Medical Specialties Commons^™

Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Opeyemi A Jagede, Kevin Tuballes, Diane M Del Valle, Geoffrey Kelly, Manishkumar Patel, Hui Xie, Jocelyn Harris, Kimberly Argueta, Kai Nie, Vanessa Barcessat, Radim Moravec, Jennifer Altreuter, Dzifa Y Duose, Brad S Kahl, Stephen M Ansell, Joyce Yu, Ethan Cerami, James R Lindsay, Ignacio I Wistuba, Seunghee Kim-Schulze, Catherine S Diefenbach, Sacha Gnjatic

Faculty, Staff and Student Publications

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a …

Multicenter Analysis Of Valganciclovir Prophylaxis In Pediatric Solid Organ Transplant Recipients, Marc Foca, Salih Demirhan, Flor M Munoz, Kristen G Valencia Deray, Claire E Bocchini, Tanvi S Sharma, Gilad Sherman, William J Muller, Taylor Heald-Sargent, Lara Danziger-Isakov, Samantha Blum, Juri Boguniewicz, Samantha Bacon, Tuhina Joseph, Jodi Smith, Monica I Ardura, Yin Su, Gabriela M Maron, Jose Ferrolino, Betsy C Herold

Faculty, Staff and Students Publications

BACKGROUND: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

METHODS: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models.

RESULTS: Among the …

Acute Kidney Injury In Patients With Cirrhosis: Acute Disease Quality Initiative (Adqi) And International Club Of Ascites (Ica) Joint Multidisciplinary Consensus Meeting, Mitra K Nadim, John A Kellum, Lui Forni, Claire Francoz, Sumeet K Asrani, Marlies Ostermann, Andrew S Allegretti, Javier A Neyra, Jody C Olson, Salvatore Piano, Lisa B Vanwagner, Elizabeth C Verna, Ayse Akcan-Arikan, Paolo Angeli, Justin M Belcher, Scott W Biggins, Akash Deep, Guadalupe Garcia-Tsao, Yuri S Genyk, Pere Gines, Patrick S Kamath, Sandra L Kane-Gill, Manish Kaushik, Nuttha Lumlertgul, Etienne Macedo, Rakhi Maiwall, Sebastian Marciano, Raimund H Pichler, Claudio Ronco, Puneeta Tandon, Juan-Carlos Q Velez, Ravindra L Mehta, François Durand

Faculty, Staff and Students Publications

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting …

Endovascular Management Of A Ruptured Aneurysm On A Posterior Inferior Cerebellar Artery With Extradural C2-Origin: Case Report And Literature Review, Rasmus Holmboe Dahl, Gary Lloyd Horn, Zeyad Metwalli, Shankar Prakash Gopinath, Goetz Benndorf

Faculty, Staff and Students Publications

Extracranial vascular pathology uncommonly causes intracranial subarachnoid hemorrhage (SAH). Among possible lesions are aneurysms at the craniocervical junction arising from a posterior inferior cerebellar artery (PICA) with an extradural origin. We describe a case of a 55-year-old female presenting with a sudden and severe headache. A computed tomography scan revealed a SAH within the fourth ventricle and cervical spinal canal, and a ruptured saccular aneurysm on a PICA with extradural C2-origin. Despite difficult access anatomy, endovascular treatment was feasible and resulted in subtotal initial occlusion and preservation of distal PICA flow. Upon 3-month follow-up, the aneurysm was completely occluded with …

Homozygous Missense Variants In Ykt6 Result In Loss Of Function And Are Associated With Developmental Delay, With Or Without Severe Infantile Liver Disease And Risk For Hepatocellular Carcinoma, Mengqi Ma, Mythily Ganapathi, Yiming Zheng, Kai-Li Tan, Oguz Kanca, Kevin E Bove, Norma Quintanilla, Sebnem O Sag, Sehime G Temel, Charles A Leduc, Amanda J Mcpartland, Elaine M Pereira, Yufeng Shen, Jacob Hagen, Christie P Thomas, Nhu Thao Nguyen Galván, Xueyang Pan, Shenzhao Lu, Jill A Rosenfeld, Daniel G Calame, Michael F Wangler, James R Lupski, Davut Pehlivan, Paula M Hertel, Wendy K Chung, Hugo J Bellen

Faculty, Staff and Students Publications

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.

METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6

RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, …

Genetic Deletion Of Galectin-3 Inhibits Pancreatic Cancer Progression And Enhances The Efficacy Of Immunotherapy, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a desmoplastic tumor stroma and immunosuppressive microenvironment. Galectin-3 (GAL3) is enriched in PDAC, highly expressed by cancer cells and myeloid cells. However, the functional roles of GAL3 in the PDAC microenvironment remain elusive.

Methods: We generated a novel transgenic mouse model (LSL-KrasG12D/+;Trp53loxP/loxP;Pdx1-Cre;Lgals3-/- [KPPC;Lgals3-/-]) that allows the genetic depletion of GAL3 from both cancer cells and myeloid cells in spontaneous PDAC formation. Single-cell RNA-sequencing analysis was used to identify the alterations in the tumor microenvironment upon GAL3 depletion. We investigated both the cancer cell-intrinsic function and immunosuppressive function of GAL3. We also evaluated …

Optimizing Sexual Reproductive Health Of Men And Women With Cystic Fibrosis: A Systematic Review, Anand G Iyer, Benjamin Yu, Amit Reddy, Mohit Khera

Faculty, Staff and Students Publications

This systematic review summarizes the impact of cystic fibrosis (CF) on sexual and reproductive health (SRH) in males and females, covering pubertal development, hormonal function, family planning, and fertility. Included articles featured historical CF diagnostic criteria, preclinical or clinical data (retrospective cohorts or open label trials), while excluded articles lacked full text availability, explicit methodology, or comparisons between CF and non-CF patients. Genotype differences in CFTR mutations influenced symptom severity. Males with CF experienced delayed puberty, hypogonadism, infertility from obstructive azoospermia, and semen parameter issues. Female CF patients showed decreased fertility, possibly linked to disrupted ionic balance and ovarian cystic …

Clinicopathologic Dissociation: Robust Lafora Body Accumulation In Malin Ko Mice Without Observable Changes In Home-Cage Behavior, Vaishnav Krishnan, Jun Wu, Arindam Ghosh Mazumder, Jessica L Kamen, Catharina Schirmer, Nandani Adhyapak, John Samuel Bass, Samuel C Lee, Atul Maheshwari, Gemma Molinaro, Jay R Gibson, Kimberly M Huber, Berge A Minassian

Faculty, Staff and Students Publications

Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age-dependent manner in all mouse models of LD. In this study, we applied home-cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin-deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6-7 …

Identification Of Immune-Associated Biomarkers Of Diabetes Nephropathy Tubulointerstitial Injury Based On Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis, Lin Wang, Jiaming Su, Zhongjie Liu, Shaowei Ding, Yaotan Li, Baoluo Hou, Yuxin Hu, Zhaoxi Dong, Jingyi Tang, Hongfang Liu, Weijing Liu

Faculty, Staff and Student Publications

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

METHODS: The …

Effects Of Vitamin D Supplementation On A Deep Learning-Based Mammographic Evaluation In Swog S0812, Julia E Mcguinness, Garnet L Anderson, Simukayi Mutasa, Dawn L Hershman, Mary Beth Terry, Parisa Tehranifar, Danika L Lew, Monica Yee, Eric A Brown, Sebastien S Kairouz, Nafisa Kuwajerwala, Therese B Bevers, John E Doster, Corrine Zarwan, Laura Kruper, Lori M Minasian, Leslie Ford, Banu Arun, Marian L Neuhouser, Gary E Goodman, Powel H Brown, Richard Ha, Katherine D Crew

Faculty, Staff and Student Publications

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was …

A Deep Catalogue Of Protein-Coding Variation In 983,578 Individuals, Kathie Y Sun, Xiaodong Bai, Siying Chen, Suying Bao, Chuanyi Zhang, Manav Kapoor, Joshua Backman, Tyler Joseph, Evan Maxwell, George Mitra, Alexander Gorovits, Adam Mansfield, Boris Boutkov, Sujit Gokhale, Lukas Habegger, Anthony Marcketta, Adam E Locke, Liron Ganel, Alicia Hawes, Michael D Kessler, Deepika Sharma, Jeffrey Staples, Jonas Bovijn, Sahar Gelfman, Alessandro Di Gioia, Veera M Rajagopal, Alexander Lopez, Jennifer Rico Varela, Jesús Alegre-Díaz, Jaime Berumen, Roberto Tapia-Conyer, Pablo Kuri-Morales, Jason Torres, Jonathan Emberson, Rory Collins, Regeneron Genetics Center, Rgc-Me Cohort Partners; Michael Cantor, Michael Cantor, Timothy Thornton, Hyun Min Kang, John D Overton, Alan R Shuldiner, M Laura Cremona, Mona Nafde, Aris Baras, Gonçalo Abecasis, Jonathan Marchini, Jeffrey G Reid, William Salerno, Suganthi Balasubramanian

Faculty, Staff and Student Publications

Rare coding variants that substantially affect function provide insights into the biology of a gene1-3. However, ascertaining the frequency of such variants requires large sample sizes4-8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of …

Targeting Of Cyp2e1 By Mirnas In Alcohol-Induced Intestine Injury, Hyejin Mun, Sungyul Lee, Suyoung Choi, Ji-Hoon Jeong, Seungbeom Ko, Yoo Lim Chun, Benjamin Deaton, Clay T Yeager, Audrey Boyette, Juliana Palmera, London Newman, Ping Zhou, Soona Shin, Dong-Chan Kim, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Jaeyul Kwon, Junyang Jung, Jeong Ho Chang, Je-Hyun Yoon

Faculty, Staff and Student Publications

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels. Although it is understood that EtOH promotes CYP2E1 induction and activation, the mechanisms that regulate CYP2E1 expression …

Ultrapotent Broadly Neutralizing Human-Llama Bispecific Antibodies Against Hiv-1, Jianliang Xu, Tongqing Zhou, Krisha Mckee, Baoshan Zhang, Cuiping Liu, Alexandra F Nazzari, Amarendra Pegu, Chen-Hsiang Shen, Jordan E Becker, Michael F Bender, Payton Chan, Anita Changela, Ridhi Chaudhary, Xuejun Chen, Tal Einav, Young Do Kwon, Bob C Lin, Mark K Louder, Jonah S Merriam, Nicholas C Morano, Sijy O'Dell, Adam S Olia, Reda Rawi, Ryan S Roark, Tyler Stephens, I-Ting Teng, Emily Tourtellott-Fogt, Shuishu Wang, Eun Sung Yang, Lawrence Shapiro, Yaroslav Tsybovsky, Nicole A Doria-Rose, Rafael Casellas, Peter D Kwong

Faculty, Staff and Student Publications

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM …

Effect Of Medicaid Expansion On Cancer Treatment And Survival Among Medicaid Beneficiaries And The Uninsured, Kristin M Primm, Hui Zhao, Naomi N Adjei, Charlotte C Sun, Alen Haas, Larissa A Meyer, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: The Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long-term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3-year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy.

METHODS: Medicaid-insured or uninsured patients aged 40-64 with stage I-III breast, cervical, colon, or non-small cell lung cancer within the National Cancer Database (NCDB). A difference-in-differences …

50-Nm Gas-Filled Protein Nanostructures To Enable The Access Of Lymphatic Cells By Ultrasound Technologies, Qionghua Shen, Zongru Li, Yixian Wang, Matthew D Meyer, Marc T De Guzman, Janie C Lim, Han Xiao, Richard R Bouchard, George J Lu

Faculty, Staff and Student Publications

Ultrasound imaging and ultrasound-mediated gene and drug delivery are rapidly advancing diagnostic and therapeutic methods; however, their use is often limited by the need for microbubbles, which cannot transverse many biological barriers due to their large size. Here, the authors introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles(GVs) that are referred to as

Ccr2+ Monocytes Promote White Matter Injury And Cognitive Dysfunction After Myocardial Infarction, Edward B Thorp, Mallory Filipp, Maria Dima, Chunfeng Tan, Matthew Feinstein, Brian Popko, Matthew Deberge

Faculty, Staff and Student Publications

Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells …

Emerging Cell And Molecular Targets For Treating Mucus Hypersecretion In Asthma, Ana M Jaramillo, Eszter K Vladar, Fernando Holguin, Burton F Dickey, Christopher M Evans

Faculty, Staff and Student Publications

Mucus provides a protective barrier that is crucial for host defense in the lungs. However, excessive or abnormal mucus can have pathophysiological consequences in many pulmonary diseases, including asthma. Patients with asthma are treated with agents that relax airway smooth muscle and reduce airway inflammation, but responses are often inadequate. In part, this is due to the inability of existing therapeutic agents to directly target mucus. Accordingly, there is a critical need to better understand how mucus hypersecretion and airway plugging are affected by the epithelial cells that synthesize, secrete, and transport mucus components. This review highlights recent advances in …

Corrigendum To "The Use Of Mr-Guided Radiation Therapy For Head And Neck Cancer And Recommended Reporting Guidance" Seminars In Radiation Oncology Volume 34 (2024) 69-83, Brigid A Mcdonald, Riccardo Dal Bello, Clifton D Fuller, Panagiotis Balermpas

Faculty, Staff and Student Publications

No abstract provided.

Epigenetic Regulation Of Heart Failure, Manisha Deogharia, Priyatansh Gurha

Faculty, Staff and Student Publications

Purpose of review: The studies on chromatin-modifying enzymes and how they respond to different stimuli within the cell have revolutionized our understanding of epigenetics. In this review, we provide an overview of the recent studies on epigenetic mechanisms implicated in heart failure.

Recent findings: We focus on the major mechanisms and the conceptual advances in epigenetics as evidenced by studies in humans and mouse models of heart failure. The significance of epigenetic modifications and the enzymes that catalyze them is also discussed. New findings from the studies of histone lysine demethylases demonstrate their significance in regulating fetal gene expression, as …

Pten Deficiency Induces An Extrahepatic Cholangitis-Cholangiocarcinoma Continuum Via Aurora Kinase A In Mice, Yan Yang, Jiale Wang, Jianhua Wan, Qianqian Cheng, Zenong Cheng, Xueli Zhou, Oliver Wang, Kelvin Shi, Lingxiang Wang, Bin Wang, Xiaohui Zhu, Jiaxiang Chen, Dongfeng Feng, Yang Liu, Yasmin Jahan-Mihan, Ashley N Haddock, Brandy H Edenfield, Guang Peng, Jessica D Hohenstein, Chantal E Mccabe, Daniel R O'Brien, Chen Wang, Sumera I Ilyas, Liuyan Jiang, Michael S Torbenson, Huamin Wang, Raouf E Nakhleh, Xuemei Shi, Ying Wang, Yan Bi, Gregory J Gores, Tushar Patel, Baoan Ji

Faculty, Staff and Student Publications

Background & aims: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease.

Methods: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the …

New Full-Counts Phase-Matched Data-Driven Gated (Ddg) Pet/Ct, Peng Sun, M Allan Thomas, Dershan Luo, Tinsu Pan

Faculty, Staff and Student Publications

Background: Data-driven gated (DDG) PET has gained clinical acceptance and has been shown to match or outperform external-device gated (EDG) PET. However, in most clinical applications, DDG PET is matched with helical CT acquired in free breathing (FB) at a random respiratory phase, leaving registration, and optimal attenuation correction (AC) to chance. Furthermore, DDG PET requires additional scan time to reduce image noise as it only preserves 35%-50% of the PET data at or near the end-expiratory phase of the breathing cycle.

Purpose: A new full-counts, phase-matched (FCPM) DDG PET/CT was developed based on a low-dose cine CT to improve …

Molecular Characterization Of Metastatic Oncocytoma With Exceptional Response To Treatment: A Case Report, Bradley R Webster, Christopher J Ricketts, Cathy D Vocke, Dionna Gamble, Daniel R Crooks, Ye Yang, Lindsay Friedman, Antoun Toubaji, Pavlos Msaouel, Jonathan M Hernandez, W Marston Linehan, Mark W Ball

Faculty, Staff and Student Publications

Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma.

Response-Adapted Ultra-Low-Dose 4 Gy Radiation As Definitive Therapy Of Gastric Malt Lymphoma: A Single-Centre, Pilot Trial, Jillian R Gunther, Jie Xu, Manoop S Bhutani, Paolo Strati, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Wenli Dong, Priya R Bhosale, Christopher R Flowers, Ranjit Nair, Luis Malpica Castillo, Luis Fayad, Swaminathan P Iyer, Simrit Parmer, Michael Wang, Hun Ju Lee, Felipe Samaniego, Jason Westin, Sairah Ahmed, Chijioke C Nze, Preetesh Jain, Sattva S Neelapu, Maria A Rodriguez, Dai Chihara, Loretta J Nastoupil, Chelsea C Pinnix

Faculty, Staff and Student Publications

Background: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach.

Methods: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total …

Identification Of A Clinically Efficacious Car T Cell Subset In Diffuse Large B Cell Lymphoma By Dynamic Multidimensional Single-Cell Profiling, Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa Martinez-Paniagua, Xingyue An, Irfan N Bandey, Melisa J Montalvo, Jay R T Adolacion, Arash Saeedi, Fatemeh Sadeghi, Kristen Fousek, Nahum Puebla-Osorio, Laurence J N Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, Sattva Neelapu, Navin Varadarajan

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8+ T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes. Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses …

Lacrimal Gland Adenocarcinoma Clinicopathologic Features And Outcomes Compared With Those Of Lacrimal Gland Adenoid Cystic Carcinoma, Hila Goldberg, Xinyang Jiang, Janet Fan, Jiawei Zhao, Jing Ning, Michelle Williams, Steven Frank, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC).

Methods: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed.

Results: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All …

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Sam Yuen, Tycel J Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R Flowers

Faculty, Staff and Student Publications

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months …

Hairy Cell Leukemia Variant And Who Classification Correspondence Re: 5th Edition Who Classification Haematolymphoid Tumors: Lymphoid Neoplasms, Michael Grever, Leslie Andritsos, Mirela Anghelina, Evgeny Arons, Versha Banerji, Jacqueline Barrientos, Seema A Bhat, James Blachly, Alessandro Broccoli, Timothy Call, Claire Dearden, Sascha Dietrich, Monica Else, Narendranath Epperla, Andrei Fagarasanu, Brunangelo Falini, Francesco Forconi, Alessandro Gozzetti, Paul Hampel, David J Hermel, Sunil Iyengar, James B Johnston, Gunnar Juliusson, Robert J Kreitman, Francesco Lauria, Gerard Lozanski, Christopher C Oakes, Sameer A Parikh, Jae Park, Graeme Quest, Kanti Rai, Farhad Ravandi, Tadeusz Robak, Kerry A Rogers, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine S Tam, Enrico Tiacci, Xavier Troussard, Bernhard Wörmann, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani

Faculty, Staff and Student Publications

No abstract provided.

Cone-Beam Ct With A Noncircular (Sine-On-Sphere) Orbit: Imaging Performance Of A Clinical System For Image-Guided Interventions, A Kyle Jones, Moiz Ahmad, Shaan M Raza, Stephen R Chen, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Purpose: We aim to compare the imaging performance of a cone-beam CT (CBCT) imaging system with noncircular scan protocols (sine-on-sphere) to a conventional circular orbit.

Approach: A biplane C-arm system (ARTIS Icono; Siemens Healthineers) capable of circular and noncircular CBCT acquisition was used, with the latter orbit (sine-on-sphere, "Sine Spin") executing a sinusoidal motion with ±10deg tilt amplitude over the half-scan orbit. A test phantom was used for the characterization of image uniformity, noise, noise-power spectrum (NPS), spatial resolution [modulation transfer function (MTF) in axial and oblique directions], and cone-beam artifacts. Findings were interpreted using an anthropomorphic head phantom with …

A Bayesian Latent-Subgroup Platform Design For Dose Optimization, Rongji Mu, Xiaojiang Zhan, Rui Sammi Tang, Ying Yuan

Faculty, Staff and Student Publications

The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At …

Delivery Of Hereditary Cancer Genetics Services To Patients Newly Diagnosed With Ovarian And Endometrial Cancers At Three Gynecologic Oncology Clinics In The Usa, Brazil, And Mexico, Erica M Bednar, Keiry A Paiz, Karen H Lu, Aline Patricia Soares Dias De Souza, Gabriela Oliveira, Carlos E Eduardo Mattos Da Cunha Andrade, Lenny Gallardo, Jairo Rubio-Cordero, David Cantu-De-León, Jose Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic.

Methods: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer …