Biomedical Informatics Commons^™

The Promise And Future Of Radiomics For Personalized Radiotherapy Dosing And Adaptation, Rachel B Ger, Lise Wei, Issam El Naqa, Jing Wang

Faculty, Staff and Student Publications

Quantitative image analysis, also known as radiomics, aims to analyze large-scale quantitative features extracted from acquired medical images using hand-crafted or machine-engineered feature extraction approaches. Radiomics has great potential for a variety of clinical applications in radiation oncology, an image-rich treatment modality that utilizes computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for treatment planning, dose calculation, and image guidance. A promising application of radiomics is in predicting treatment outcomes after radiotherapy such as local control and treatment-related toxicity using features extracted from pretreatment and on-treatment images. Based on these individualized predictions of treatment outcomes, radiotherapy …

Invited Commentary: Mri Clear Cell Likelihood Score For Indeterminate Solid Renal Masses: Is There A Path For Broad Clinical Adoption?, Ivan Pedrosa

Faculty, Staff and Student Publications

No abstract provided.

Characteristics, Treatment, And Outcome Of Diverticulitis After Immune Checkpoint Inhibitor Treatment In Patients With Malignancies, Austin R Thomas, Mostafa Eyada, Miho Kono, Krishnavathana Varatharajalu, Yang Lu, Guofan Xu, Kavea Panneerselvam, Malek Shatila, Mehmet Altan, Jennifer Wang, John A Thompson, Hao Chi Zhang, Muhammad Ali Khan, Gottumukkala S Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Purpose: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment.

Methods: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups.

Results: 77 eligible patients were included: 63 patients developed …

A Cre Driver Line For Genetic Targeting Of Kappa Opioid Receptor Expressing Cells, Franciely Paliarin, Chelsea Duplantis, Andrea F Jones, Jessica Cucinello-Ragland, Samhita Basavanhalli, Emily Blaze, Evan Doré, Anna Isabella Neel, Haiguo Sun, Rong Chen, Scott Edwards, Nicholas W Gilpin, Robert O Messing, Rajani Maiya

Faculty, Staff and Student Publications

Here we describe the generation and characterization of a Cre knock-in mouse line that harbors a Cre insertion in the 3′UTR of the κ opioid receptor gene (Oprk1) locus and provides genetic access to populations of κ opioid receptor (KOR)-expressing neurons throughout the brain. Using a combination of techniques including RNA in situ hybridization and immunohistochemistry, we report that Cre is expressed with high fidelity in KOR-expressing cells throughout the brain in this mouse line. We also provide evidence that Cre insertion does not alter basal KOR function. Baseline anxiety-like behaviors and nociceptive thresholds are unaltered in Oprk1-Cre …

Transcriptional Profiling And Consensus Molecular Subtype Assignment To Understand Response And Resistance To Anti-Epidermal Growth Factor Receptor Therapy In Colorectal Cancer, Saikat Chowdhury, Ria Gupta, Joshua Millstein, Kangyu Lin, Valsala Haridas, Mohammad A Zeineddine, Christine Parseghian, Heinz-Josef Lenz, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Activating mutations in KRAS, NRAS, and BRAF are known to cause resistance to anti–epidermal growth factor receptor (EGFR) therapy; however, only approximately 40% of patients with colorectal cancer (CRC) with RASWT tumors respond to anti-EGFR treatment. We sought to discover novel biomarkers to predict response to anti-EGFR antibody treatment in CRC and to understand mechanisms of resistance to anti-EGFR therapy.

MATERIALS AND METHODS: Transcriptomic profiles from three clinical and two preclinical cohorts treated with cetuximab were used to assign consensus molecular subtypes (CMS) to each sample and correlated with outcomes.

RESULTS: Restricting to RASWT patients, …

Imaging In Interventional Radiology: 2043 And Beyond, Kristy K Brock, Stephen R Chen, Rahul A Sheth, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Since its inception in the early 20th century, interventional radiology (IR) has evolved tremendously and is now a distinct clinical discipline with its own training pathway. The arsenal of modalities at work in IR includes x-ray radiography and fluoroscopy, CT, MRI, US, and molecular and multimodality imaging within hybrid interventional environments. This article briefly reviews the major developments in imaging technology in IR over the past century, summarizes technologies now representative of the standard of care, and reflects on emerging advances in imaging technology that could shape the field in the century ahead. The role of emergent imaging technologies in …

Federated Benchmarking Of Medical Artificial Intelligence With Medperf, Alexandros Karargyris, Renato Umeton, Micah J Sheller, Alejandro Aristizabal, Johnu George, Anna Wuest, Sarthak Pati, Hasan Kassem, Maximilian Zenk, Ujjwal Baid, Prakash Narayana Moorthy, Alexander Chowdhury, Junyi Guo, Sahil Nalawade, Jacob Rosenthal, David Kanter, Maria Xenochristou, Daniel J Beutel, Verena Chung, Timothy Bergquist, James Eddy, Abubakar Abid, Lewis Tunstall, Omar Sanseviero, Dimitrios Dimitriadis, Yiming Qian, Xinxing Xu, Yong Liu, Rick Siow Mong Goh, Srini Bala, Victor Bittorf, Sreekar Reddy Puchala, Biagio Ricciuti, Soujanya Samineni, Eshna Sengupta, Akshay Chaudhari, Cody Coleman, Bala Desinghu, Gregory Diamos, Debo Dutta, Diane Feddema, Grigori Fursin, Xinyuan Huang, Satyananda Kashyap, Nicholas Lane, Indranil Mallick, Fets Consortium, Brats-2020 Consortium, Ai4safechole Consortium, Pietro Mascagni, Virendra Mehta, Cassiano Ferro Moraes, Vivek Natarajan, Nikola Nikolov, Nicolas Padoy, Gennady Pekhimenko, Vijay Janapa Reddi, G Anthony Reina, Pablo Ribalta, Abhishek Singh, Jayaraman J Thiagarajan, Jacob Albrecht, Thomas Wolf, Geralyn Miller, Huazhu Fu, Prashant Shah, Daguang Xu, Poonam Yadav, David Talby, Mark M Awad, Jeremy P Howard, Michael Rosenthal, Luigi Marchionni, Massimo Loda, Jason M Johnson, Spyridon Bakas, Peter Mattson

Faculty, Staff and Student Publications

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain. MedPerf focuses on enabling federated evaluation of AI models, by securely distributing them to different facilities, such as healthcare organizations. This process of bringing the model …

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing For Craniomaxillofacial Bone Regeneration, Vasudev Vivekanand Nayak, Blaire V Slavin, Edmara T P Bergamo, Andrea Torroni, Christopher M Runyan, Roberto L Flores, F Kurtis Kasper, Simon Young, Paulo G Coelho, Lukasz Witek

Faculty, Staff and Student Publications

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as β-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific …

Bladder-Sparing Treatment In Patients With Bacillus Calmette-Guerin-Unresponsive Non-Muscle-Invasive Bladder Cancer: An Analysis Of Long-Term Survival Outcomes, Wei Shen Tan, Valentina Grajales, Roberto Contieri, Patrick Hensley, Kelly Bree, Pavlos Msaouel, Charles C Guo, Graciela M Nogueras-Gonzalez, Neema Navai, Colin P Dinney, Ashish M Kamat

Faculty, Staff and Student Publications

BACKGROUND: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1-2 yr.

OBJECTIVE: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST.

DESIGN SETTING AND PARTICIPANTS: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated.

INTERVENTION: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS).

RESULTS AND LIMITATIONS: In total, 114 patients with a median follow-up …

First-In-Human Study Of Oleclumab, A Potent, Selective Anti-Cd73 Monoclonal Antibody, Alone Or In Combination With Durvalumab In Patients With Advanced Solid Tumors, Johanna Bendell, Patricia Lorusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison, Minal Barve, Manik Amin, Jayesh Desai, Trisha Wise-Draper, Steven Eck, Yu Jiang, Anis A Khan, Yuling Wu, Philip Martin, Zachary A Cooper, Nairouz Elgeioushi, Nancy Mueller, Rakesh Kumar, Sandip Pravin Patel

Faculty, Staff and Student Publications

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy …

Reducing The Production Of Acrylamide During The Roasting Of Balloon Flower Roots In Consumer Appliances And Industrial Equipment, Min Gyu Lee, Hyebin Han, Seung Hwan Ham, Suyoon Lee, Young Jin Choi, Jungwoo Hahn

Faculty, Staff and Student Publications

This study aimed to determine what conditions were needed to reduce the production of acrylamide when balloon flower roots [Platycodon grandiflorum (Jacq. A. DC.)] were heated. The conditions of temperature, time, and the type of equipment (i.e., consumer appliance or industrial equipment) were the important variables in the experiment. The official criterion for a recommended standard of acrylamide in tea product is less than 1000 µg/kg as determined by the Ministry of Food and Drug Safety in South Korea. A response surface methodology was used to determine whether the heated samples met the safety requirements. The most significant condition …

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline, Anthony Patrizz, Ahmad El Hamamy, Michael Maniskas, Yashasvee Munshi, Louise Atadja, Hilda Ahnstedt, Matthew Howe, Fan Bu, Daniel K Mulkey, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS: Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were …

Severe Arsenic Poisoning Due To Ayurvedic Supplements, Jeremy Hardin, Justin Seltzer, Raymond Suhandynata, Benjamin Spiegel, Robin Silver, Diane Thomas, Henrik Galust, Nathan Friedman, Richard Clark, Jeremiah Momper

Faculty, Staff and Student Publications

Patients that are taking Ayurvedic supplements have an increased risk of heavy metal toxicity. Lead, arsenic, and mercury are frequently identified in these supplements and can cause clinically significant toxicity. Clinicians should screen patients routinely for use of non-pharmaceutical medications and supplements.

The Clinicogenomic Landscape Of Induction Failure In Childhood And Young Adult T-Cell Acute Lymphoblastic Leukemia, David O'Connor, Jonas Demeulemeester, Lucia Conde, Amy Kirkwood, Kent Fung, Foteini Papaleonidopoulou, Gianna Bloye, Nadine Farah, Sunniyat Rahman, Jeremy Hancock, Caroline Bateman, Sarah Inglott, Jon Mee, Javier Herrero, Peter Van Loo, Anthony V Moorman, Ajay Vora, Marc R Mansour

Faculty, Staff and Student Publications

PURPOSE: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).

METHODS: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape.

RESULTS: IF occurred in 10.3% of cases and was significantly associated with increasing age, …

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

Although rates of recombination events across the genome (genetic maps) are fundamental to genetic research, the majority of current studies only use one standard map. There is evidence suggesting population differences in genetic maps, and thus estimating population-specific maps, are of interest. Although the recent availability of biobank-scale data offers such opportunities, current methods are not efficient at leveraging very large sample sizes. The most accurate methods are still linkage disequilibrium (LD)-based methods that are only tractable for a few hundred samples. In this work, we propose a fast and memory-efficient method for estimating genetic maps from population genotyping data. …

Weakly Supervised Spatial Relation Extraction From Radiology Reports, Surabhi Datta, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Weak supervision holds significant promise to improve clinical natural language processing by leveraging domain resources and expertise instead of large manually annotated datasets alone. Here, our objective is to evaluate a weak supervision approach to extract spatial information from radiology reports.

MATERIALS AND METHODS: Our weak supervision approach is based on data programming that uses rules (or labeling functions) relying on domain-specific dictionaries and radiology language characteristics to generate weak labels. The labels correspond to different spatial relations that are critical to understanding radiology reports. These weak labels are then used to fine-tune a pretrained Bidirectional Encoder Representations from …

Histone Demethylase Kdm5d Upregulation Drives Sex Differences In Colon Cancer, Jiexi Li, Zhengdao Lan, Wenting Liao, James W Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A Labella, Chang-Jiun Wu, Kenneth Dunner, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J Spring, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP)2, revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone …

Effect Of Longitudinal Variation In Tumor Volume Estimation For Mri-Guided Personalization Of Breast Cancer Neoadjuvant Treatment, Natsuko Onishi, Teffany Joy Bareng, Jessica Gibbs, Wen Li, Elissa R Price, Bonnie N Joe, John Kornak, Laura J Esserman, David C Newitt, Nola M Hylton, I-Spy 2 Investigator Network

Faculty, Staff and Student Publications

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen …

Dna Methylation-Based Classifier Differentiates Intrahepatic Pancreato-Biliary Tumours, Mihnea P Dragomir, Teodor G Calina, Eilís Perez, Simon Schallenberg, Meng Chen, Thomas Albrecht, Ines Koch, Peggy Wolkenstein, Benjamin Goeppert, Stephanie Roessler, George A Calin, Christine Sers, David Horst, Florian Roßner, David Capper

Faculty, Staff and Student Publications

BACKGROUND: Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task.

METHODS: We assembled genome-wide DNA methylation data for iCCA (n = 259), PAAD (n = 431), and normal bile duct (n = 70) from publicly available sources. We split this cohort into a reference (n = 399) and a validation set (n = 361). Using the reference cohort, we trained three machine learning models to differentiate between these entities. Furthermore, …

Predicting Benefit From Immune Checkpoint Inhibitors In Patients With Non-Small-Cell Lung Cancer By Ct-Based Ensemble Deep Learning: A Retrospective Study, Maliazurina B Saad, Lingzhi Hong, Muhammad Aminu, Natalie I Vokes, Pingjun Chen, Morteza Salehjahromi, Kang Qin, Sheeba J Sujit, Xuetao Lu, Elliana Young, Qasem Al-Tashi, Rizwan Qureshi, Carol C Wu, Brett W Carter, Steven H Lin, Percy P Lee, Saumil Gandhi, Joe Y Chang, Ruijiang Li, Michael F Gensheimer, Heather A Wakelee, Joel W Neal, Hyun-Sung Lee, Chao Cheng, Vamsidhar Velcheti, Yanyan Lou, Milena Petranovic, Waree Rinsurongkawong, Xiuning Le, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y Elamin, Marcelo V Negrao, Ferdinandos Skoulidis, Carl M Gay, Tina Cascone, Mara B Antonoff, Boris Sepesi, Jeff Lewis, Ignacio I Wistuba, John D Hazle, Caroline Chung, David Jaffray, Don L Gibbons, Ara Vaporciyan, J Jack Lee, John V Heymach, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context.

METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from …

Effects Of A School-Based Gardening, Cooking, And Nutrition Cluster Randomized Controlled Trial On Unprocessed And Ultra-Processed Food Consumption, Matthew R Jeans, Matthew J Landry, Sarvenaz Vandyousefi, Erin A Hudson, Marissa Burgermaster, Molly S Bray, Joya Chandra, Jaimie N Davis

Faculty, Staff and Student Publications

BACKGROUND: School-based gardening and nutrition education interventions report improvements in dietary intake, notably through fruit and vegetables. However, gardening, cooking, and nutrition randomized controlled trials are limited in evaluating dietary quality, and none have examined processed food consumption to date.

OBJECTIVES: The study examined the effects of Texas Sprouts (TX Sprouts), a gardening, cooking, and nutrition education intervention, compared with control on unprocessed and ultra-processed food (UPF) consumption in predominately low-income Hispanic children.

METHODS: TX Sprouts was a school-based cluster randomized controlled trial that consisted of 16 elementary schools randomly assigned to either the TX Sprouts intervention (n = 8 …

Who, Where, When: Colorectal Cancer Disparities By Race And Ethnicity, Subsite, And Stage, Kristin M Primm, Andrea Joyce Malabay, Taylor Curry, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: There are well-established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited.

METHODS: The Surveillance, Epidemiology, and End Results database identified patients aged 50-74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age-adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox …

Author Correction: Multiscale Reorganization Of The Genome Following Dna Damage Facilitates Chromosome Translocations Via Nuclear Actin Polymerization, Jennifer Zagelbaum, Allana Schooley, Junfei Zhao, Benjamin R Schrank, Elsa Callen, Shan Zha, Max E Gottesman, André Nussenzweig, Raul Rabadan, Job Dekker, Jean Gautier

Faculty, Staff and Student Publications

No abstract provided.

Venetoclax Consolidation In High-Risk Cll Treated With Ibrutinib For ≥1 Year Achieves A High Rate Of Undetectable Mrd, Philip A Thompson, Michael J Keating, Alessandra Ferrajoli, Nitin Jain, Christine B Peterson, Naveen Garg, Sa A Wang, Jeffrey L Jorgensen, Tapan M Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J Short, William G Wierda

Faculty, Staff and Student Publications

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10−4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were …

Single-Cell Profiling Of Tumor Immune Microenvironment Reveals Immune Irresponsiveness In Gastric Signet-Ring Cell Carcinoma, Jing Chen, Kuai Liu, Yikai Luo, Muxing Kang, Jun Wang, Guofeng Chen, Jia Qi, Wenxuan Wu, Beidi Wang, Yaxuan Han, Le Shi, Kefan Wang, Xiaying Han, Xiaojing Ma, Wei Liu, Yuan Ding, Liangjing Wang, Han Liang, Lie Wang, Jian Chen

Faculty, Staff and Student Publications

Background & aims: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes.

Methods: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody …

Early Stage Gastric Adenocarcinoma: Clinical And Molecular Landscapes, Yuki Hirata, Ayesha Noorani, Shumei Song, Linghua Wang, Jaffer A Ajani

Faculty, Staff and Student Publications

Gastric adenocarcinoma, even when diagnosed at an early (localized) disease stage, poses a major health-care burden with cure rates that remain unsatisfactorily low, particularly in Western countries. This lack of progress reflects, among other aspects, the impracticality of early diagnosis, considerable variations in therapeutic approaches that is partly based on regional preferences, and the ingrained heterogeneity of gastric adenocarcinoma cells and their associated tumour microenvironment (TME). Clinical trials have long applied empirical interventions with the assumption that all early stage gastric adenocarcinomas are alike. Despite certain successes, the shortcomings of these approaches can potentially be overcome by targeting the specific …

Neoadjuvant Immunotherapy For Advanced, Resectable Non-Small Cell Lung Cancer: A Systematic Review And Meta-Analysis, Yajing Wu, Vivek Verma, Carl M Gay, Yujia Chen, Fei Liang, Qiang Lin, Jianing Wang, Wei Zhang, Zhouguang Hui, Min Zhao, Jun Wang, Joe Y Chang

Faculty, Staff and Student Publications

Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.

Methods: Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

Transplantation Referral Patterns For Patients With Newly Diagnosed Higher-Risk Myelodysplastic Syndromes And Acute Myeloid Leukemia At Academic And Community Sites In The Connect® Myeloid Disease Registry: Potential Barriers To Care, Benjamin Tomlinson, Marcos De Lima, Christopher R Cogle, Michael A Thompson, David L Grinblatt, Daniel A Pollyea, Rami S Komrokji, Gail J Roboz, Michael R Savona, Mikkael A Sekeres, Mehrdad Abedi, Guillermo Garcia-Manero, Sandra E Kurtin, Jaroslaw P Maciejewski, Jay L Patel, Dennis A Revicki, Tracy I George, E Dawn Flick, Pavel Kiselev, Chrystal U Louis, Irene S Degutis, Melissa Nifenecker, Harry P Erba, David P Steensma, Bart L Scott

Faculty, Staff and Student Publications

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to …