Medical Specialties Commons^™

Considerations For Intensity Modulated Total Body Or Total Marrow And Lymphoid Irradiation, David Parsons, Tze Yee Lim, Jose R Teruel, Paulina Galavis, Stefano Agostinelli, Jieming Liang, Pietro Mancosu, Amanda Cherpak, Dennis N Stanley, Kang-Hyun Ahn, Bingqi Guo, Yesenia Gonzalez, Jay Burmeister, Jeffrey Y C Wong, Xuejun Gu, Grace Gwe-Ya Kim

Faculty, Staff and Student Publications

We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.

Circulating Micrornas And Cytokines As Prognostic Biomarkers For Doxorubicin-Induced Cardiac Injury And For Evaluating The Effectiveness Of An Exercise Intervention, Prince Jeyabal, Anchit Bhagat, Fei Wang, Michael Roth, J Andrew Livingston, Susan C Gilchrist, Jose Banchs, Michelle A T Hildebrandt, Joya Chandra, Anita Deswal, Efstratios Koutroumpakis, Jian Wang, Najat C Daw, Theresa A Honey, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Purpose: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.

Experimental design: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples …

Cell-Autonomous Effects Of Apoe4 In Restricting Microglial Response In Brain Homeostasis And Alzheimer’S Disease, Chia-Chen Liu, Na Wang, Yuanxin Chen, Yasuteru Inoue, Francis Shue, Yingxue Ren, Minghui Wang, Wenhui Qiao, Tadafumi C Ikezu, Zonghua Li, Jing Zhao, Yuka Martens, Sydney V Doss, Cassandra L Rosenberg, Suren Jeevaratnam, Lin Jia, Ana-Caroline Raulin, Fangfang Qi, Yiyang Zhu, Alla Alnobani, Joshua Knight, Yixing Chen, Cynthia Linares, Aishe Kurti, John D Fryer, Bin Zhang, Long-Jun Wu, Betty Y S Kim, Guojun Bu

Faculty, Staff and Student Publications

Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes …

Identification Of Novel Genetic Loci For Risk Of Multiple Myeloma By Functional Annotation, Angelica Macauda, Klara Briem, Alyssa Clay-Gilmour, Wendy Cozen, Asta Försti, Matteo Giaccherini, Chiara Corradi, Juan Sainz, Yasmeen Niazi, Rob Ter Horst, Yang Li, Mihai G Netea, Ulla Vogel, Kari Hemminki, Susan L Slager, Judit Varkonyi, Vibeke Andersen, Elzbieta Iskierka-Jazdzewska, Joaquin Mártinez-Lopez, Jan Zaucha, Nicola J Camp, S Vincent Rajkumar, Agnieszka Druzd-Sitek, Parveen Bhatti, Stephen J Chanock, Shaji K Kumar, Edyta Subocz, Grzegorz Mazur, Stefano Landi, Mitchell J Machiela, Andrés Jerez, Aaron D Norman, Michelle A T Hildebrandt, Katalin Kadar, Sonja I Berndt, Elad Ziv, Gabriele Buda, Arnon Nagler, Charles Dumontet, Malgorzata Raźny, Marzena Watek, Aleksandra Butrym, Norbert Grzasko, Marek Dudzinski, Malwina Rybicka-Ramos, Eva-Laure Matera, Ramón García-Sanz, Hartmut Goldschmidt, Krzysztof Jamroziak, Artur Jurczyszyn, Esther Clavero, Graham G Giles, Matteo Pelosini, Daria Zawirska, Marcin Kruszewski, Herlander Marques, Eva Haastrup, José Manuel Sánchez-Maldonado, Uta Bertsch, Marcin Rymko, Marc-Steffen Raab, Elizabeth E Brown, Jonathan N Hofmann, Celine Vachon, Daniele Campa, Federico Canzian

Faculty, Staff and Student Publications

No abstract provided.

Cost-Effectiveness Of [99mtc]Tilmanocept Relative To [99mtc]Sulfur Colloid For Sentinel Lymph Node Biopsy In Early Stage Oral Cavity Cancer, Karen Y Choi, Qiang Hao, Kathryn Carlisle, Christopher S Hollenbeak, Stephen Y Lai

Faculty, Staff and Student Publications

BACKGROUND: Several studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [99mTc]tilmanocept versus [99mTc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [99mTc]tilmanocept versus [99mTc]sulfur colloid in early stage OCSCC.

PATIENTS AND METHODS: A decision model of disease and treatment as a function of SLNB was created. Patients with …

Characteristics And Clinical Outcomes Of Patients With Myeloid Malignancies And Ddx41 Variants, Alex Bataller, Sanam Loghavi, Yoheved Gerstein, Alexandre Bazinet, Koji Sasaki, Kelly S Chien, Danielle Hammond, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas Short, Ghayas C Issa, Tapan M Kadia, Naval Daver, Guilin Tang, Andres Quesada, Keyur P Patel, Farhad Ravandi, Warren Fiskus, Cristopher P Mill, Hagop M Kantarjian, Kapil Bhalla, Guillermo Garcia-Manero, Betul Oran, Courtney D Dinardo

Faculty, Staff and Student Publications

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides …

Geographic Disparity Of Outcome In Patients With Cancer Over Decades: The Surveillance, Epidemiology, And End Results, Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C Issa, Sherry A Pierce, Kelly A Soltysiak, Martha S Tingen, Jorge E Cortes

Faculty, Staff and Student Publications

Background: Improvements in prevention, early detection, and effective cancer therapy have decreased cancer-related mortality; however, significant health disparities exist. Therefore, we investigated the impact of these disparities on survival.

Methods: In the Surveillance, Epidemiology, and End Results, we identified 784,341 patients with cancer between 1990 and 2016 in Georgia, 68,493 between 1990 and 1999; 371,353 between 2000 and 2009; and 322,932 between 2010 and 2016. We assessed the overall survival (OS) of patients with all cancers, chronic myeloid leukemia (CML), and lung cancer, given the dramatic improvement in outcomes in patients with CML since 2000 compared to the generally considerably …

Prevalence And Implications Of Significance Testing For Baseline Covariate Imbalance In Randomised Cancer Clinical Trials: The Table 1 Fallacy, Alexander D Sherry, Pavlos Msaouel, Zachary R Mccaw, Joseph Abi Jaoude, Eric J Hsu, Ramez Kouzy, Roshal Patel, Yumeng Yang, Timothy A Lin, Cullen M Taniguchi, Claus Rödel, Emmanouil Fokas, Chad Tang, Clifton David Fuller, Bruce Minsky, Tomer Meirson, Ryan Sun, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: The 'Table 1 Fallacy' refers to the unsound use of significance testing for comparing the distributions of baseline variables between randomised groups to draw erroneous conclusions about balance or imbalance. We performed a cross-sectional study of the Table 1 Fallacy in phase III oncology trials.

Methods: From ClinicalTrials.gov, 1877 randomised trials were screened. Multivariable logistic regressions evaluated predictors of the Table 1 Fallacy.

Results: A total of 765 randomised controlled trials involving 553,405 patients were analysed. The Table 1 Fallacy was observed in 25% of trials (188 of 765), with 3% of comparisons deemed significant (59 of 2353), approximating …

Development And Implementation Of Optimized Endogenous Contrast Sequences For Delineation In Adaptive Radiotherapy On A 15t Mr-Linear-Accelerator: A Prospective R-Ideal Stage 0–2a Quantitative/Qualitative Evaluation Of In Vivo Site-Specific Quality-Assurance Using A 3d T2 Fat-Suppressed Platform For Head And Neck Cancer, Travis C Salzillo, M Alex Dresner, Ashley Way, Kareem A Wahid, Brigid A Mcdonald, Sam Mulder, Mohamed A Naser, Renjie He, Yao Ding, Alison Yoder, Sara Ahmed, Kelsey L Corrigan, Gohar S Manzar, Lauren Andring, Chelsea Pinnix, R Jason Stafford, Abdallah S R Mohamed, John Christodouleas, Jihong Wang, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: To improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T hybrid magnetic resonance imaging/linear accelerator (MR-Linac), three-dimensional (3D), T2-weighted, fat-suppressed magnetic resonance imaging sequences were developed and optimized.

Approach: After initial testing, spectral attenuated inversion recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a nonsuppressed, T2-weighted sequence were acquired for five HNC patients using a 1.5T MR-Linac. MR physicists identified persistent artifacts in two of the SPAIR sequences, so the remaining three SPAIR sequences were further analyzed. The gross primary tumor volume, metastatic lymph nodes, parotid glands, …

Tolerability And Efficacy Of The Anticluster Of Differentiation 47 Antibody Magrolimab Combined With Azacitidine In Patients With Previously Untreated Aml: Phase Ib Results, Naval G Daver, Paresh Vyas, Suman Kambhampati, Monzr M Al Malki, Richard A Larson, Adam S Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N Tanaka, Terrence J Bradley, Deepa Jeyakumar, Eunice S Wang, Kendra Sweet, Hagop M Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F Zeidner, David A Sallman

Faculty, Staff and Student Publications

Purpose: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every …

Patient-Reported Quality Of Life After Breast-Conserving Surgery With Radiotherapy Versus Mastectomy And Reconstruction, Kevin Diao, Xiudong Lei, Weiguo He, Reshma Jagsi, Sharon H Giordano, Grace L Smith, Abigail Caudle, Yu Shen, Susan K Peterson, Benjamin D Smith

Faculty, Staff and Student Publications

Objective: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors.

Background: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood.

Methods: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. …

High-Dose Chemotherapy And Autologous Stem Cell Transplantation For Relapsed Or Refractory Primary Mediastinal Large B-Cell Lymphoma, Hanan Alkhaldi, Alec Reinhardt, Melissa Barnett, Suprateek Kundu, Chitra Hosing, Jeremy Ramdial, Neeraj Saini, Samer Srour, Amin Alousi, Partow Kebriaei, Uday Popat, Muzaffar Qazilbash, Richard Champlin, Elizabeth J Shpall, Allison Gulbis, Terri Lynn Shigle, Bouthaina Dabaja, Chelsea Pinnix, Sairah Ahmed, Raphael Steiner, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy with or without radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC), with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. The 60 study patients received either rituximab-BEAM (n = 37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) with or without vorinostat (n = 23), followed by ASCT. Forty-six patients received mediastinal RT, …

Exosomes Modified With Anti-Mek1 Sirna Lead To An Effective Silencing Of Triple Negative Breast Cancer Cells, Débora Ferreira, Cátia Santos-Pereira, Marta Costa, Julieta Afonso, Sujuan Yang, Janine Hensel, Kathleen M Mcandrews, Adhemar Longatto-Filho, Rui Fernandes, Joana B Melo, Fátima Baltazar, João N Moreira, Raghu Kalluri, Ligia R Rodrigues

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an …

Engineering A Tunable Micropattern-Array Assay To Sort Single Extracellular Vesicles And Particles To Detect Rna And Protein In Situ, Jingjing Zhang, Xilal Y Rima, Xinyu Wang, Luong T H Nguyen, Kristin Huntoon, Yifan Ma, Paola Loreto Palacio, Kim Truc Nguyen, Karunya Albert, Minh-Dao Duong-Thi, Nicole Walters, Kwang Joo Kwak, Min Jin Yoon, Hong Li, Jacob Doon-Ralls, Colin L Hisey, Daeyong Lee, Yifan Wang, Jonghoon Ha, Kelsey Scherler, Shannon Fallen, Inyoul Lee, Andre F Palmer, Wen Jiang, Setty M Magaña, Kai Wang, Betty Y S Kim, L James Lee, Eduardo Reátegui

Faculty, Staff and Student Publications

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVPPRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVPPRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVPPRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex …

Adavosertib Enhances Antitumor Activity Of Trastuzumab Deruxtecan In Her2-Expressing Cancers, Timothy P Diperi, Kurt W Evans, Maria Gabriela Raso, Ming Zhao, Yasmeen Q Rizvi, Xiaofeng Zheng, Bailiang Wang, Bryce P Kirby, Kathleen Kong, Michael Kahle, Timothy A Yap, Ecaterina E Dumbrava, Jaffer A Ajani, Siqing Fu, Khandan Keyomarsi, Funda Meric-Bernstam

Faculty, Staff and Student Publications

PURPOSE: Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, a Wee1 kinase inhibitor, and a mechanism of resistance to HER2-targeted therapy.

EXPERIMENTAL DESIGN: Copy number and genomic sequencing data from The Cancer Genome Atlas and MD Anderson Cancer Center databases were analyzed to assess ERBB2 and CCNE1 expression. Molecular characteristics of tumors and patient-derived xenografts (PDX) were assessed by next-generation sequencing, whole-exome sequencing, fluorescent in situ hybridization, and IHC. In vitro, CCNE1 was overexpressed or knocked down in HER2+ cell lines to evaluate drug combination efficacy. In vivo, NSG mice bearing PDXs were subjected to …

Benefits Of The Enhanced Recovery After Surgery (Eras) Pathway With Quadratus Lumborum Blocks For Minimally Invasive Gynecologic Surgery Patients: A Retrospective Cohort Study, Paul S Lee, Laurie L Brunette, Intira Sriprasert, Mohamed Eloustaz, Rasika Deshpande, Crystal Adams, Laila Muderspach, Lynda Roman, Shane Dickerson, Michael P Kim

Faculty, Staff and Student Publications

STUDY OBJECTIVE: This study aimed to determine the effect of the implementation of the Enhanced Recovery After Surgery (ERAS) protocol among patients receiving minimally invasive gynecologic surgery.

DESIGN AND SETTING: This retrospective cohort study was performed in a tertiary care hospital.

PATIENTS: A total of 328 females who underwent minimally invasive gynecologic surgeries requiring at least one overnight stay at Keck Hospital of University of Southern California (USC), California, USA, from 2016 to 2020 were included in this study.

INTERVENTIONS: The institutional ERAS protocol was implemented in late 2018. A total of 186 patients from 2016 to 2018 prior to …

Oritavancin Vs Standard Of Care For Treatment Of Nonendovascular Gram-Positive Bloodstream Infections, Ryan P Moenster, Ashleigh Wallace-Lacey, Hannah Western, Seth Tiefenaur, Anosha Abdulbasir, Justin Alberts, Jonathan Doty, Hartley Abner, Danielle Skouby, Michael Lorenz, Rebecca Fong, Jyoti Arora, Travis W Linneman

Faculty, Staff and Student Publications

BACKGROUND: Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI).

METHODS: This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once …

Inflammatory Activity Of Epithelial Stem Cell Variants From Cystic Fibrosis Lungs Is Not Resolved By Cftr Modulators, Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L Metersky, Matthew Vincent, Christopher P Crum, Richard C Boucher, Harry Karmouty-Quintana, Howard J Huang, Ajay Sheshadri, Burton F Dickey, Kalpaj R Parekh, John F Engelhardt, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Rationale

CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs.

Objectives

To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) …

Care After Premenopausal Risk-Reducing Salpingo-Oophorectomy In High-Risk Women: Scoping Review And International Consensus Recommendations, Denise R Nebgen, Susan M Domchek, Joanne Kotsopoulos, Joanne A De Hullu, Emma J Crosbie, Vincent Singh Paramanandam, Monique M A Brood-Van Zanten, Barbara M Norquist, Theresa Guise, Serge Rozenberg, Allison W Kurian, Holly J Pederson, Nese Yuksel, Rachel Michaelson-Cohen, Sharon L Bober, Agnaldo Lopes Da Silva Filho, Nora Johansen, F Guidozzi, D Gareth Evans, Usha Menon, Sheryl A Kingsberg, C Bethan Powell, Giovanni Grandi, Claudia Marchetti, Michelle Jacobson, Donal J Brennan, Martha Hickey

Faculty, Staff and Student Publications

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Comparison Of Progression-Free Survival Outcome Of Sentinel Node Biopsy Without Ultrastaging Versus Lymphadenectomy In Endometrial Cancer: A Propensity-Matched Analysis, Dahye Lee, Yoo-Na Kim, Sang Hyun Cho, Hye Soo Yoon, Young Tae Kim, Sunghoon Kim, Sang Wun Kim

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND).

METHODS: Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 - 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progression-free survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed.

RESULTS: After excluding …

Improved Humoral Immunity And Protection Against Influenza Virus Infection With A 3d Porous Biomaterial Vaccine, Hiromi Miwa, Olivia Q Antao, Kindra M Kelly-Scumpia, Sevana Baghdasarian, Daniel P Mayer, Lily Shang, Gina M Sanchez, Maani M Archang, Philip O Scumpia, Jason S Weinstein, Dino Di Carlo

Faculty, Staff and Student Publications

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Mary U Feng, Kristy K Brock, Randi Kudner, Peter Balter, Jeffrey C Buchsbaum, Amanda Caissie, Elizabeth Covington, Emily C Daugherty, Andre L Dekker, Clifton D Fuller, Anneka L Hallstrom, David S Hong, Julian C Hong, Sophia C Kamran, Eva Katsoulakis, John Kildea, Andra V Krauze, Jon J Kruse, Tod Mcnutt, Michelle Mierzwa, Amy Moreno, Jatinder R Palta, Richard Popple, Thomas G Purdie, Susan Richardson, Gregory C Sharp, Shiraishi Satomi, Lawrence R Tarbox, Aradhana M Venkatesan, Alon Witztum, Kelly E Woods, Yuan Yao, Keyvan Farahani, Sanjay Aneja, Peter E Gabriel, Lubomire Hadjiiski, Dan Ruan, Jeffrey H Siewerdsen, Steven Bratt, Michelle Casagni, Su Chen, John C Christodouleas, Anthony Didonato, James Hayman, Rishhab Kapoor, Saul Kravitz, Sharon Sebastian, Martin Von Siebenthal, Walter Bosch, Coen Hurkmans, Sue S Yom, Ying Xiao

Faculty, Staff and Student Publications

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …

Primary Tumor Site For Localized Merkel Cell Carcinoma Drives Different Management Strategies Without Impacting Oncologic Outcomes, Samuel Cass, Brandon Cope, Andrew J Bishop, Yi-Ju Chiang, B Ashleigh Guadagnolo, Ahsan Farooqi, William Morrison, Russell G Witt, Riyad N H Seervai, Adam S Garden, Clifton D Fuller, Ryan P Goepfert, Merrick Ross, Jeffrey E Gershenwald, Michael Wong, Phyu P Aung, Emily Z Keung, Devarati Mitra

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Clinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era.

MATERIALS AND METHODS: Patterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014-2021.

RESULTS: Of 80 patients who met inclusion criteria, the primary tumor anatomic site was head …

Systematic Review Of Genetic Polymorphisms Associated With Acute Pain Induced By Radiotherapy For Head And Neck Cancers, Vivian Salama, Yimin Geng, Jillian Rigert, Clifton D Fuller, Sanjay Shete, Amy C Moreno

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVE: Pain is the most common acute symptom following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of RT-induced pain makes it highly challenging to manage. Multiple studies were conducted to identify genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this review, we summarize the potential mechanisms of acute pain after RT in HNC and identify genetic variants associated with RT-induced acute pain and relevant acute toxicities.

METHODS: A comprehensive search of Ovid Medline, EMBASE and Web of Science databases using terms including "Variants", "Polymorphisms", "Radiotherapy", "Acute pain", …

Opioid-Free Discharge After Pancreatic Resection Through A Learning Health System Paradigm, Artem Boyev, Anish J Jain, Timothy E Newhook, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Elsa M Arvide, Whitney L Dewhurst, Michael P Kim, Jessica E Maxwell, Naruhiko Ikoma, Rebecca A Snyder, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume.

Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes.

Design, setting, and participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = …

Supportive Care For Dual Caregivers Who Care For Their Partner With Cancer And Their Young Children, Sujin Ann-Yi, Kathrin Milbury, Morgan Jones, Victoria Necroto, Meagan Whisenant, Yisheng Li, Eduardo Bruera

Faculty, Staff and Student Publications

Purpose: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program.

Methods: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological …

Engineering Cannabidiol Synergistic Carbon Monoxide Nanocomplexes To Enhance Cancer Therapy Via Excessive Autophagy, Chang Xiao, Yue Sun, Jialong Fan, William Nguyen, Simin Chen, Ying Long, Wei Chen, Aiguo Zhu, Bin Liu

Faculty, Staff and Student Publications

Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The comprehensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, …

Model-Informed Drug Development Of Autologous Car-T Cell Therapy: Strategies To Optimize Car-T Cell Exposure Leveraging Cell Kinetic/Dynamic Modeling, Anna M Mc Laughlin, Peter A Milligan, Cassian Yee, Martin Bergstrand

Faculty, Staff and Student Publications

Autologous Chimeric antigen receptor (CAR-T) cell therapy has been highly successful in the treatment of aggressive hematological malignancies and is also being evaluated for the treatment of solid tumors as well as other therapeutic areas. A challenge, however, is that up to 60% of patients do not sustain a long-term response. Low CAR-T cell exposure has been suggested as an underlying factor for a poor prognosis. CAR-T cell therapy is a novel therapeutic modality with unique kinetic and dynamic properties. Importantly, "clear" dose-exposure relationships do not seem to exist for any of the currently approved CAR-T cell products. In other …

Style Transfer-Assisted Deep Learning Method For Kidney Segmentation At Multiphase Mri, Junyu Guo, Manu Goyal, Yin Xi, Lauren Hinojosa, Gaelle Haddad, Emin Albayrak, Ivan Pedrosa

Faculty, Staff and Student Publications

Purpose: To develop and validate a semisupervised style transfer-assisted deep learning method for automated segmentation of the kidneys using multiphase contrast-enhanced (MCE) MRI acquisitions.

Materials and methods: This retrospective, Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study included 125 patients (mean age, 57.3 years; 67 male, 58 female) with renal masses. Cohort 1 consisted of 102 coronal T2-weighted MRI acquisitions and 27 MCE MRI acquisitions during the corticomedullary phase. Cohort 2 comprised 92 MCE MRI acquisitions (23 acquisitions during four phases each, including precontrast, corticomedullary, early nephrographic, and nephrographic phases). The kidneys were manually segmented on T2-weighted images. …

Human Intestinal Organoids From Cronkhite-Canada Syndrome Patients Reveal Link Between Serotonin And Proliferation, Victoria Poplaski, Carolyn Bomidi, Amal Kambal, Hoa Nguyen-Phuc, Sara C Di Rienzi, Heather A Danhof, Xi-Lei Zeng, Linda A Feagins, Nan Deng, Eduardo Vilar, Florencia Mcallister, Cristian Coarfa, Soyoun Min, Hyun Jung Kim, Richa Shukla, Robert Britton, Mary K Estes, Sarah E Blutt

Faculty, Staff and Student Publications

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation …