Biomedical Informatics Commons^™

Clinical Practice Guidelines For The Care Of Girls And Women With Turner Syndrome, Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A Van Der Velden, International Turner Syndrome Consensus Group, Philippe F Backeljauw

Faculty, Staff and Student Publications

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

METHODS: The study uses a two by three factorial design. …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

Methods: The study uses a two by three factorial design. …

Piga Mutations And Glycosylphosphatidylinositol Anchor Dysregulation In Polyposis-Associated Duodenal Tumorigenesis, Elena Meuser, Kyle Chang, Angharad Walters, Joanna J Hurley, Hannah D West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T Williams, Melissa W Taggart, Kim Luetchford, Patrick M Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K Clark, Julian R Sampson, Eduardo Vilar, Laura E Thomas

Faculty, Staff and Student Publications

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of …

Orthogonal Proteogenomic Analysis Identifies The Druggable Pa2g4-Myc Axis In 3q26 Aml, Matteo Marchesini, Andrea Gherli, Elisa Simoncini, Lucas Moron Dalla Tor, Anna Montanaro, Natthakan Thongon, Federica Vento, Chiara Liverani, Elisa Cerretani, Anna D'Antuono, Luca Pagliaro, Raffaella Zamponi, Chiara Spadazzi, Elena Follini, Benedetta Cambò, Mariateresa Giaimo, Angela Falco, Gabriella Sammarelli, Giannalisa Todaro, Sabrina Bonomini, Valentina Adami, Silvano Piazza, Claudia Corbo, Bruno Lorusso, Federica Mezzasoma, Costanza Anna Maria Lagrasta, Maria Paola Martelli, Roberta La Starza, Antonio Cuneo, Franco Aversa, Cristina Mecucci, Federico Quaini, Simona Colla, Giovanni Roti

Faculty, Staff and Student Publications

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, here we dissect the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstitute the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 (PA2G4) protein. PA2G4 overexpression rescues AML cells from the …

Semirecumbent Positioning During Anesthesia Recovery And Postoperative Hypoxemia: A Randomized Clinical Trial, Xinghe Wang, Kedi Guo, Jia Sun, Yuping Yang, Yan Wu, Xihui Tang, Yuqing Xu, Qingsong Chen, Si Zeng, Liwei Wang, Su Liu

Faculty, Staff and Student Publications

IMPORTANCE: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use.

OBJECTIVE: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete.

INTERVENTIONS: Patients were randomized to 1 of the following positions at the end of the operation until leaving the …

Primary Cytoreduction And Survival For Patients With Less-Common Epithelial Ovarian Cancer, Koji Matsuo, Ling Chen, Maximilian Klar, Lynda D Roman, Anil K Sood, David M Gershenson, Jason D Wright

Faculty, Staff and Student Publications

This cohort study examines the association between primary cytoreduction status and survival for patients with less-common, advanced-stage epithelial ovarian carcinoma.

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

Maintenance Pembrolizumab Therapy In Patients With Metastatic Her2-Negative Breast Cancer With Prior Response To Chemotherapy, Toshiaki Iwase, Evan N Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel M Layman, David L Ramirez, Debasish Tripathy, Stacy L Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M Reuben, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study.

Patients and methods: Patients with a complete response, partial response, or stable disease (SD) after at least three cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 …

Cell-Free Dna Concentration As A Biomarker Of Response And Recurrence In Her2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy, Mark Jesus M Magbanua, Ziad Ahmed, Rosalyn W Sayaman, Lamorna Brown Swigart, Gillian L Hirst, Christina Yau, Denise M Wolf, Wen Li, Amy L Delson, Jane Perlmutter, Paula Pohlmann, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J Esserman, Angela M Demichele, Hope S Rugo, Laura J Van 'T Veer

Faculty, Staff and Student Publications

Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.

Experimental design: 145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.

Results: In TNBC, we observed a modest negative correlation between cfDNA concentration 3 …

Efficacy And Safety Of Adagrasib Plus Cetuximab In Patients With Krasg12c-Mutated Metastatic Colorectal Cancer, Rona Yaeger, Nataliya V Uboha, Meredith S Pelster, Tanios S Bekaii-Saab, Minal Barve, Joel Saltzman, Joshua K Sabari, Julio A Peguero, Andrew Scott Paulson, Pasi A Jänne, Marcia Cruz-Correa, Kenna Anderes, Karen Velastegui, Xiaohong Yan, Hirak Der-Torossian, Samuel J Klempner, Scott E Kopetz

Faculty, Staff and Student Publications

Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2-7.6). Median progression-free survival was 6.9 months …

Irx4204 Induces Senescence And Cell Death In Her2-Positive Breast Cancer And Synergizes With Anti-Her2 Therapy, Cassandra L Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E Sanders, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, …

Radiogenomics-Based Risk Prediction Of Glioblastoma Multiforme With Clinical Relevance, Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D Chan, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed …

Antibiotic Bone Cement Accelerates Diabetic Foot Wound Healing-Elucidating The Role Of Rock1 Protein Expression, Liang Li, Guangming Zhang, Yanwei Sun

Faculty, Staff and Student Publications

No abstract provided.

Associations Between Longer Leukocyte Telomere Length And Increased Lung Cancer Risk Among Never Smokers In Urban China, Jason Y Y Wong, Xiao-Ou Shu, Wei Hu, Batel Blechter, Jianxin Shi, Kevin Wang, Richard Cawthon, Qiuyin Cai, Gong Yang, Mohammad L Rahman, Bu-Tian Ji, Yutang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology.

METHODS: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control …

Enhancing Foot Care Education And Support Strategies In Adults With Type 2 Diabetes, Hsiao-Hui Ju, Madelene Ottosen, Jeffery Alford, Jed Jularbal, Constance Johnson

Faculty, Staff and Student Publications

BACKGROUND: People with diabetes are susceptible to serious and disabling foot complications, which increase their morbidity and mortality rates. Examining the perspectives of people with diabetes on their foot care routines could help elucidate their beliefs and offer practical ways to prevent foot problems.

PURPOSE: We explored the perspectives of adults with diabetes on their foot care practices to identify and enhance foot care education and support strategies.

METHODOLOGY: Using the Zoom platform, 29 adults with diabetes completed a 3-month telehealth educational program, during which interviews were conducted. This article reports the results of thematic content analysis of the qualitative …

A Prismatic View Of The Epigenetic-Metabolic Regulatory Axis In Breast Cancer Therapy Resistance, Chandrima Das, Apoorva Bhattacharya, Swagata Adhikari, Atanu Mondal, Payel Mondal, Santanu Adhikary, Siddhartha Roy, Kenneth Ramos, Kamlesh K Yadav, John A Tainer, Tej K Pandita

Faculty, Staff and Student Publications

Epigenetic regulation established during development to maintain patterns of transcriptional expression and silencing for metabolism and other fundamental cell processes can be reprogrammed in cancer, providing a molecular mechanism for persistent alterations in phenotype. Metabolic deregulation and reprogramming are thus an emerging hallmark of cancer with opportunities for molecular classification as a critical preliminary step for precision therapeutic intervention. Yet, acquisition of therapy resistance against most conventional treatment regimens coupled with tumor relapse, continue to pose unsolved problems for precision healthcare, as exemplified in breast cancer where existing data informs both cancer genotype and phenotype. Furthermore, epigenetic reprograming of the …

Understanding The Treatment Paradigm And The Sequencing Of Antiglaucoma Fixed-Dose Combinations In A Tertiary Center In South India, Ronnie George, Praggya Mishra, Balekudaru Shantha, Lingam Vijaya, Nitin Maksane, Neha Gurha

Faculty, Staff and Student Publications

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India.

METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications …

Longitudinal Changes In The Carotid Arteries Of Head And Neck Cancer Patients Following Radiation Therapy: Results From A Prospective Serial Imaging Biomarker Characterization Study, Efstratios Koutroumpakis, Abdallah Sherif Radwan Mohamed, Peter Chaftari, David I Rosenthal, Dorothy Gujral, Christopher Nutting, Serageldin Kamel, Mohamed A Naser, Peter Kim, Roland Bassett, Clifton D Fuller, Elie Mouhayar, Md Anderson Head Neck Radiation Oncology Cardiovascular Working Group

Faculty, Staff and Student Publications

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; …

A Phase I Study Of Tak-659 And Paclitaxel In Patients With Taxane-Refractory Advanced Solid Tumors, M A Gouda, J Shunyakova, A Naing, E Dumbrava, D S Hong, Y Yuan, P Yang, A Myers, Y Liang, J Peng, D Karp, A M Tsimberidou, J Rodon, T A Yap, S A Piha-Paul, F Meric-Bernstam, S Fu

Faculty, Staff and Student Publications

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.

PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients …

Unswitched Memory B Cell Deficiency In Children With Sickle Cell Disease And Response To Pneumococcal Polysaccharide Vaccine, Venée N Tubman, Daniel Maysonet, Norma Estrada, Tripti Halder, Lindsey Ramos, Sameera Bhamidipati, Alexandre F Carisey, Charles G Minard, Carl E Allen

Faculty, Staff and Students Publications

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with …

Hyperkinetic Movement Disorder Caused By The Recurrent C892c>T Nacc1 Variant, Jonna Komulainen-Ebrahim, Salla M Kangas, Estrella López-Martín, Timothy Feyma, Fernando Scaglia, Beatriz Martínez-Delgado, Outi Kuismin, Maria Suo-Palosaari, Lucinda Carr, Reetta Hinttala, Manju A Kurian, Johanna Uusimaa

Faculty, Staff and Students Publications

BACKGROUND: Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.

OBJECTIVES: The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.

METHODS: The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function …

Associations Between Radiation Oncologist Demographic Factors And Segmentation Similarity Benchmarks: Insights From A Crowd-Sourced Challenge Using Bayesian Estimation, Kareem A Wahid, Onur Sahin, Suprateek Kundu, Diana Lin, Anthony Alanis, Salik Tehami, Serageldin Kamel, Simon Duke, Michael V Sherer, Mathis Rasmussen, Stine Korreman, David Fuentes, Michael Cislo, Benjamin E Nelms, John P Christodouleas, James D Murphy, Abdallah S R Mohamed, Renjie He, Mohammed A Naser, Erin F Gillespie, Clifton D Fuller

Faculty, Staff and Student Publications

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors.

METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference …

Genome-Wide Interaction Study Of Dietary Intake Of Fibre, Fruits, And Vegetables With Risk Of Colorectal Cancer, Nikos Papadimitriou, Andre Kim, Eric S Kawaguchi, John Morrison, Virginia Diez-Obrero, Demetrius Albanes, Sonja I Berndt, Stéphane Bézieau, Stephanie A Bien, D Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Daniel D Buchanan, Peter T Campbell, Robert Carreras-Torres, Andrew T Chan, Jenny Chang-Claude, David V Conti, Matthew A Devall, Niki Dimou, David A Drew, Stephen B Gruber, Tabitha A Harrison, Michael Hoffmeister, Jeroen R Huyghe, Amit D Joshi, Temitope O Keku, Anshul Kundaje, Sébastien Küry, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M Lynch, Victor Moreno, Christina C Newton, Mireia Obón-Santacana, Jennifer Ose, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, Conghui Qu, Gad Rennert, Edward Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Yu-Ru Su, Duncan C Thomas, Claire E Thomas, Yu Tian, Konstantinos K Tsilidis, Cornelia M Ulrich, Caroline Y Um, Kala Visvanathan, Jun Wang, Emily White, Michael O Woods, Stephanie L Schmit, Finlay Macrae, John D Potter, John L Hopper, Ulrike Peters, Neil Murphy, Li Hsu, Marc J Gunter, W James Gauderman

Faculty, Staff and Student Publications

Background: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations.

Methods: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction …

High Community-Level Social Vulnerability Is Associated With Worse Recurrence-Free Survival (Rfs) After Resection Of Extremity And Truncal Soft Tissue Sarcoma, Raymond S Traweek, Heather G Lyu, Russell G Witt, Rebecca A Snyder, Elise F Nassif, David D Krijgh, Jeffrey M Smith, Gordon S Tilney, Chun Feng, Yi-Ju Chiang, Keila E Torres, Margaret J Roubaud, Christopher P Scally, Kelly K Hunt, Emily Z Keung, Alexander F Mericli, Christina L Roland

Faculty, Staff and Student Publications

Background: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes.

Methods: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and …

Evaluations Of An Early Change In Tumor Pathophysiology In Response To Radiotherapy With Oxygen Enhanced Electron Paramagnetic Resonance Imaging (Oe Epri), Tianzhe Li, Grace A Murley, Xiaofei Liang, Renee L Chin, Jorge De La Cerda, F William Schuler, Mark D Pagel

Faculty, Staff and Student Publications

Purpose: Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO2) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO2 with breathing gases of 21% O2 (pO221%) and 100% O2 (pO2100%), and the differences in pO2 between breathing gases (ΔpO2). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.

Procedures: We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we …

Characteristics And Outcomes Of Acute Myeloid Leukaemia Patients With Baseline Cd7 Expression, Wei-Ying Jen, Koji Sasaki, Sanam Loghavi, Sa A Wang, Wei Qiao, Gautam Borthakur, Farhad Ravandi, Tapan M Kadia, Ghayas C Issa, Nicholas J Short, Musa Yilmaz, Naval G Daver, Courtney D Dinardo

Faculty, Staff and Student Publications

Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7-15.9] vs. 19.0 months [95% CI, 16.1-23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability …

Ivosidenib Significantly Reduces Triazole Levels In Patients With Acute Myeloid Leukemia And Myelodysplastic Syndrome, Ashley Dinh, J Michael Savoy, Dimitrios P Kontoyiannis, Koichi Takahashi, Ghayas C Issa, Hagop M Kantarjian, Courtney D Dinardo, Caitlin R Rausch

Faculty, Staff and Student Publications

Background: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations. Although posaconazole is a substrate of P-glycoprotein, it is metabolized primarily via UDP glucuronidation; thus, the impact of ivosidenib on posaconazole exposure is unknown.

Methods: Patients treated with ivosidenib and concomitant triazole with at least one …

Outcome Of Patients With Relapsed Acute Promyelocytic Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney D Dinardo, Musa Yilmaz, Nicholas Short, Elias Jabbour, Keyur P Patel, Sanam Loghavi, Sherry Pierce, Gautam Borthakur, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The outcome of patients with acute promyelocytic leukemia (APL) has improved significantly since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as APL therapies. The optimal therapy for APL relapse is believed to require autologous or allogeneic stem cell transplantation (SCT) based on historical experience.

Study aims: To evaluate the outcome of patients with relapsed APL before and after the era of ATRA-ATO.

Patients and methods: We reviewed 61 patients with relapsed APL treated from November 1991 to June 2023; 31 patients (51%) received modern therapy with the combination of ATRA and ATO with and without …

Plasmacytoid Urothelial Carcinoma Of The Urinary Bladder-A Clinicopathological And Molecular Analysis Of 52 Cases, Lan Zheng, Hui Chen, Jianping Zhao, Sinchita Roy-Chowdhuri, Ashish M Kamat, Omar Alhalabi, Jianjun Gao, Arlene Siefker-Radtke, Donna E Hansel, Bogdan Czerniak, Charles C Guo

Faculty, Staff and Student Publications

Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41-91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5-100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n …