Medicine and Health Sciences Commons^™

Serial Cytoreductive Surgery And Survival Outcomes In Recurrent Adult-Type Ovarian Granulosa Cell Tumors, Jeffrey A How, Alejandra Flores Legarreta, Katelyn F Handley, Bryan Fellman, Katherine I Foster, Deanna Glassman, Veena K Vuttaradhi, Allison L Brodsky, Barrett Lawson, Michael Frumovitz, Shannon N Westin, Lois M Ramondetta, David M Gershenson, Anil K Sood, R Tyler Hillman

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions.

OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary.

STUDY …

Effect Of Delayed Cell Infusion In Patients With Large B-Cell Lymphoma Treated With Chimeric Antigen Receptor T-Cell Therapy, Andrew P Jallouk, Naishu Kui, Ryan Sun, Jason R Westin, Raphael E Steiner, Ranjit Nair, Loretta J Nastoupil, Luis E Fayad, Ajlan Al Zaki, Misha Hawkins, Sherry Adkins, Mansoor Noorani, Kaberi Das, Jared Henderson, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Christopher R Flowers, Sattva S Neelapu, Sairah Ahmed, Paolo Strati

Faculty, Staff and Student Publications

Complications occurring after lymphodepleting chemotherapy (LDC) may delay chimeric antigen receptor (CAR) T-cell infusion. The effect of these delays on clinical outcomes is unclear. We performed a retrospective analysis of 240 patients with relapsed/refractory large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel (axi-cel) and identified 40 patients (16.7%) who had delay in axi-cel infusion. Of these, 85% had delay due to infection. At time of LDC initiation, patients with delayed infusion had lower absolute neutrophil count (P=0.006), lower platelets (P=0.004), lower hemoglobin (P5 days (4.6 vs. 8.2 months; P=0.036), but not 1 day (5.7 vs. 8.2 months; P=0.238). Following propensity …

A 5-Year Longitudinal Structural Equation Model Of Social Isolation And Probable Major Depression Among Participants With Spinal Cord Injury, Chao Li, Susan Newman Phd, Rn, Crrn, Faan, Jillian M. Clark, James S. Krause

Publications

OBJECTIVE: To develop longitudinal structural models of social isolation and probable major depression (PMD) over a 5-year interval among participants with spinal cord injury (SCI). DESIGN: Longitudinal structural equation modeling of self-report assessments collected during two follow-ups (2013 as Time 1, 2018 as Time 2) of a 45-year multicohort longitudinal study. Participants (n = 557) were identified from a specialty hospital in the Southeastern United States and two Midwestern hospitals and were initially enrolled in 1973-1974, 1984-1985, 1993-1994, or 2003-2004. PMD symptomology was measured by the Patient Health Questionnaire-9 (PHQ-9) and was defined by PHQ-9 scores ≥ 10. Social isolation …

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum And Novel Clinical Observations In 241 Patients, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Enid S. Chelva, Sean Armstrong, Jose S. Pulido, Rebecca Procopio, Andrea L. Vincent, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Giulio Antonelli, Lucilla Barbano, João P. Marques, Sara Geada, Ana L. Carvalho, Wei C. Tang, Choi M. Chan, Camiel J. F. Boon, Jonathan Hensman, Ta-Ching Chen, Chien-Yu Lin, Pei-Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon, John R. Grigg, Robyn V. Jamieson, Elisa E. Cornish, Benjamin M. Nash, Shyamanga Borooah, Lauren N. Ayton, Alexis Ceecee Britten-Jones, Thomas L. Edwards, Jonathan B. Ruddle, Abhishek Sharma, Rowan G. Porter, Tina M. Lamey, Terri L. Mclaren, Samuel Mclenachan, Danial Roshandel, Fred K. Chen

Wills Eye Hospital Papers

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations.

RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, …

Outcomes Of Infectious Panuveitis Associated With Simultaneous Multi-Positive Ocular Fluid Polymerase Chain Reaction, Viet Q. Chau, John W. Hinkle, Chris Y. Wu, Parastou Pakravan, Vincent Volante, Jesse D. Sengillo, Patrick C. Staropoli, Darlene Miller, Nicolas A. Yannuzzi, Thomas A. Albini

Wills Eye Hospital Papers

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling.

METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021.

RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n …

Travel-Time Disparities In Access To Proton Beam Therapy For Cancer Treatment, Todd Burus, Alexander Vanhelene, Michael Rooney, Krystle Lang Kuhs, W. Jay Christian, Christopher Mcnair, Sanjay Mishra, Arnold Paulino, Grace Smith, Steven Frank, Jeremy Warner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

IMPORTANCE: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials.

OBJECTIVE: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study analyzed travel times to proton facilities in …

Patterns Of Undertreatment And Overtreatment In Adjuvant Radiotherapy For Early-Stage Endometrial Cancer Based On Molecular Classification, Otilia Ciobanu, Yixuan He, Alicia R Martin, Jill S Remick, Joseph W Shelton, Tony Y Eng, David C Qian

Faculty, Staff and Student Publications

The quality improvement study examines the use of risk-adaptive adjuvant radiotherapy in women with non–mismatch repair deficiency endometrial cancer.

Primary Care Patient Interests In Joining A Planned Multi-Cancer Early Detection Clinical Trial, Ronald E. Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn V. Davis, William T. Leach, Christopher V. Chambers

Department of Medical Oncology Faculty Papers

INTRODUCTION: Clinical trials are being conducted and are being planned to assess the safety and efficacy of multi-cancer early detection (MCED) tests for use in cancer screening. This study aimed to determine the feasibility of primary care patient outreach in recruiting participants to a planned MCED clinical trial, assess patient interest in trial participation, and measure decisional conflict related to participation.

METHODS: The research team used the electronic medical record of a large, urban health care system to identify primary care patients 50-80 years of age who were potentially eligible for a planned MCED trial. We mailed information about the …

Ictal Central Apnea Is Predictive Of Mesial Temporal Seizure Onset: An Intracranial Investigation, Nuria Lacuey, Blanca Talavera, Oman Magana-Tellez, Oscar Mancera-Páez, Norma Hupp, Xi Luo, Johnson P Hampson, Jaison Hampson, M R Sandhya Rani, Manuela Ochoa-Urrea, Omar A Alamoudi, Stephen Melius, Sandipan Pati, Jay Gavvala, Nitin Tandon, John C Mosher, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy.

Methods: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed.

Results: ICA was seen in 55 of 179 (30.7%) …

Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza

Division of Cardiology Faculty Papers

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.

MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and …

Use Of Electronic Nicotine Delivery Systems And Age Of Asthma Onset Among Us Adults And Youths, Adriana Pérez, Sarah Valencia, Pushan P Jani, Melissa B Harrell

Faculty, Staff and Student Publications

Importance: The association of use of electronic nicotine delivery systems (ENDS) with the age of asthma onset is unknown.

Objective: To explore the association of past 30-day ENDS use with the age of asthma onset in adults and youths who did not have asthma or chronic obstructive pulmonary disease and never used cigarettes.

Design, setting, and participants: This cohort study was a secondary analysis of waves 1 to 6 of the US nationally representative Population of Tobacco and Health Study (2013-2021). Eligible participants included adults (≥18 years) and youths (12-17 years) who did not have asthma or chronic obstructive pulmonary …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

A Randomized Trial Of Two Remote Health Care Delivery Models On The Uptake Of Genetic Testing And Impact On Patient-Reported Psychological Outcomes In Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, And Testing (Generate) Study, Nicolette J Rodriguez, C Sloane Furniss, Matthew B Yurgelun, Chinedu Ukaegbu, Pamela E Constantinou, Ileana Fortes, Alyson Caruso, Alison N Schwartz, Jill E Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H Nelson, Sydney Okumura, Alicia Y Zhou, Tara B Coffin, Hajime Uno, Miki Horiguchi, Allyson J Ocean, Florencia Mcallister, Andrew M Lowy, Alison P Klein, Lisa Madlensky, Gloria M Petersen, Judy E Garber, Scott M Lippman, Michael G Goggins, Anirban Maitra, Sapna Syngal

Faculty, Staff and Student Publications

Background & aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session …

Somatic Gene Mutation Patterns And Burden Influence Outcomes With Enasidenib In Relapsed/Refractory Idh2-Mutated Aml, Alberto Risueño, Wendy L See, Iryna Bluemmert, Stéphane De Botton, Courtney D Dinardo, Amir T Fathi, Andre C Schuh, Pau Montesinos, Paresh Vyas, Thomas Prebet, Anita Gandhi, Maroof Hasan

Faculty, Staff and Student Publications

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this …

Treatments Perceived To Be Helpful For Neuropathic Pain After Traumatic Spinal Cord Injury: A Multicenter Cross-Sectional Survey Study, Thomas N Bryce, Chung-Ying Tsai, Andrew D Delgado, Sara J Mulroy, Abigail Welch, Diana D Cardenas, Heather B Taylor, Elizabeth R Felix

Faculty, Staff and Student Publications

DESIGN: Cross-sectional survey.

OBJECTIVE: To evaluate the perceived helpfulness of pharmacological and non-pharmacological interventions and their combinations for neuropathic pain (NeuP) and subcategories of NeuP after spinal cord injury (SCI).

SETTING: Six Spinal Cord Injury Model System Centers.

METHODS: Three hundred ninety one individuals at least one year post traumatic SCI were enrolled. A telephone survey was conducted to determine the pharmacologic and non-pharmacologic treatments used in the last 12 months for each participant's three worst pains, whether these treatments were "helpful", and if currently used, each treatments' effectiveness.

RESULTS: Two hundred twenty participants (56%) reported 354 distinct NeuPs. Pharmacological …

Cross-Cohort Replicable Resting-State Functional Connectivity In Predicting Symptoms And Cognition Of Schizophrenia, Chunzhi Zhao, Rongtao Jiang, Juan Bustillo, Peter Kochunov, Jessica A Turner, Chuang Liang, Zening Fu, Daoqiang Zhang, Shile Qi, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia (SZ) is a debilitating mental illness characterized by adolescence or early adulthood onset of psychosis, positive and negative symptoms, as well as cognitive impairments. Despite a plethora of studies leveraging functional connectivity (FC) from functional magnetic resonance imaging (fMRI) to predict symptoms and cognitive impairments of SZ, the findings have exhibited great heterogeneity. We aimed to identify congruous and replicable connectivity patterns capable of predicting positive and negative symptoms as well as cognitive impairments in SZ. Predictable functional connections (FCs) were identified by employing an individualized prediction model, whose replicability was further evaluated across three independent cohorts (BSNIP, SZ …

Light Scattering By Vitreous Of Humans With Vision Degrading Myodesopsia From Floaters, Alba M Paniagua-Diaz, Justin H Nguyen, Pablo Artal, Wei Gui, J Sebag

Faculty, Staff and Student Publications

PURPOSE: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL.

METHODS: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission …

Practice Facilitation And Peer Coaching For Uncontrolled Hypertension Among Black Individuals: A Randomized Clinical Trial, Monika M Safford, Doyle M Cummings, Jacqueline R Halladay, James M Shikany, Joshua Richman, Suzanne Oparil, James Hollenberg, Alyssa Adams, Muna Anabtawi, Lynn Andreae, Elizabeth Baquero, Joanna Bryan, Debra Sanders-Clark, Ethel Johnson, Erica Richman, Orysya Soroka, Jimmy Tillman, Andrea L Cherrington

Faculty, Staff and Student Publications

IMPORTANCE: Rural Black participants need effective intervention to achieve better blood pressure (BP) control.

OBJECTIVE: Among Black rural adults with persistently uncontrolled hypertension attending primary care clinics, to determine whether peer coaching (PC), practice facilitation (PF), or both (PCPF) are superior to enhanced usual care (EUC) in improving BP control.

DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized clinical trial was conducted in 69 rural primary care practices across Alabama and North Carolina between September 23, 2016, and September 26, 2019. The participating practices were randomized to 4 groups: PC plus EUC, PF plus EUC, PCPF plus EUC, and EUC alone. …

Azacitidine, Venetoclax, And Gilteritinib In Newly Diagnosed And Relapsed Or Refractory Flt3-Mutated Aml, Nicholas J Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Lewis F Nasr, Walid Macaron, Musa Yilmaz, Gautam Borthakur, Guillermo Montalban-Bravo, Guillermo Garcia-Manero, Ghayas C Issa, Kelly S Chien, Elias Jabbour, Cedric Nasnas, Xuelin Huang, Wei Qiao, Jairo Matthews, Christopher J Stojanik, Keyur P Patel, Regina Abramova, Jennifer Thankachan, Marina Konopleva, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Purpose: Azacitidine plus venetoclax is a standard of care for patients with newly diagnosed AML who are unfit for intensive chemotherapy. However, FLT3 mutations are a common mechanism of resistance to this regimen. The addition of gilteritinib, an oral FLT3 inhibitor, to azacitidine and venetoclax may improve outcomes in patients with FLT3-mutated AML.

Methods: This phase I/II study evaluated azacitidine, venetoclax, and gilteritinib in two cohorts: patients with (1) newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy or (2) relapsed/refractory FLT3-mutated AML (ClinicalTrials.gov identifier: NCT04140487). The primary end points were the maximum tolerated dose …

Survival Disparities In Non-Hispanic Black And White Cervical Cancer Patients Vary By Histology And Are Largely Explained By Modifiable Factors, Calen W Kucera, Nicole P Chappell, Chunqiao Tian, Michael T Richardson, Christopher M Tarney, Chad A Hamilton, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christine Rojas, Collin A Sitler, Lari Wenzel, Ann Klopp, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Timothy D O'Connor, Craig D Shriver, Nicholas W Bateman, Thomas P Conrads, Neil T Phippen, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma …

Optimizing Outpatient Radiation Oncology Consult Workflow By Using Time-Driven Activity-Based Costing: Efficiency And Financial Impacts, Julius Weng, Shane Mesko, Gregory Chronowski, Percy Lee, Seungtaek Choi, Prajnan Das, Albert C Koong, Katy French, Thomas Aloia, Richie Ehlers, Dorothy Elrod-Joplin, Ashley Kerr, Regina Smith, Wendi Martinez, Elizabeth Bloom, Shalin J Shah, Matthew S Ning, Zhongxing Liao, Joseph Herman, Shalini Moningi, Amy C Moreno, Quynh-Nhu Nguyen

Faculty, Staff and Student Publications

PURPOSE: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics.

METHODS: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were …

Kras Allelic Variants In Biliary Tract Cancers, Gordon Taylor Moffat, Zishuo Ian Hu, Funda Meric-Bernstam, Elisabeth Kathleen Kong, Dean Pavlick, Jeffrey S Ross, Karthikeyan Murugesan, Lawrence Kwong, Anaemy Danner De Armas, Anil Korkut, Milind Javle, Jennifer J Knox

Faculty, Staff and Student Publications

IMPORTANCE: Biliary tract cancers (BTCs) contain several actionable molecular alterations, including FGFR2, IDH1, ERBB2 (formerly HER2), and KRAS. KRAS allelic variants are found in 20% to 30% of BTCs, and multiple KRAS inhibitors are currently under clinical investigation.

OBJECTIVES: To describe the genomic landscape, co-sequence variations, immunophenotype, genomic ancestry, and survival outcomes of KRAS-mutated BTCs and to calculate the median overall survival (mOS) for the most common allelic variants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, multicenter, pooled cohort study obtained clinical and next-generation sequencing data from multiple databases between January 1, 2017, and December 31, 2022. These databases included Princess …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Automated, High-Throughput Platform To Generate A High-Reliability, Comprehensive Rectal Cancer Database, Neal Bhutiani, Mahmoud M G Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Mark Knafl, Olivia Ratliff, Uditha P Fernando, Anastasia Turin, Fadl A Zeineddine, Jeff Jin, Kristin Alfaro-Munoz, Drew Goldstein, George J Chang, Scott Kopetz, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.

Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and …

Genomic Landscape Of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens For Immunoprevention, Ana M Bolivar, Fahriye Duzagac, Nan Deng, Laura Reyes-Uribe, Kyle Chang, Wenhui Wu, Charles M Bowen, Melissa W Taggart, Selvi Thirumurthi, Patrick M Lynch, Y Nancy You, Jesus Rodriguez-Pascual, Steven M Lipkin, Scott Kopetz, Paul Scheet, Gregory A Lizee, Alexandre Reuben, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Background & aims: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers.

Methods: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 …

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Student Publications

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

Design, setting, and participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Revisiting Feeding Tube Utilization In Oropharynx Cancer: 6-Year Prospective Registry Analysis, Brady J Anderson, Amy C Moreno, Yun Qing, J Jack Lee, Faye M Johnson, Miriam N Lango, Carly E A Barbon, Lavanya Tripuraneni, Ariana Sahli, Vicki Piper, Neil Gross, Clifton D Fuller, Stephen Y Lai, Jeffrey N Myers, Katherine A Hutcheson

Faculty, Staff and Student Publications

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients.

STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021.

SETTING: Single-institution NCI-Designated Comprehensive Cancer Center.

METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during …

Genome-Wide Association Analyses Of Breast Cancer In Women Of African Ancestry Identify New Susceptibility Loci And Improve Risk Prediction, Guochong Jia, Jie Ping, Xingyi Guo, Yaohua Yang, Ran Tao, Bingshan Li, Stefan Ambs, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Dezheng Huo, Esther M John, Christopher I Li, James L Li, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Xiao-Ou Shu, Melissa A Troester, Song Yao, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Huijun Qian, Haoyu Zhang, Christine B Ambrosone, Qiuyin Cai, Jirong Long, Julie R Palmer, Christopher A Haiman, Wei Zheng

Faculty, Staff and Student Publications

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Is Routine Use Of External Spinal Orthoses Necessary After Operative Stabilization Of Cervical Spine Injuries?, Derek Moody, James Showery, Ran Lador, Isaac Hernandez, Mark L Prasarn

Faculty, Staff and Student Publications

Study design: Retrospective Review.

Objective: The purpose of this study is to evaluate the efficacy of postoperative cervical orthoses to prevent fixation failure and loss of reduction after operative treatment of cervical spine fractures.

Summary of background data: While cervical orthoses are most times tolerated in trauma patients, it is not clear that postoperative bracing is effective at reducing the rate of fixation failure or nonunion in this patient population. Cervical collars may delay rehabilitation, increase the risk of dysphagia and aspiration, and can contribute to skin breakdown.

Methods: All patients who underwent operative stabilization for cervical spine injuries at …

Artificial Intelligence-Powered Assessment Of Pathologic Response To Neoadjuvant Atezolizumab In Patients With Nsclc: Results From The Lcmc3 Study, Sanja Dacic, William D Travis, Jennifer M Giltnane, Filip Kos, John Abel, Stephanie Hilz, Junya Fujimoto, Lynette Sholl, Jon Ritter, Farah Khalil, Yi Liu, Amaro Taylor-Weiner, Murray Resnick, Hui Yu, Fred R Hirsch, Paul A Bunn, David P Carbone, Valerie Rusch, David J Kwiatkowski, Bruce E Johnson, Jay M Lee, Stephanie R Hennek, Ilan Wapinski, Alan Nicholas, Ann Johnson, Katja Schulze, Mark G Kris, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate.

Methods: We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = …