C Gary Marshall, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin E is a regulatory subunit of CDK2 that mediates S phase entry and progression. The cleavage of full-length cyclin E (FL-cycE) to low-molecular weight isoforms (LMW-E) dramatically alters substrate specificity, promoting G1-S cell cycle transition and accelerating mitotic exit. Approximately 70% of triple-negative breast cancers (TNBC) express LMW-E, which correlates with poor prognosis. PKMYT1 also plays an important role in mitosis by inhibiting CDK1 to block premature mitotic entry, suggesting it could be a therapeutic target in TNBC expressing LMW-E. In this study, analysis of tumor samples of patients with TNBC revealed that coexpression of LMW-E and PKMYT1-catalyzed CDK1 …

What Do Cancer Genetic Providers Want Us To Know About Variant Reclassification And Recontact That We Are Not Asking? A Thematic Analysis Of Open-Ended Survey Responses, Kerri Brown, Marisel Ponton, Elenita Davidson, Banu Arun, Robert J Volk, Sanjay Shete, Susan K Peterson, Sukh Makhnoon

Faculty, Staff and Student Publications

BACKGROUND: Accurate variant classification and relaying reclassified results to patients is critical for hereditary cancer care delivery. Over a 5- to 10-year period, 6%-15% of variants undergo reclassification. As the frequency of reclassifications increases, the issue of whether, how, when, and which providers should recontact patients becomes important but remains contentious.

METHODS: The authors used inductive thematic analysis to analyze open-ended comments offered by oncologists and genetic counselors (GCs) from a large national survey.

RESULTS: Of the 634 oncologists and cancer GCs, 126 (20%) offered substantive free-text comments. Four thematic areas emerged: 1) ambiguity over professional responsibility to recontact, 2) …

Personalized Composite Dosimetric Score-Based Machine Learning Model Of Severe Radiation-Induced Lymphopenia Among Patients With Esophageal Cancer, Yan Chu, Cong Zhu, Brian P Hobbs, Yiqing Chen, Peter S N Van Rossum, Clemens Grassberger, Degui Zhi, Steven H Lin, Radhe Mohan

Faculty, Staff and Student Publications

Purpose: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiation therapy (RT)' Severe RIL has been linked to adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dosimetric parameters, e.g. dose-volume (DV) indices, are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of "composite dosimetric score" (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 RIL …

Clonal Hematopoiesis And Solid Tumor Risk: New Insights From The Women's Health Initiative, Nehali Shah, Koichi Takahashi

Faculty, Staff and Student Publications

No abstract provided.

Oncolytic Virotherapies And Adjuvant Gut Microbiome Therapeutics To Enhance Efficacy Against Malignant Gliomas, Natalie M Meléndez-Vázquez, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most prevalent malignant brain tumor. Current standard-of-care treatments offer limited benefits for patient survival. Virotherapy is emerging as a novel strategy to use oncolytic viruses (OVs) for the treatment of GBM. These engineered and non-engineered viruses infect and lyse cancer cells, causing tumor destruction without harming healthy cells. Recent advances in genetic modifications to OVs have helped improve their targeting capabilities and introduce therapeutic genes, broadening the therapeutic window and minimizing potential side effects. The efficacy of oncolytic virotherapy can be enhanced by combining it with other treatments such as immunotherapy, chemotherapy, or radiation. Recent studies …

Evidence That Crispr-Cas9 Y537s-Mutant Expressing Breast Cancer Cells Activate Yes-Associated Protein 1 To Driving The Conversion Of Normal Fibroblasts Into Cancer-Associated Fibroblasts, Luca Gelsomino, Amanda Caruso, Emine Tasan, Adele Elisabetta Leonetti, Rocco Malivindi, Giuseppina Daniela Naimo, Francesca Giordano, Salvatore Panza, Guowei Gu, Benedetta Perrone, Cinzia Giordano, Loredana Mauro, Bruno Nardo, Gianfranco Filippelli, Daniela Bonofiglio, Ines Barone, Suzanne A W Fuqua, Stefania Catalano, Sebastiano Andò

Faculty, Staff and Students Publications

BACKGROUND: Endocrine therapy (ET) has improved the clinical outcomes of Estrogen receptor alpha-positive (ERɑ +) breast cancer (BC) patients, even though resistance to ET remains a clinical issue. Mutations in the hormone-binding domain of ERɑ represent an acquired intrinsic mechanism of ET resistance. However, the latter also depends on the multiple functional interactions between BC cells and the tumor microenvironment (TME). Here, we investigated how the most common Y537S-ERɑ mutation may influence the behavior of fibroblasts, the most prominent component of the TME.

METHODS: We conducted coculture experiments with normal human foreskin fibroblasts BJ1-hTERT (NFs), cancer-associated fibroblasts (CAFs), isolated from …

Ar (Cag)N Microsatellite And Apex1 C444t>G (Pasp148glu) Polymorphisms As Independent Prognostic Biomarkers In Prostate Cancer: Insights From An Argentinian Cohort, Gaston Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Sabrina Ledesma-Bazan, Estefania Labanca, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Federico Prada, Geraldine Gueron, Javier Cotignola

Faculty, Staff and Student Publications

Background/objectives: Prostate cancer (PCa) is the leading malignancy and the third most common cause of cancer-related death in Argentinian men. Predicting outcomes in localized PCa remains difficult due to tumor heterogeneity. In this study, we assessed the impact of AR (CAG)n and APEX1 c.444T>G polymorphisms on biochemical relapse in Argentine patients with localized PCa.

Methods: We genotyped blood samples from 123 PCa patients for AR (CAG)n and APEX1 p.Asp148Glu (c.444T>G) polymorphisms. Associations with clinicopathological parameters and biochemical relapse-free survival (BRFS) were assessed.

Results: AR (CAG)20-23 was associated with a family history of breast/ovarian cancer (p = 0.0469). …

The Il-1Β Inhibitor Canakinumab In Previously Treated Lower-Risk Myelodysplastic Syndromes: A Phase 2 Clinical Trial, Juan Jose Rodriguez-Sevilla, Vera Adema, Kelly S Chien, Sanam Loghavi, Feiyang Ma, Hui Yang, Guillermo Montalban-Bravo, Xuelin Huang, Xavier Calvo, Joby Joseph, Kristy Bodden, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had …

Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome, Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa

Faculty, Staff and Student Publications

No abstract provided.

Addition Of Metastasis-Directed Therapy To Systemic Therapy For Oligometastatic Pancreatic Ductal Adenocarcinoma (Extend): A Multicenter, Randomized Phase Ii Trial, Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang

Faculty, Staff and Student Publications

Purpose: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

Methods: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response …

Dna Methylation Classifier To Diagnose Pancreatic Ductal Adenocarcinoma Metastases From Different Anatomical Sites, Teodor G Calina, Eilís Perez, Elena Grafenhorst, Jamal Benhamida, Simon Schallenberg, Adrian Popescu, Ines Koch, Tobias Janik, Baoqing Chen, Jana Ihlow, Stephanie Roessler, Benjamin Goeppert, Bruno Sinn, Marcus Bahra, George A Calin, Eliane T Taube, Uwe Pelzer, Christopher C M Neumann, David Horst, Erik Knutsen, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

Methods: For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the …

Validation Of A Prognostic Blood-Based Sphingolipid Panel For Men With Localized Prostate Cancer Followed On Active Surveillance, Justin R Gregg, Lisa Newcomb, Ranran Wu, Jennifer Dennison, John W Davis, Curtis Pettaway, Louis Pisters, John F Ward, Brian F Chapin, Lisly Chéry, Ahmet Urkmez, Andrew M Fang, Noel Higgason, Patricia Troncoso, Carrie R Daniel, Christopher Logothetis, Timothy C Thompson, Andrew W Hahn, Menghan Liu, Yingye Zheng, Dan W Lin, Samir Hanash, Ehsan Irajizad, Johannes Fahrmann

Faculty, Staff and Student Publications

Background: We previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.

Methods: Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy. The PASS cohort consisted of 544 patients whereas the MDACC Cohort consisted of 697 …

The Rna Receptor Rig-I Binding Synthetic Oligodeoxynucleotide Promotes Pneumonia Survival, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleóngarcía, Michael K Longmire, Mathilde Lethier, Stephen Cusack, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, …

Ephb4-Rasa1 Inhibition Of Piezo1 Ras Activation Drives Lymphatic Valvulogenesis, Di Chen, Yipei Tang, Philip E Lapinski, David Wiggins, Eva M Sevick, Michael J Davis, Philip D King

Faculty, Staff and Student Publications

BACKGROUND: EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves.

METHODS: We used LV-specific inducible EPHB4-deficient mice and EPHB4 knockin mice that express a form of EPHB4 that is unable to bind RASA1 yet retains protein tyrosine kinase activity (EPHB4 2YP) to study the role of EPHB4 and RASA1 in LV valve development in the embryo and LV …

Daily Diagnostic Quality Computed Tomography-On-Rails (Ctor) Image Guidance For Abdominal Stereotactic Body Radiation Therapy (Sbrt), Rachael M Martin-Paulpeter, P James Jensen, Luis A Perles, Gabriel O Sawakuchi, Prajnan Das, Eugene J Koay, Albert C Koong, Ethan B Ludmir, Joshua S Niedzielski, Sam Beddar

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Stereotactic body radiation therapy (SBRT) for abdominal targets faces a variety of challenges, including motion caused by the respiration and digestion and a relatively poor level of contrast between the tumor and the surrounding tissues. Breath-hold treatments with computed tomography-on-rails (CTOR) image guidance is one way of addressing these challenges, allowing for both the tumor and normal tissues to be well-visualized. Using isodose lines (IDLs) from CT simulations as a guide, the anatomical information can be used to shift the alignment or trigger a replan, such that normal tissues receive acceptable doses of radiation.

METHODS: This study aims to …

Unlocking Intracellular Oncology Targets: The Unique Role Of Antibody-Based T-Cell Receptor Mimic (Tcrm) Therapeutics In T-Cell Engagers (Tces) And Antibody-Drug Conjugates (Adcs), Jeffrey Molldrem, Dongxing Zha

Faculty, Staff and Student Publications

Effectively targeting intracellular tumor-associated proteins presents a formidable challenge in oncology, as they are traditionally considered inaccessible to conventional antibody-based therapies and CAR-T cell therapies. However, recent advancements in antibody engineering have revolutionized this field, offering promising new strategies to combat cancer. This review focuses on the innovative use of T-cell receptor mimic (TCRm) antibodies within the therapeutic frameworks of T-cell engagers (TCE) and antibody-drug conjugates (ADCs). TCRm antibodies, designed to recognize peptide-MHC complexes rather than cell surface proteins, integrate the capacity of T-cells to reach intracellular targets with the unique strengths of antibodies. When incorporated into T-cell engaging therapeutics, …

Real-World Impact Of Differences In The Who And Icc Classifications Of Non-Hodgkin Lymphoma: A Leo Cohort Study Analysis, Brooj Abro, Matthew J Maurer, Thomas M Habermann, W Richard Burack, Jennifer R Chapman, Jonathon B Cohen, Jonathan W Friedberg, Giorgio Inghirami, Brad S Kahl, Melissa C Larson, Brian K Link, Izidore S Lossos, Peter Martin, Timothy J Mcdonnell, Loretta J Nastoupil, Shaun M Riska, Sergei Syrbu, Francisco Vega, Kiran R Vij, Christopher R Flowers, James R Cerhan, David L Jaye, Andrew L Feldman

Faculty, Staff and Student Publications

Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect < 1% of non-Hodgkin lymphomas.

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

Probabilistic Presurgical Language Fmri Atlas Of Patients With Brain Tumors, Jian Ming Teo, Vinodh A Kumar, Jina Lee, Rami W Eldaya, Ping Hou, Mu-Lan Jen, Kyle R Noll, Peng Wei, Sherise D Ferguson, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background and purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials and methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, …

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

Gpr56: Gpcr As A Guardian Against Ferroptosis, Yuelong Yan, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Transmembrane receptor proteins are proficient in sensing external signals and initiating downstream pathways to control cell survival. Lin et al. demonstrated that GPR56, a G-protein-coupled receptor, can be activated by its agonist to suppress ferroptosis-a form of cell death-and effectively mitigate ferroptosis-associated liver damage.

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Jennifer R Landes, Wannes Renders, Laura Muiño Mosquera, Julie De Backer, David W Jantzen, Anji T Yetman, Gisela Teixido-Tura, Arturo Evangelista, Richmond Jeremy, Edward G Jones, Shaine Morris, Tam Doan, Maral Ouzonian, Alan Braverman, Guillaume Jondeau, Olivier Milleron, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) …

Racial And Sociodemographic Disparities In The Use Of Targeted Therapies In Advanced Ovarian Cancer Patients With Medicare, Anne Knisely, Chi-Fang Wu, Alexa Kanbergs, Nuria Agusti, Kirsten A Jorgensen, Alexander Melamed, Sharon H Giordano, Jose Alejandro Rauh-Hain, Roni Nitecki Wilke

Faculty, Staff and Student Publications

Objective: To describe sociodemographic and racial disparities in receipt of poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab among insured patients with ovarian cancer.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients with advanced stage, high grade serous ovarian cancer diagnosed between 2010 and 2019. The primary outcome of interest was receipt of PARPi or bevacizumab at any time after diagnosis. χ2 tests were used to compare categorical variables. Factors independently associated with the receipt of PARPi and/or bevacizumab were identified using a multivariable logistic regression.

Results: The cohort included 6242 patients; 276 …

Obesity And Outcomes In Adoptive Cellular Therapy In Solid Tumors, Derrick L Tao, Mirella Nardo, Cheuk Hong Leung, Heather Y Lin, Lei Kang, Hung Le, Ecaterina E Dumbrava, David S Hong

Faculty, Staff and Student Publications

This cohort study investigates the association of obesity with adoptive cell therapy outcomes in patients with solid tumors.

Patient-Reported Convenience And Effectiveness Of Telehealth For Breast Cancer Management, Akshara Singareeka Raghavendra, Kristofer Jennings, Gil Guerra, Debu Tripathy, Meghan S Karuturi

Faculty, Staff and Student Publications

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, telehealth was rarely used for breast cancer management at tertiary care centers. We sought to examine patient satisfaction, experiences, preferences, and perceived effectiveness and technical quality of telehealth visits in follow-up patients receiving routine outpatient care in the breast medical oncology practice at The University of Texas MD Anderson Cancer Center.

Methods: We administered a survey to 60 follow-up patients for a duration of 9 months (January 5, 2021 to October 27, 2021) who had at least one telehealth consultation during the COVID-19 pandemic, from April 10, 2020 to October 21, 2021. …

Fc-Enhanced Anti-Ctla-4, Anti-Pd-1, Doxorubicin, And Ultrasound-Mediated Blood-Brain Barrier Opening: A Novel Combinatorial Immunotherapy Regimen For Gliomas, Kwang-Soo Kim, Karl Habashy, Andrew Gould, Junfei Zhao, Hinda Najem, Christina Amidei, Ruth Saganty, Víctor A Arrieta, Crismita Dmello, Li Chen, Daniel Y Zhang, Brandyn Castro, Leah Billingham, Daniel Levey, Olivia Huber, Marilyn Marques, David A Savitsky, Benjamin M Morin, Miguel Muzzio, Michael Canney, Craig Horbinski, Peng Zhang, Jason Miska, Surya Padney, Bin Zhang, Raul Rabadan, Joanna J Phillips, Nicholas Butowski, Amy B Heimberger, Jian Hu, Roger Stupp, Dhan Chand, Catalina Lee-Chang, Adam M Sonabend

Faculty, Staff and Student Publications

Background: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers.

Methods: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).

Results: FcE-aCTLA-4 demonstrated high-affinity binding …

Thrombosis, Brain Metastasis Formation, And The Perivascular Metastatic Niche-Novel Insights From The Tumor Microvascular Circulation, Christopher Alvarez-Breckenridge, Priscilla K Brastianos, Daniel P Cahill

Faculty, Staff and Student Publications

No abstract provided.

The Emerging Field Of Viroimmunotherapy For Pediatric Brain Tumors, Marc Garcia-Moure, Virginia Laspidea, Sumit Gupta, Andrew G Gillard, Soumen Khatua, Akhila Parthasarathy, Jiasen He, Frederick F Lang, Juan Fueyo, Marta M Alonso, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the …