Medicine and Health Sciences Commons^™

Polygenic Score For Clinicopathologic Features And Survival Outcomes In Papillary Thyroid Carcinoma, Sophie Li, Guibin Zheng, Li Xu, Maitrayee Goswami, Mark E Zafereo, Steven I Sherman, Guojun Li, Erich M Sturgis, Jennifer R Wang

Faculty, Staff and Students Publications

Importance: Genome-wide association studies have identified germline variants associated with the development of papillary thyroid carcinoma (PTC) that can be used to construct a polygenic score (PGS). It is important to determine whether patients with higher germline genetic risk, as summarized using PGS, present with more aggressive disease and/or develop worse clinical outcomes.

Objective: To assess whether germline risk defined by PGS is associated with clinicopathologic features and survival outcomes for patients with PTC.

Design, setting, and participants: This retrospective cohort study included patients with newly diagnosed PTC who presented to The University of Texas MD Anderson Cancer Center for …

Disease Activity Of Rheumatoid Arthritis And Kidney Function Decline: A Large Prospective Registry Study, Sho Fukui, Wolfgang C Winkelmayer, Sara K Tedeschi, Javier Marrugo, Hongshu Guan, Leslie Harrold, Heather J Litman, Tomohiro Shinozaki, Daniel H Solomon

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is a common comorbidity of rheumatoid arthritis (RA). The association of longitudinal RA disease activity with long-term kidney function has remained uncertain.

Method: We analysed a multicentre prospective RA registry in the USA from 2001 to 2022. The exposure was updated time-averaged Clinical Disease Activity Index (TA-CDAI) categories from study enrolment. The primary outcome was a longitudinal estimated glomerular filtration rate (eGFR) change. Secondary outcomes included developments of CKD stage G3a (eGFR< 60 mL/min/1.73 m2) and stage G3b (eGFR< 45 mL/min/1.73 m2). Results were adjusted for relevant time-fixed and time-varying covariates.

Results: 31 129 patients (median age: 58.0 years, female: 76.3%, median eGFR: 90.7 mL/min/1.73 m2) contributed 234 973 visits and 146 778 person-years …

Intercostal Nerve Cryoablation In Lung Transplantation: A Single-Center, Propensity Score-Matched Analysis, Marcelo Salan-Gomez, Ramiro Fernandez, Ethan D'Silva, Belia Camarena, Emma Hills, Andres Leon, Syed B Peer, Abdussalam Elsenousi, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Background: Achieving adequate pain control after lung transplantation is an essential milestone in a patient's recovery. We compared postoperative opioid use, clinical outcomes, and respiratory function in lung transplant recipients treated with intercostal nerve cryoablation (INC) compared to those receiving standard pain management.

Methods: We reviewed all adult lung transplants performed at our center between January 2016 and December 2022. We excluded cases performed through median sternotomy and patients with prior thoracotomies, multiorgan transplants, and redo transplants. We performed a propensity score-matched analysis, comparing patients who received INC versus those who received standard pain management. The primary outcome was cumulative …

Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the …

Unprecedented Female Mutation Bias In The Aye-Aye, A Highly Unusual Lemur From Madagascar, Richard J Wang, Yadira Peña-García, Muthuswamy Raveendran, R Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D Yoder, Joe H Simmons, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality-without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to …

Historical Demography And Species Distribution Models Shed Light On Speciation In Primates Of Northeast India, Mihir Trivedi, Kunal Arekar, Shivakumara Manu, Lukas F K Kuderna, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet, Govindhaswamy Umapathy

Faculty, Staff and Students Publications

Past climate change is one of the important factors influencing primate speciation. Populations of various species could have risen or declined in response to these climatic fluctuations. Northeast India harbors a rich diversity of primates, where such fluctuations can be implicated. Recent advances in climate modeling as well as genomic data analysis has paved the way for understanding how species accumulate at a particular geographic region. We utilized these methods to explore the primate diversity in this unique region in relation to past climate change. To ascertain the population level changes, we inferred the demographic history of nine species of …

Sustainable Solutions To The Continuous Threat Of Antimicrobial Resistance, Brad Spellberg, David N Gilbert, Michael Baym, Gonzalo Bearman, Tom Boyles, Arturo Casadevall, Graeme N Forrest, Sarah Freling, Bassam Ghanem, Fergus Hamilton, Brian Luna, Jessica Moore, Daniel M Musher, Travis B Nielsen, Priya Nori, Matthew C Phillips, Liise-Anne Pirofski, Andrew F Shorr, Steven Y C Tong, Todd C Lee, Emily G Mcdonald

Faculty, Staff and Students Publications

To combat antimicrobial resistance (AMR), advocates have called for passage of the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act in the United States, which would appropriate $6 billion in new taxpayer-funded subsidies for antibiotic development. However, the number of antibiotics in clinical development, and US Food and Drug Administration approvals of new antibiotics, have already markedly increased in the last 15 years. Thus, instead of focusing on more economic subsidies, we recommend reducing selective pressure driving AMR by (1) establishing pay-for-performance mechanisms that disincentivize overprescribing of antibiotics, (2) focusing existing research and development funding on strategies that decrease …

Inflammatory Hyperplastic Mass Mimicking Local Recurrence Following Endoscopic Submucosal Dissection Of A Colonic Adenoma, Isiah Gonzalez, Linda K Green, Salmaan Jawaid, Wasseem Skef

Faculty, Staff and Students Publications

This case presents a hyperplastic inflammatory mass at the resection site of a colorectal tubular adenoma. A 65-year-old man with a history of alcohol-associated liver cirrhosis, >10 lifetime polyps, and a CHEK2 mutation underwent hybrid endoscopic submucosal dissection of a 3 cm lateral spreading tumor, nongranular, Paris 0-IIa polyp in the ascending colon. Postresection pathology confirmed tubular adenoma with negative margins (R0). Six-month surveillance colonoscopy in the community identified a mass at the resection site, initially suspected to be local recurrence. Repeat colonoscopy demonstrated a mass which appeared inflammatory, with a Kudo type II hyperplastic pit pattern on narrow-band imaging …

Minimal Clinically Important Difference In Obsessive-Compulsive Disorder, Matti Cervin, Eric A Storch, Lara Farrell, Erik Andersson, Christian Rück, Daniel A Geller, David Mataix-Cols

Faculty, Staff and Students Publications

No abstract provided.

Reperfused Myocardial Infarction: The Road To Ccs Classification Of Acute Mi And Beyond., Rohan Dharmakumar, Robert A Kloner, Michael Fishbein, Gerd Heusch, Keyur P Vora, Robert Gropler, Timothy Henry, Fai Shing-Chan, Dhirendra Singh, Nithya Jambunathan, Ramesh Subramanian, Rolf P Kreutz, Grant W Reed, Richard J Kovacs, Edward Fry, Ankur Kalra, Andreas Kumar, Subha V Raman

Heart and Vascular Articles

The Canadian Cardiovascular Society recently put forth a new classification of acute reperfused myocardial infarction (MI) based on stages of myocardial injury. Backed by more than 5 decades of intense investigation in the field, the key message of this new classification is that not all MIs are the same and that the type and extent of myocardial injury should be considered in diagnosing and treating MI. We review the literature with the goal of highlighting the progressive advances that enabled the synthesis of the Canadian Cardiovascular Society classification into 4 distinct stages of tissue injury. We emphasize the major breakthroughs …

Forearm Versus Upper Arm Location Of Arteriovenous Access Used At Hemodialysis Initiation: Temporal Trends And Racial Disparities, Melandrea L Worsley, Jingbo Niu, Kevin F Erickson, Neal R Barshes, Wolfgang C Winkelmayer, L Parker Gregg

Faculty, Staff and Students Publications

Rationale & objective: Race and ethnicity differences exist in the type of arteriovenous access (AVA, including fistulas and grafts) used at hemodialysis (HD) initiation. The preferred anatomic location for the creation of an initial HD AVA is typically in the forearm We evaluated race and ethnicity differences in the use of an AVA in the forearm location at HD initiation.

Study design: Retrospective cohort study.

Setting & participants: Using records from DaVita Kidney Care linked to the US Renal Data System (USRDS), we evaluated patients aged≥16 years who initiated in-center HD with an AVA between 2006 and 2019.

Predictor: Race …

Qm107, A Novel Cd148 (Rtp Type J) Activating Peptide Therapy For Treating Neovascular Age-Related Macular Degeneration, Samantha Arokiasamy, Michaela J M Balderstone, Faheem Shaik, Enrico Cristante, Thomas C Moseley, Akshay Madoo, Matteo Rizzi, James W Bainbridge, Konstantin Tsoyi, Ivan O Rosas, James R Whiteford, Giulia De Rossi

Faculty, Staff and Students Publications

Background and purpose: Angiogenesis is a pathological component of neovascular age-related macular degeneration. Current therapies, although successful, are prone to high levels of patient non-response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan-2 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age-related macular degeneration.

Experimental approach: We tested a peptide (QM107) derived from syndecan-2 in a variety of angiogenesis models and …

American Cochlear Implant Alliance Position Statement On Newborn Congenital Cytomegalovirus Screening, Megan Honor Pesch, Kevin David Brown, Amy L Birath, Gail J Demmler-Harrison, Cailtin Sapp, Anne Morgan Selleck, Alex D Sweeney

Faculty, Staff and Students Publications

It is estimated that 1 in every 200 US newborns has congenital cytomegalovirus (cCMV). Delayed identification of cCMV in newborns precludes timely intervention to mitigate sequelae of the infection such as hearing loss and other neurological complications. Newborn testing for cCMV enables appropriate diagnosis and intervention by multidisciplinary teams to properly manage the immediate sequelae of cCMV, avoid unnecessary additional testing that can result from delayed diagnosis, and monitor for future complications. It is the position of the American Cochlear Implant Alliance, the National CMV Foundation, and the American Academy of Otolaryngology-Head and Neck Surgery that universal newborn cCMV screening …

Decoding Cancer Etiology With Cellular Reprogramming, Mo-Fan Huang, Megan E Fisher, Trinh T T Phan, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

Cancer research remains clinically unmet in many areas due to limited access to patient samples and the lack of reliable model systems that truly reflect human cancer biology. The emergence of patient-derived induced pluripotent stem cells and engineered human pluripotent stem cells (hPSCs) has helped overcome these challenges, offering a versatile alternative platform for advancing cancer research. These hPSCs are already proving to be valuable models for studying specific cancer driver mutations, offering insights into cancer origins, pathogenesis, tumor heterogeneity, clonal evolution, and facilitating drug discovery and testing. This article reviews recent progress in utilizing hPSCs for clinically relevant cancer …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

Imaging Lung Tumor Motion Using Integrated-Mode Proton Radiography-A Phantom Study Towards Tumor Tracking In Proton Radiotherapy, Ryan Fullarton, Mikaël Simard, Lennart Volz, Allison Toltz, Savanna Chung, Christoph Schuy, Daniel G Robertson, Gary Royle, Sam Beddar, Colin Baker, Christian Graeff, Charles-Antoine Collins-Fekete

Faculty, Staff and Student Publications

BACKGROUND: Motion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.

PURPOSE: Proton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated-mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring …

Open-Chest Cardiac Ultrasound-Mediated Imaging With A Vacuum Coupler, Nilesh Mathuria, Krithik Vishwanath, Giorgio Brero, Blake C Fallon, Antonio Martino, Richard C Willson, Carly S Filgueira, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods.

PURPOSE: To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches.

METHODS: The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the …

Performance Comparison Of 10 State-Of-The-Art Machine Learning Algorithms For Outcome Prediction Modeling Of Radiation-Induced Toxicity, Ramon M Salazar, Saurabh S Nair, Alexandra O Leone, Ting Xu, Raymond P Mumme, Jack D Duryea, Brian De, Kelsey L Corrigan, Michael K Rooney, Matthew S Ning, Prajnan Das, Emma B Holliday, Zhongxing Liao, Laurence E Court, Joshua S Niedzielski

Faculty, Staff and Student Publications

Purpose: To evaluate the efficacy of prominent machine learning algorithms in predicting normal tissue complication probability using clinical data obtained from 2 distinct disease sites and to create a software tool that facilitates the automatic determination of the optimal algorithm to model any given labeled data set.

Methods and materials: We obtained 3 sets of radiation toxicity data (478 patients) from our clinic: gastrointestinal toxicity, radiation pneumonitis, and radiation esophagitis. These data comprised clinicopathological and dosimetric information for patients diagnosed with non-small cell lung cancer and anal squamous cell carcinoma. Each data set was modeled using 11 commonly employed machine …

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

Real-World Neoadjuvant And Adjuvant Trastuzumab-Containing Regimen Patterns And Their Association With Survival Among Patients With Operable Her2-Positive Breast Cancer From 2007 To 2021, Hui Zhao, Chan Shen, Jaime J Laureano, Xiudong Lei, Jiangong Niu, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Chemotherapy in combination with trastuzumab is the standard neoadjuvant and adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Assessing the regimens administered to patients with HER2-positive BC in the real world is lacking. We evaluated neoadjuvant and adjuvant regimen patterns among HER2-positive BC patients (2007 to 2021) identified in a health insurance claims database.

Methods: Female BC patients ≥ 18 years who received chemotherapy, surgery, and trastuzumab were chosen from Optum's de-identified Clinformatics® Data Mart database. Summary statistics, Joinpoint models, Kaplan-Meier survival curves, and Cox regression models were used to analyze the data.

Results: …

Molecular Profiling Of Bladder Cancer Xenografts Defines Relevant Molecular Subtypes And Provides A Resource For Biomarker Discovery, Sharada Mokkapati, Ganiraju Manyam, Alexis R Steinmetz, Côme Tholomier, Alberto Martini, Woonyoung Choi, Bogdon Czerniak, Byron H Lee, Colin P Dinney, David J Mcconkey

Faculty, Staff and Student Publications

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal …

Status Of Abortion Curriculum In Genetic Counseling: Survey Of Graduate Programs And Recent Graduates In The United States, Gina Sanchez, S Shahrukh Hashmi, Erica Bednar, Sarah Horvath, Bhavik Kumar, Katelynn Sagaser, Claire N Singletary, Aarti Ramdaney

Faculty, Staff and Student Publications

Genetic counselors (GCs) are trained to help individuals navigate the medical and psychological implications of genetic test results, familial conditions, and ultrasound anomalies. Therefore, familiarity with reproductive options, including abortion, is vital. However, previous studies have found gaps in GCs' knowledge regarding abortion care and there are currently no recommendations regarding abortion curriculum. This study aimed to assess the state of abortion curriculum in genetic counseling graduate programs in the United States and to examine and compare the satisfaction levels of program representatives and recent graduates. Program representatives and recent graduates were invited to complete an anonymous survey evaluating the …

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …

Forecasting Intraoperative Hypotension During Hepatobiliary Surgery, Juan P Cata, Bhavin Soni, Shreyas Bhavsar, Parvathy Sudhir Pillai, Tatiana A Rypinski, Anshuj Deva, Jeffrey H Siewerdsen, Jose M Soliz

Faculty, Staff and Student Publications

Prediction and avoidance of intraoperative hypotension (IOH) can lead to less postoperative morbidity. Machine learning (ML) is increasingly being applied to predict IOH. We hypothesize that incorporating demographic and physiological features in an ML model will improve the performance of IOH prediction. In addition, we added a "dial" feature to alter prediction performance. An ML prediction model was built based on a multivariate random forest (RF) trained algorithm using 13 physiologic time series and patient demographic data (age, sex, and BMI) for adult patients undergoing hepatobiliary surgery. A novel implementation was developed with an adjustable, multi-model voting (MMV) approach to …

Durable Remission After Targeted Therapy In Braf V600e–Mutant Metastatic Colorectal Cancer: Case Report, Daniel A Fox, Deepak Bhamidipati, Scott Kopetz, David S Hong

Faculty, Staff and Student Publications

BRAF mutation leads to constitutive activation of the MAPK pathway and is associated with the immune-activating molecular subtype of colorectal cancer. Targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (CRC) has significantly improved outcomes for these patients when combined with anti–epithelial growth factor receptor (EGFR) therapy. However, most patients ultimately develop disease progression. We report a case of a patient with metastatic-deficient mismatch repair, BRAF V600E–mutated CRC, who achieved a durable complete response to vemurafenib plus cetuximab and chemotherapy despite initial high burden of disease, including peritoneal involvement. Recent clinical trials of combined anti-EGFR/anti–BRAF V600E therapy in …

A Phase Ib Trial Of Selinexor In Combination With Immune Checkpoint Blockade In Patients With Advanced Renal Cell Carcinoma, Omar Alhalabi, Mohamed A Gouda, Denái R Milton, Hassan Ahmed Momin, Bulent Yilmaz, Bettzy Stephen, Chinenye Lynette Ejezie, Justin Tyler Moyers, Serdar A Gurses, Jeffrey How, Siqing Fu, Jordi Rodon, David S Hong, Sarina A Piha-Paul, Vivek Subbiah, Ecaterina Elena Dumbrava, Daniel D Karp, Filip Janku, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.

Methods: NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL + NIVO and SEL …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Hsp90: Bringing It All Together, Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Faculty, Staff and Student Publications

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs most other machines in the cell in sophistication. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …