Digital Commons Network^™

Case Report: Fia Plus Venetoclax In A Patient On Hemodialysis, Jacob E Herstein, Kayleigh R Marx, J Michael Savoy, Wei Ying Jen, Musa Yilmaz, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Tapan M Kadia, Naval G Daver, Courtney D Dinardo

Faculty, Staff and Student Publications

The safe and effective delivery of curative cytotoxic chemotherapy for acute myeloid leukemia (AML) in patients receiving intermittent hemodialysis (IHD) for end-stage renal disease (ESRD) remains a clinical challenge; pharmacological and logistical barriers necessitate close interdisciplinary coordination. In this case, we report a 65-year-old female patient with chronic ESRD on IHD and newly diagnosed AML who achieved complete remission (CR) after treatment with fludarabine, idarubicin, and cytarabine plus venetoclax (i.e., FIA + venetoclax).

Autophagy Cargo Profiles In Skeletal Muscle During Starvation And Exercise, Mohd Farhan, Shangze Lyu, Trezze P Nguyen, Dakai Zhang, Hong Liang, Yong Zhou, Yu A An, Jun Wang, Hongyuan Yang, Guangwei Du, Yang Liu

Faculty, Staff and Student Publications

Autophagy is a cellular process to clear unwanted and dysfunctional cellular cargoes, which are sequestered in autophagosomes before their delivery to lysosomes for degradation. Autophagy cargo selection, mediated by cargo receptors, varies across cell types and conditions. Understanding the cargo features is essential for elucidating autophagy's function in specific physiological or pathological contexts. Here, we present a simple and rapid method for isolating LC3B-positive autophagosomes from the tissues of GFP-LC3 transgenic mice, a widely used autophagy reporter model, without relying on the complex ultracentrifugation steps required by traditional methods. When combined with quantitative proteomics, this approach enables efficient in vivo …

Novel Pencil-Beam Scanning Proton Lattice Radiation Therapy For The Treatment Of Bulky Liver Cancer: Dosimetric Comparison With Vmat-Lattice Radiotherapy, Yuting Li, Rachael M Martin-Paulpeter, Christine V Chung, Miguel A Aguilar, Carlos A Matias, Adrian Delgado, Saurabh S Nair, Laurence E Court, Luis Perles, Narayan Sahoo, Ronald X Zhu, Falk Poenisch, David B Flint, Gabriel O Sawakuchi, Sam Beddar, Eugene Koay, Jamie S Baker, Ethan B Ludmir, Joshua S Niedzielski

Faculty, Staff and Student Publications

Background: Spatially fractionated radiotherapy (SFRT) delivered as lattice radiotherapy (LRT) creates high-dose 'vertex' subvolumes (VTVH) embedded within low-dose 'valley' regions (VTVL) to intensify intratumoral dose while minimizing radiation dose and toxicity to organs at risk (OARs). We developed a pencil-beam scanning (PBS) intensity modulated proton therapy (IMPT) LRT planning approach and dosimetrically compared it directly with contemporary photon-based volume modulated arc therapy (VMAT) LRT for liver cancer with bulky tumors.

Methods: Twenty-one retrospective liver cases were replanned in RayStation to a single fraction of 20 Gy to VTVH with explicit VTVL sparing (mean dose < 5Gy). Primary dosimetric endpoints were VTVH D80 and VTVL mean dose (analogous to mean valley dose), with secondary endpoints of VTVH/VTVL ratios (PVDR-like metrics at D80/D90/D100), VTVL D5/D80, GTV D10/D90, and planning risk volume (PRV) 0.03 cm³ hotspots. Statistical analysis consisted of paired tests (t-test or Wilcoxon signed-rank) after assessing data normality (Shapiro-Wilk tests) and using α=0.05 for significance.

Results: Compared with photon VMAT-LRT, IMPT-LRT …

A Prospective Cohort Study On Stereotactic Radiotherapy In The Management Of Dural Recurrence Of Olfactory Neuroblastoma, Christopher D Goodman, Franco Demonte, Theresa P Nguyen, Adam S Garden, Catherine He Wang, Xin A Wang, Kevin Diao, Anna Lee, Jay Reddy, Amy Moreno, Michael Spiotto, Clifton D Fuller, David Rosenthal, Renata Ferrarotto, Shaan M Raza, Shirley Y Su, Andrew Warner, Ehab Hanna, Jack Phan

Faculty, Staff and Student Publications

Background: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population.

Methods: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed.

Results: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression …

Disulfidptosis And Its Emerging Relevance In Cancer And Immunity, Qidong Li, Shengrong Wu, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Disulfidptosis is a recently identified form of regulated cell death (RCD) triggered by disulfide stress when cystine uptake via solute carrier family 7 member 1 (SLC7A11) overwhelms the cell's reducing capacity. Unlike apoptosis or other "cell suicide" pathways, disulfidptosis likely represents a "cell sabotage" mechanism, defined by aberrant disulfide bonding and catastrophic actin cytoskeleton collapse. In this Perspective, we examine the paradoxical role of SLC7A11 as both a ferroptosis protector and a disulfidptosis trigger, and the mechanistic hallmarks of disulfidptosis. We highlight emerging therapeutic strategies to target disulfidptosis in cancer, including glucose transporter inhibition, redox-targeting agents, and nanomaterial-based approaches, and …

E2f1 Overexpression Reduces Aging-Associated Dna Damage In Cultured Cerebral Endothelial Cells And Improves Cognitive Performance In Aged Mice, Sheelu Monga, Samantha Flores, Maria Pilar Blasco-Conesa, Syed M Rahman, Brian Noh, Pedram Peesh, Bhanu Priya Ganesh, Sean P Marrelli, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

As we age, cerebral endothelial cells (CECs) are less efficient in maintaining genome integrity and accumulate DNA damage. DNA damage in the brain endothelium can lead to the impairment of the blood–brain barrier (BBB), which is a major factor in brain dysfunction and dementia. Thus, identifying factors that regulate DNA repair in the brain endothelium can prevent brain dysfunction associated with aging. E2F1 is a transcription factor that regulates the expression of genes associated with DNA repair, among other functions. We hypothesize that E2F1 is downregulated in the brain vasculature of mice with aging and that E2F1 upregulation can improve …

Keygan: Synthetic Keystroke Data Generation In The Context Of Digital Phenotyping, Alejandro Acien, Aythami Morales, Luca Giancardo, Ruben Vera-Rodriguez, Ashley A Holmes, Julian Fierrez, Teresa Arroyo-Gallego

Faculty, Staff and Student Publications

Objective: This paper aims to introduce and assess KeyGAN, a generative modeling-based keystroke data synthesizer. The synthesizer is designed to generate realistic synthetic keystroke data capturing the nuances of fine motor control and cognitive processes that govern finger-keyboard kinematics, thereby paving the way to support biomarker development for psychomotor impairment due to neurodegeneration.

Methods: KeyGAN is designed with two primary objectives: (i) to ensure high realism in the synthetic distributions of the keystroke features and (ii) to analyze its ability to replicate the subtleties of natural typing for enhancing biomarker development. The quality of synthetic keystroke data produced by KeyGAN …

A Novel Automated Ct Biomarker To Predict Outcomes In Acute Ischemic Stroke: Net Water Uptake, Monica Mallavarapu, Hyun Woo Kim, Ananya Iyyangar, Sergio Salazar-Marioni, Albert J Yoo, Luca Giancardo, Sunil A Sheth, Jerome A Jeevarajan

Faculty, Staff and Student Publications

Background: Recent trials of large core thrombectomy have shown that our traditional understanding of infarct characteristics and reperfusion benefit may be incomplete for patients with acute ischemic stroke (AIS). The Alberta Stroke Program Early CT Score (ASPECTS) has wide inter-rater variability, and modern studies have also shown that reperfusion therapies can benefit some patients regardless of the ASPECTS. Reproducible imaging metrics that account for the degree of hypo-attenuation on non-contrast computed tomography (NCCT) may be better suited to guide treatments. Here, we evaluate Net Water Uptake (NWU), a novel NCCT metric that can be calculated in a rapid and automated …

Neuroprotective Role Of Ding Protein In Fetal Alcohol Spectrum Disorders And Depression, Nune Darbinian, Monica Hampe, Nana Merabova, Tamara Tatevosian-Geller, Laura Goetzl, Mary F Morrison, Gabriel Tatevosian, Malgorzata Simm, Eric Chabriere, Huaqing Zhao, Shohreh Amini, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: An estimated 20% of women consume alcohol during pregnancy, and 10% of women receive antidepressants during their pregnancy. Women with depression are more likely to use alcohol (EtOH) in early pregnancy and are more likely to have a child with one of the fetal alcohol spectrum disorders (FASD). Previously, we provided evidence in rat neurons in vitro that DING phosphatase (p38SJ, a member of the DINGGG family of proteins that has neuroprotective effects under conditions of cellular stress) was neuroprotective against EtOH-mediated toxicity. Now, we examine the effects of DING, alone or in combination with EtOH and serotonergic (5-HT) …

Comparison Of Primary Care Experiences And Outpatient Health Service Utilization Among Black And Latino Homeless-Experienced Veterans: An Analysis Of Patient-Centered Medical Homes, Melissa Chinchilla, Audrey L Jones, Aerin Derussy, Michael F Green, Lillian Gelberg, Alexander S Young, Jack Tsai, Sonya E Gabrielian, Stefan G Kertesz

Faculty, Staff and Student Publications

Objectives: To examine whether, among persons with recent homeless experience, minoritized clients rate primary care differently from non-minoritized clients in Veterans Affairs (VA) mainstream and homeless tailored clinics, through the largest survey of homeless-experienced Black, White, and Latino Veterans to date.

Methods: Surveys were collected from HEVs in Homeless-tailored Patient-Aligned Care Teams (HPACTs) and mainstream Patient Aligned Care Teams (PACTs; n = 4894). We tested multivariable associations between race/ethnicity, clinic (HPACT vs mainstream-PACT), and their interaction, on care experience ratings and service utilization.

Results: There were no major differences in care ratings by race/ethnicity; medical and social vulnerability factors were …

Racial And Ethnic Disparities In Longitudinal Trajectories Of Cardiovascular Risk Factors In Us Middle-Aged And Older Adults, Matthew E Dupre, Radha Dhingra, Hanzhang Xu, Scott M Lynch, Qing Yang, Cassie Ford, Michael D Green, Ying Xian, Ann Marie Navar, Eric D Peterson

Faculty, Staff and Student Publications

Background: Racial and ethnic disparities in cardiovascular disease (CVD) risk factors are well-documented. However, racial and ethnic differences in the longitudinal changes among multiple CVD risk factors are unknown.

Methods: We used prospective cohort data of U.S. adults aged ≥50 in the 2006-2016 Health and Retirement Study. Group-based multi-trajectory models characterized age-related trajectories of systolic blood pressure ([BP] mmHg), non-HDL cholesterol (mg/dL), diabetes mellitus (DM), and smoking. Racial and ethnic differences in the multi-trajectory profiles were examined using multinomial logistic regression. Karlson-Holm-Breen methods were used to assess factors contributing to these associations.

Results: Among 10,292 participants (median age: 61), approximately …

Helping Everyone Achieve A Lifetime Of Health - Future Addiction Scientist Training Program Outcomes, Asfand B Moosa, Christina M Segura, Ammar D Siddiqi, Hinal Patel, Tzuan A Chen, Anastasia Rogova, Marcy Zere, Ezemenari M Obasi, Lorraine R Reitzel

Faculty, Staff and Student Publications

Objectives: Addiction to alcohol, tobacco, and/or other drugs (ATOD) remains a leading cause of cancer and a contributor to diabetes and cardiovascular diseases, disproportionately affecting marginalized and minoritized groups. Social and structural inequities including limited healthcare access, employment instability, inadequate housing, and environmental stressors increase these risks. A diverse scientific workforce is necessary to mitigate ATOD-related health disparities; yet underrepresentation persists in ATOD research. Helping Everyone Achieve a LifeTime of Health-Future Addiction Scientist Training (HEALTH-FAST) is a NIDA funded research education program that aims to reduce ATOD-related disparities by training future scholars in addiction science and health equity.

Methods: From …

New Anhydramnios After 22 Weeks And Pulmonary Hypoplasia, Aaron W Roberts, Margaret Clement, Suzanne Marie Lopez, Rita Swinford, Percy Pacora Portella, Edgar Hernandez-Andrade, Matthew Rysavy, Anthony Johnson

Faculty, Staff and Student Publications

Introduction: Anhydramnios due to renal failure prior to 22 weeks of gestational age (WGA) is associated with lethal pulmonary hypoplasia but after 22 WGA outcomes are less clear. We evaluated whether these fetuses, with new anhydramnios after 22 WGA, incur significant risk of severe neonatal pulmonary morbidity.

Methods: This retrospective study of singleton pregnancies diagnosed with new-onset renal anhydramnios after 22 WGA following verifiable normal AFI on ultrasound before 22 WGA from 2021 to 2023. Cases with bilateral renal agenesis, premature rupture of membranes, and nonrenal malformations were excluded.

Results: During the study period 53,698 s trimester ultrasound examinations were …

The Deceleration Dilemma: Leveraging The Relationship Between Quadriceps Function And Deceleration To Optimize Return To Sport, Steven Higbie, Christopher Gallina, Russ Paine, Lane Bailey, Walter R Lowe

Faculty, Staff and Student Publications

Decelerations frequently occur during sport and are often associated with non-contact knee injury mechanisms. Though decelerations place a high eccentric demand on the quadriceps, little is known about the relationship between quadriceps function and deceleration performance. Traditional functional testing batteries often over-estimate quadriceps function and lack assessments of deceleration performance, while current deceleration testing is often heavily reliant on technology and performed at shallow angles. The purpose of this clinical commentary is to describe the relationship between deceleration and quadriceps function, suggest two clinical tests to assess deceleration performance, and provide exercise suggestions for improving deceleration performance. The authors believe …

Impact Of Preoperative And Residual Alpha Angle On Outcomes After Hip Arthroscopy, Jasmine Puria, Daniel Puczko, Christopher S Frey, James L Rogers, Alicia M Hymel, Candler G Mathews Iii, Thomas M Spears, Jaron Paul Sullivan

Faculty, Staff and Student Publications

Purpose: Femoroacetabular impingement syndrome (FAIS) can lead to pain, decreased mobility, and difficulty in performing activities of daily living. Symptoms can improve with surgery, often hip arthroscopy with osteoplasty. Radiological parameters such as the alpha angle can be utilized to determine the degree of cam morphology and assess resection after surgery. This study sought to evaluate the relationship between pre-operative alpha angle and the change in alpha angle on patient satisfaction post-surgical correction using the 12-item International Hip Outcome Tool (iHOT-12).

Patients and methods: Patients that underwent primary or revision hip arthroscopy with osteoplasty for FAIS by a single fellowship-trained …

Information Seeking Behaviors And Attitudes Of Wives Of Former Football Players Regarding Chronic Traumatic Encephalopathy, Summer D Ott, Sukhnandan K Cheema, Alexa Ryder, Philip Schatz, Lorie A Gonzalez, Jecenia Duran, Paul E Schulz

Faculty, Staff and Student Publications

This study examines CTE-related knowledge and information-seeking behaviors of caregivers of persons who are at high risk of CTE. Online survey responses were collected from 64 females, ages 18-74, who were married to former college, semiprofessional, or professional football players and were fluent in English. Ranging from 0 to 18, a score was calculated to represent level of CTE knowledge. Participants were classified into groups based on their spouse's reported symptoms and diagnosis. Approximately 87% of participants reported that their spouses have been diagnosed with a football-related concussion and were significantly more likely to seek out information from a healthcare …

Professional Baseball Pitchers Use Of Weighted Ball Training, Injury Incidence, And Time Loss: A Preliminary Study, Ellen Shanley, Thomas J Noonan, Michael J Kissenberth, Daniel Kline, Charles A Thigpen, Garrett S Bullock

Faculty, Staff and Student Publications

Background: Little is known about the injury risk associated with weighted ball use by professional baseball pitchers. The purpose of this study was to describe weighted ball training and injuries and compare injury rates between those professional pitchers using weighted ball training and those that did not use weighted ball training during the 2023 pre- and regular season.

Methods: This study, intended as a multi-year project, serves as an interim safety analysis after one year of follow up. Pitchers underwent routine physical examination and injury screening and were surveyed about their use of weighted baseball training. Throughout spring training and …

Effect Of Palatoplasty Technique On Otologic Outcomes In Children With Cleft Palate, Shaina W Gong, Paul Hung, Chioma G Obinero, Jose Barrera, Zi Yang Jiang, Matthew R Greives, Zhen Huang

Faculty, Staff and Student Publications

Background: In patients with cleft palate (CP), the impact of primary palatoplasty technique on otologic outcomes remains a major point of contention. While some studies report improved outcomes after certain techniques of palatal repair, there is a lack of consensus on the most effective procedure.

Objective: We sought to characterize the effects of primary palatoplasty technique on otologic outcomes in children with CP.

Methods: A single institution retrospective review of patients with CP who underwent primary palatoplasty (straight-line repair or Furlow Z-plasty) was performed. Primary outcomes of interest included time to placement of T-tubes, number of tympanostomy tube placements, tympanic …

Transnasal Humidified Rapid Insufflation Ventilatory Exchange (Thrive) For The Operative Management Of Retrograde Cricopharyngeus Dysfunction, Amy B Leming, Dylan G Vance, Andrew G Tritter, Zao Mike Yang

Faculty, Staff and Student Publications

Objective: Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) is a method of apneic oxygenation gaining popularity in upper aerodigestive surgery. Retrograde cricopharyngeus muscle dysfunction (RCPD) is characterized by the inability to belch, managed by intraoperative injection of botulinum toxin to the cricopharyngeus muscle (CPBI), often performed under general anesthesia with endotracheal intubation. We sought to assess the safety and efficacy of THRIVE when performing CPBI for RCPD.

Study design: We conducted a retrospective review of adult RCPD patients undergoing CPBI under general anesthesia with THRIVE.

Setting: The study was conducted at both the University of Texas Health Science Centers in …

Molecular, Histologic, And Clinical Characterization Of Methylation Class Pleomorphic Xanthoastrocytoma: An Analysis Of 469 Tumors, Christopher H Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osorio Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye-Jung Chung, Patrick J Cimino, Kyle S Conway, Jennifer Cotter, Felipe D'Almeida Costa, Karen Dazelle, Nima Etminam, Sima Esther Ferman, Igor Fernandes, Christina K Ferrone, Ahmed Gilani, Mark Gilbert, Jason Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz S Lopes, Qinwen Mao, Michael S Marshall, Matthew Mccord, Stewart G Neill, Jeffrey J Nirschl, Byram H Ozer, Werner Paulus, Marta Penas-Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael Vaubel, Nitin Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas Von Deimling, Kenneth Aldape

Faculty, Staff and Student Publications

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated.

Results: Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Advancing Randomized Clinical Trials In Surgery: Role Of Exception From Informed Consent, Central Institutional Review Board, And Bayesian Approaches, Amelia W Maiga, Rebecca A Snyder, Lillian S Kao, Mehul V Raval, Mayur B Patel, Martin L Blakely

Faculty, Staff and Student Publications

No abstract provided.

Reducing Computed Tomography Use For Appendicitis Evaluation In A Pediatric Emergency Department: A Multidisciplinary Quality Improvement Initiative, Jennifer Hockenbury, Monica E Lopez, Caroline M Godfrey, Martin L Blakely, Melissa Danko, Marta Hernanz-Schulman, S Barron Frazier

Faculty, Staff and Student Publications

Introduction: Appendicitis is the most common pediatric surgical emergency, and computed tomography (CT) remains an overused diagnostic test for appendicitis. Our institutional rate of CT utilization for suspected appendicitis was higher than in peer children's hospitals, so we aimed to reduce CT utilization during the evaluation of pediatric appendicitis from 31.3% to 15% within 12 months.

Methods: From September 2021 to October 2022, we conducted a multidisciplinary quality improvement initiative among patients evaluated for appendicitis in the pediatric emergency department (PED). Interventions included standardizing evaluation with a clinical practice guideline, an order set in the electronic medical record for clinical …

Moving From Prognostication To Prevention Of Ssis In Lmics, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Case Report: Successful Delivery Following Chemotherapy In A Pregnant Patient With Metastatic Smarcb1-Deficient Renal Medullary Carcinoma, Panayiotis D Kontoyiannis, Adam Kuykendal, Chad Tang, Jessica P Cheng, Beei Chan, Susan S Thomas, Priya Rao, Bora Lim, Pavlos Msaouel

Faculty, Staff and Student Publications

SMARCB1-deficient renal medullary carcinoma (RMC) is a rare and aggressive kidney cancer defined by the loss of SMARCB1 tumor suppressor and primarily affecting adolescents and young adults with sickle hemoglobinopathies. Approximately 7% of RMC cases, known as renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), lack sickle hemoglobinopathy. RMC does not respond to immune checkpoint inhibitors and antiangiogenic tyrosine kinase inhibitors, with chemotherapy being the main treatment. Here we present the first documented case of RMC diagnosed during pregnancy. A 24-year-old woman presented with right-sided back pain, leading to the discovery of a 6-cm right renal mass. Pathology confirmed RCCU-MP …

Comb-Boin12: A Utility-Based Bayesian Optimal Interval Design For Dose Optimization In Cancer Drug-Combination Trials, Mengyi Lu, Jingyi Zhang, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Drug combinations are increasingly utilized in cancer treatment to enhance drug effectiveness through synergistic therapeutic effects. However, determining the optimal biological dose combination (OBDC) in small-scale drug combination trials presents challenges due to the increased complexity of the dose space. To effectively optimize the dose combination of combined drugs, we propose a model-assisted design by extending the single-agent Bayesian optimal interval phase I/II (BOIN12) design. Our approach incorporates a utility function to balance the trade-off between risk and benefit and directly models the utility of each dose by constructing a quasi-beta-binomial model. A key advantage of our design is the …

Consolidation Alk Tyrosine Kinase Inhibitors Versus Durvalumab Or Observation After Chemoradiation In Unresectable Stage Iii Alk-Positive Nsclc, Amin H Nassar, Ritujith Jayakrishnan, Jamie Feng, Frances Shepherd, Elio Adib, Justin M Cheung, Jessica J Lin, Yufei Liu, Steven H Lin, Kaushal Parikh, Arthi Sridhar, Purnima Shakya, Thomas J Dilling, David Kaldas, Jhanelle E Gray, Anastasiya Lobachov, Jair Bar, Heike Luders, Christian Grohe, Shruti Gupta, Ticiana Leal, Bailey Fitzgerald, Fionnuala Crowley, Yu Fujiwara, Thomas U Marron, Molly Wilgucki, Joshua Reuss, Luxi Chen, Kamya Sankar, Jacqueline V Aredo, Joel W Neal, Heather A Wakelee, Rohit Thummalapalli, Helena Yu, Ryan Whitaker, Ana Velazquez, Meera Ragavan, Alessio Cortellini, David J Kwiatkowski, Abdul Rafeh Naqash, Sarah B Goldberg, So Yeon Kim

Faculty, Staff and Student Publications

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related …

Correlation Of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes In Total Pancreatectomy With Islet Autotransplantation, Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin

Faculty, Staff and Student Publications

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including …

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose

To combine deep learning and biology-based modeling to predict the response of locally advanced, triple-negative breast cancer before initiating neoadjuvant chemotherapy (NAC).

Materials and Methods

In this retrospective study, a biology-based mathematical model of tumor response to NAC was constructed and calibrated on a patient-specific basis using imaging data from patients enrolled in the MD Anderson A Robust TNBC Evaluation FraMework to Improve Survival trial (ARTEMIS; ClinicalTrials.gov registration no. NCT02276443) between April 2018 and May 2021. To relate the calibrated parameters in the biology-based model and pretreatment MRI data, a convolutional neural network (CNN) was employed. The CNN …