Digital Commons Network^™

Development And Validation Of An Interpretable Longitudinal Preeclampsia Risk Prediction Using Machine Learning, Braden W Eberhard, Raphael Y Cohen, Nolan Wheeler, Ricardo Kleinlein, John Rigoni, David W Bates, Kathryn J Gray, Vesela P Kovacheva

Faculty, Staff and Students Publications

Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension after 20 weeks of gestation that affects 2-8% of all pregnancies and contributes to up to 26% of maternal deaths. Despite extensive clinical research, current predictive tools fail to identify up to 66% of patients who develop preeclampsia. We sought to develop a tool to longitudinally predict preeclampsia risk. In this retrospective model development and validation study, we examined a large cohort of patients who delivered at three hospitals in the New England region between 05/2015 and 05/2023. We used sociodemographic, clinical diagnoses, family history, laboratory, and vital signs data. …

Incorporating Individually Defined Brain Health Priorities In Clinical Trial Outcomes: The Electronic Person-Specific Outcome Measure Approach In The United States, Stina Saunders, Ali Jannati, Shane Sheehan, Claudio Toro-Serey, Sean Tobyne, Killian Mcmanus, David Bates, John Showalter, Álvaro Pascual-Leone

Faculty, Staff and Students Publications

Introduction: While a limited number of disease-modifying treatments for Alzheimer's disease (AD) have been approved in the United States, there is caution in adopting these treatments in clinical use. The electronic Person-Specific Outcome Measure (ePSOM) tool was recently developed to establish whether, besides modifying underlying AD pathology, new treatments exerted sufficient beneficial effects in areas that matter the most to an individual.

Methods: We conducted a study to understand how findings from the ePSOM UK study applied in the United States. The ePSOM US survey (May 2023 to January 2024) collected primarily free-text responses in personally defined brain health priorities, …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Jennifer A Belsky, Ashley Chavana, Ankona Banerjee, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

The Utility Of Brain Biomarkers In Predicting Survival And Neurological Outcomes In Pediatric Patients After Cardiac Arrest: A Systematic Review And Meta-Analysis, Halla Kamińska, Krzysztof Kurek, Michał Zembala, Sagar Galwankar, Monika Tomaszewska, Shraddha Singh, Nicola Luigi Bragazzi, Michał Pruc, Basar Cander, Francesco Chirico, Amelia Rizzo, Jacek Kubica, Ayman El-Menyar, Anne Lepetit, Pawel Patrzylas, Zubaid Rafique, W Frank Peacock, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Cardiac arrest in children is associated with high morbidity and mortality, primarily due to neurological injury. Biomarkers linked to brain injury, released into circulation from compromised elements of the neurovascular unit, act as significant prognostic indicators in patients suffering from hypoxic-ischemic brain injury (HIBI) subsequent to the restoration of spontaneous circulation (ROSC) after pediatric cardiac arrest. The aim of this systematic review and meta-analysis is to evaluate the prognostic utility of brain injury biomarkers in predicting neurological outcomes and survival in patients following cardiac arrest in the pediatric population.

Methods: Bibliographic databases (PubMed, the Cochrane Library, and Embase) were …

Diagnostic And Prognostic Value Of Cystatin C In Acute Coronary Syndrome: An Up-To-Date Meta-Analysis, Michal Pruc, Damian Swieczkowski, Basar Cander, Milosz J Jaguszewski, Sagar Galwankar, Salvatore Di Somma, Fatimah Lateef, Indrani Sardesai, Ayman El-Menyar, Michal Zembala, Jacek Kubica, Togay Evrin, Burak Katipoglu, Zubaid Rafique, Frank William Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

Background: The role of Cystatin C (CysC) in the diagnosis and prognosis of cardiovascular disease, particularly acute coronary syndrome (ACS), is increasingly significant. The goal of this meta-analysis was to assess the diagnostic and prognostic value of CysC in patients with ACS, as well as its association with major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction, heart failure, and stroke.

Methods: The present study is a systematic review and meta-analysis. Using PubMed, Web of Science, Cochrane Library, and Embase, a literature review of cohort and case control studies reporting MACE and using the terms ACS and Cystatin C …

Prognostic Value Of The Monocyte-To-High-Density Lipoprotein-Cholesterol Ratio In Acute Coronary Syndrome Patients: A Systematic Review And Meta-Analysis, Michał Pruc, Jacek Kubica, Maciej Banach, Damian Świeczkowski, Zubaid Rafique, William Frank Peacock, Zbigniew Siudak, Stanisław Surma, Prabath Nanayakkara, Krzysztof Kurek, Anne Lepetit, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Globally, diseases of the cardiovascular system stand as principal contributors to mortality and are expected to show an upward trajectory. The occurrence of acute coronary syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS.

Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients.

Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses published before February 26, …

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

Faculty, Staff and Student Publications

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

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

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Acute Myeloid Leukemia Management And Research In 2025, Hagop M Kantarjian, Courtney D Dinardo, Tapan M Kadia, Naval G Daver, Jessica K Altman, Eytan M Stein, Elias Jabbour, Charles A Schiffer, Amy Lang, Farhad Ravandi

Faculty, Staff and Student Publications

The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 …

Exercise And Nutrition To Improve Cancer Treatment-Related Outcomes (Enicto), Kathryn H Schmitz, Justin C Brown, Melinda L Irwin, Kim Robien, Jessica M Scott, Nathan A Berger, Bette Caan, Andrea Cercek, Tracy E Crane, Scott R Evans, Jennifer A Ligibel, Jeffrey A Meyerhardt, Tanya Agurs-Collins, Karen Basen-Engquist, Jennifer W Bea, Sheng F Cai, Brenda Cartmel, Vernon M Chinchilli, Wendy Demark-Wahnefried, Christina M Dieli-Conwright, Loretta Dipietro, Shawna E Doerksen, Sharon L Edelstein, Joanne Elena, William Evans, Leah M Ferrucci, Julia Foldi, Sarah Freylersythe, Helena Furberg, Lee W Jones, Ross Levine, Chaya S Moskowitz, Cynthia Owusu, Frank Penedo, Borsika A Rabin, Elena Ratner, Margaret Rosenzweig, Talya Salz, Tara Sanft, Matthew Schlumbrecht, Guillaume Spielmann, Cynthia A Thomson, Ashley H Tjaden, Martin R Weiser, Shengping Yang, Anthony F Yu, Frank M Perna, Enicto Consortium

Faculty, Staff and Student Publications

Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

International Multicenter Retrospective Study From The Ultra-Rare Sarcoma Working Group On Low-Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, And Hybrid Forms: Outcome Of Primary Localized Disease, Claudia Giani, Abdulazeez Salawu, Silva Ljevar, Ryan A Denu, Andrea Napolitano, Emanuela Palmerini, Elizabeth A Connolly, Koichi Ogura, Daniel D Wong, Roberto Scanferla, Evan Rosenbaum, Jyoti Bajpai, Zola Chia-Chen Li, Susie Bae, Lorenzo D'Ambrosio, Steve Bialick, Andrew J Wagner, Alexander T J Lee, Hanna Koseła-Paterczyk, Giacomo G Baldi, Antonella Brunello, Yeh Chen Lee, Herbert H Loong, Sosipatros Boikos, Fernando Campos, Carlo M Cicala, Robert G Maki, Nadia Hindi, Costanza Figura, Shahd S Almohsen, Sheyaskumar Patel, Robin L Jones, Toni Ibrahim, Rooshdiya Karim, Akira Kawai, Richard Carey-Smith, Richard Boyle, Silvia M Taverna, Alexander J Lazar, Elizabeth G Demicco, Judith V M G Bovee, Angelo P Dei Tos, Christopher Fletcher, Daniel Baumhoer, Marta Sbaraglia, Inga-Marie Schaefer, Rosalba Miceli, Alessandro Gronchi, Silvia Stacchiotti

Faculty, Staff and Student Publications

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. …

Histopathologic Progression And Metastatic Relapse Outcomes In Small Cell Neuroendocrine Carcinomas Of The Urinary Tract, Mohammad Jad Moussa, Georges C Tabet, Arlene O Siefker-Radtke, Lianchun Xiao, Nathaniel R Wilson, Jianjun Gao, Christopher J Logothetis, Petros Grivas, Byron Lee, Amishi Y Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M Tannir, Ashish M Kamat, Donna E Hansel, Charles C Guo, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Student Publications

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials and methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

Results: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) …

Outcomes Of Patients Treated With Chemotherapy For Breast Cancer During Pregnancy Compared With Nonpregnant Breast Cancer Patients Treated With Systemic Therapy, Helen M Johnson, Juhee Song, Carla L Warneke, Ashley L Martinez, Jennifer K Litton, Oluchi C Oke

Faculty, Staff and Student Publications

Introduction: Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype.

Methods: PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible. Disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression.

Results: Among 143 PrBC and 285 nonpregnant patients, median follow-up was 11.4 years. …

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

Faculty, Staff and Student Publications

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

Outcomes With Bridging Radiation Therapy Prior To Chimeric Antigen Receptor T-Cell Therapy In Patients With Aggressive Large B-Cell Lymphomas, Gohar S Manzar, Chelsea C Pinnix, Stephanie O Dudzinski, Kathryn E Marqueen, Elaine E Cha, Lewis F Nasr, Alison K Yoder, Michael K Rooney, Paolo Strati, Sairah Ahmed, Chijioke Nze, Ranjit Nair, Luis E Fayad, Michael Wang, Loretta J Nastoupil, Jason R Westin, Christopher R Flowers, Sattva S Neelapu, Jillian R Gunther, Bouthaina S Dabaja, Susan Y Wu, Penny Q Fang

Faculty, Staff and Student Publications

Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.

Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney …

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Patterns Of Loco-Regional Progression And Patient Outcomes After Definitive-Dose Radiation Therapy For Anaplastic Thyroid Cancer, Julianna K Bronk, Alexander Augustyn, Abdallah S R Mohamed, C David Fuller, Adam S Garden, Amy C Moreno, Anna Lee, William H Morrison, Jack Phan, Jay P Reddy, David I Rosenthal, Michael T Spiotto, Steven J Frank, Ramona Dadu, Naifa Busaidy, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Renata Ferrarotto, Priyanka C Iyer, Maria E Cabanillas, G Brandon Gunn

Faculty, Staff and Student Publications

Background: The aim of this study is to characterize the patterns of loco-regional progression (LRP) and outcomes after definitive-dose intensity modulated radiation therapy (IMRT) for anaplastic thyroid cancer (ATC) with macroscopic neck disease at the time of IMRT.

Methods: Disease/treatment characteristics and outcomes for patients with unresected or incompletely resected ATC who received IMRT (≥45 Gy) were retrospectively reviewed. For those with LRP after IMRT, progressive/recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration. rGTVs were classified based on established spatial/dosimetric criteria.

Results: Forty patients treated between 2010-2020 formed …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Dedifferentiated Liposarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Experience, Madeline B Torres, Cheuk Hong Leung, Marianne Zoghbi, Rossana Lazcano, Davis Ingram, Khalida Wani, Emily Z Keung, M Alejandra Zarzour, Christopher P Scally, Kelly K Hunt, Anthony Conley, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan Farooqi, Devarati Mitra, Alison K Yoder, Michael S Nakazawa, Dejka Araujo, Andrew Livingston, Ravin Ratan, Shreyaskumar Patel, Vinod Ravi, Alexander J Lazar, Christina L Roland, Neeta Somaiah, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center.

Methods: We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Different Phenotypes With Different Endings-Telomere Biology Disorders And Cancer Predisposition With Long Telomeres, Sharon A Savage, Alison A Bertuch, Team Telomere And The Clinical Care Consortium For Telomere‐Associated Ailments (Ccctaa)

Faculty, Staff and Students Publications

Rare germline pathogenic variants (GPVs) in genes essential in telomere length maintenance and function have been implicated in two broad classes of human disease. The telomere biology disorders (TBDs) are a spectrum of life-threatening conditions, including bone marrow failure, liver and lung disease, cancer and other complications caused by GPVs in telomere maintenance genes that result in short and/or dysfunctional telomeres and reduced cellular replicative capacity. In contrast, cancer predisposition with long telomeres (CPLT) is a disorder associated with elevated risk of a variety of cancers, primarily melanoma, thyroid cancer, sarcoma, glioma and lymphoproliferative neoplasms caused by GPVs in shelterin …

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Efficacy Of A Smartphone Application Assisting Home-Based Rehabilitation And Symptom Management For Patients With Lung Cancer Undergoing Video-Assisted Thoracoscopic Lobectomy: A Prospective, Single-Blinded, Randomised Control Trial (Popper Study, Chao Lv, Fangliang Lu, Xiugeng Zhou, Xiang Li, Wenhua Yu, Chune Zhang, Kaishen Chen, Songtao Du, Chao Han, Jia Wang, Yuzhao Wang, Shaolei Li, Liang Wang, Yinan Liu, Shanyuan Zhang, Miao Huang, Dongdong Song, Dachuan Zhao, Bing Liu, Yaqi Wang, Xinrun Cui, Zhiwei Zhou, Shi Yan, Nan Wu

Faculty, Staff and Student Publications

Background: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and postdischarge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation.

Methods: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. The authors screened 265 patients …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …