Medical Specialties Commons^™

Multi-Omic Profiling Provides Insights Into The Heterogeneity, Microenvironmental Features, And Biomarker Landscape Of Small-Cell Lung Cancer, Mingchao Xie, Miljenka Vuko, Shashank Saran, Siyu Liu, Andrew G Chambers, Hana Baakza, Helen K Angell, Felicia Ng, Carl M Gay, Robert J Cardnell, Felix J Segerer, Alma Andoni, Jaime Rodriguez-Canales, Paul M Waring, Markus Schick, J Carl Barrett, Lauren A Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Background: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

Methods: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

Results: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest …

Inhibition Of Clostridioides Difficile-Specific Dna Adenine Methyltransferase Cama By Analogs Of S‑Adenosyl‑L‑Methionine, Jujun Zhou, Youchao Deng, Dan Yu, Taraneh Hajian, Masoud Vedadi, Xing Zhang, Robert M Blumenthal, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapies, especially those inhibiting S-adenosyl-l-methionine (SAM)-dependent methylations of DNA, mRNA, and histones, have advanced rapidly in cancer treatment. However, these therapies remain underexplored for antibiotic development, despite the growing threat of antimicrobial resistance. Here, we screened a focused library of SAM analogs against the DNA adenine methyltransferase CamA specific to the enteric pathogen Clostridioides difficile. At the same time, we examined six other adenine methyltransferases, including two bacterial DNA methyltransferases and four human RNA methyltransferases having distinct RNA substrates. Compound 113 selectively inhibited CamA (IC50 = 0.15 μM). In addition, compound 67 inhibited Caulobacter crescentus CcrM …

Characterizing Circulating Rare Cells In Peripheral Blood For Detecting And Monitoring Multiple Myeloma And Precursor States, Stephanie N Shishido, Jeremy Mason, Mohamed Kamal, Sonia Maryam Setayesh, Amishi U Vora, David Berrios, Luz Yurany Moreno Rueda, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) arises from abnormal plasma cells (PCs) progressing from precursor states, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding this transition and progression to overt MM requires improved non-invasive strategies. We employed a liquid biopsy approach to detect and characterize circulating PCs across disease states in 68 patients (MGUS = 11, SMM = 21, NDMM = 19, RRMM = 17) using multi-channel immunofluorescence staining and machine learning-assisted rare event detection. PCs were identified by CD138 and B-cell maturation antigen (BCMA) expressions, with distinct phenotypic subpopulations stratifying disease states. The D | CD138 | …

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

From Standard To Stratified: Modeling Ntcp And Ear To Personalize Daily Mv-Cbct In Radiotherapy., Duong Thanh Tai, Luong Tien Phat, Tran Trung Kien, Duong Tuan Linh, Nguyen Ngoc Anh, Nguyen Quang Hung, Peter Sandwall, Parham Alaei, David Bradley, James C L Chow

Oncology Articles

PURPOSE: To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

METHODS: This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols …

A Scoping Review Of Factors Influencing The Implementation Of Liquid Biopsy For Cancer Care, Samran Sheriff, Maree Saba, Romika Patel, Georgia Fisher, Tanja Schroeder, Gaston Arnolda, Dan Luo, Lydia Warburton, Elin Gray, Georgina Long, Jeffrey Braithwaite, Helen Rizos, Louise Ann Ellis

Research outputs 2022 to 2026

Background: Liquid biopsy (LB) offers a promising, minimally invasive alternative to traditional tissue biopsies in cancer care, enabling real-time monitoring and personalized treatment. Despite its potential, the routine implementation of LB in clinical practice faces significant challenges. This scoping review examines the barriers and facilitators influencing the implementation of liquid biopsies into standard cancer care. Methods: Four academic databases (PubMed, Scopus, Embase, and Web of Science) were systematically searched without language restrictions. We included peer-reviewed articles that were published between January 2019 and March 2024 that focused on the implementation of LB in cancer care or described barriers and facilitators …

Effects Of Exercise Or Diet Or Combined Interventions On Treatment Efficacy Of Chemotherapy For Cancer: A Systematic Review, Cristina Crespo-Garcia, Francesco Bettariga, Dennis R. Taaffe, Carolyn J. Peddle-Mcintyre, John P. Campbell, Emily Jeffery, Anna Maria Markarian, Anita Borsati, Alice Avancini, Sara Pilotto, Daniel A. Galvao, Robert U. Newton

Research outputs 2022 to 2026

Purpose of Review: While exercise and dietary interventions in patients with cancer undergoing chemotherapy have been demonstrated to be safe and feasible and improve patient-reported outcomes, the effects on treatment efficacy have not been widely examined and remain unclear. This review aimed to examine the effects of exercise, dietary, and combined interventions on tumour response and time-to-event outcomes in patients with cancer undergoing chemotherapy. Recent Findings: A systematic review of intervention studies was conducted based on PRISMA guidelines Databases searched were PubMed, Medline, CINAHL, Embase, and Web of Science. Methodological quality and risk of bias were assessed using the RoB2 …

Pact Is Requisite For Prostate Cancer Cell Proliferation, Dianne J. Beveridge, Andrew J. Woo, Kirsty L. Richardson, Rikki A.M. Brown, Lisa M. Stuart, Manjot Singh, Andrew D. Redfern, Peter J. Leedman

Research outputs 2022 to 2026

PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein with defined antiviral defense and cytoplasmic RNA-induced silencing actions in mammals. We previously described a further role for PACT as a modulator of nuclear receptor (NR)-regulated gene expression. Here, we investigated the role of PACT in prostate cancer (PCa) using a loss-of-function approach. Depletion of PACT in multiple PCa cell lines resulted in a reduction in cell proliferation, but viability was maintained. RNA-sequencing analysis of LNCaP PCa cells ± PACT revealed a depletion of biological processes involved in cell cycle, mitochondrial function, and NR-response pathways in the PACT …

Periodizing Exercise Medicine Prescription For Patients With Cancer: A Narrative Opinion, Francesco Bettariga, Robert U. Newton, Chris Bishop, Luca Maestroni, Anita Borsati, Alice Avancini, Sara Pilotto, Dennis R. Taaffe, Daniel A. Galvão, G. Gregory Haff

Research outputs 2022 to 2026

Exercise has emerged as an effective therapeutic strategy in cancer management. Long-term supervised exercise programs, including resistance training and aerobic training, can improve body composition and physical fitness, modulate circulating factors (e.g., hormones, cytokines), enhance treatment tolerance, and reduce side effects, potentially influencing cancer progression and reducing mortality risk. Despite advancements in exercise oncology, opportunities remain to refine exercise prescription through the integration of advanced methodologies such as periodization and autoregulatory programming strategies. Periodization, a systematic approach to organizing training over time, has demonstrated benefits in general fitness and clinical populations but is underexplored in cancer care. Emerging evidence suggests …

Rac1 In Gastric Cancer: A Molecular Driver Of Invasion, Emt, And Therapeutic Resistance, Jianwen Li, Yahong Zhu, Ruifeng Duan, Yueli Tian, Xingang Li, Ying Song

Research outputs 2022 to 2026

Gastric cancer (GC) ranks as the fifth most common cancer worldwide and is the third main cause of cancer-related mortality, posing a substantial burden to global public health. Research suggests that targeted therapy and immunotherapy may become more effective treatment options for advanced, unresectable, or metastatic gastric cancer. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTP-binding protein within the Rac subfamily of the Rho GTPase family, is a critical molecule that promotes cancer cell invasion and metastasis by regulating signal transmission and promoting cell polarity. It has emerged as a key driver of tumor development and metastasis in …

Non-Pharmacological Supportive Care Interventions During Immunotherapy For People With Cancer: A Systematic Scoping Review And Future Directions, Morgan J. Farley, Brighid R. Scanlon, Megan Crichton, Ashley M. Bigaran, Amy C.M. Barnes, Nicolas H. Hart, Patsy M. Yates, Melissa L. Eastgate, Kim Alexander

Research outputs 2022 to 2026

Purpose: Immunotherapy has transformed cancer treatment and outcomes. Patients receiving immunotherapy often encounter immune-related and treatment-related adverse events, leading to substantial supportive care needs. Currently, no recommendations exist to guide the use of non-pharmacological supportive care interventions for people with cancer undergoing immunotherapy treatments. This review aims to summarise the available evidence regarding non-pharmacological supportive care strategies to inform future clinical management and research directions.

Methods: Six electronic databases (PubMed, CINAHL, EMBASE, PsycInfo, Web of Science and Scopus) were systematically searched for studies on non-pharmacological supportive care interventions for adults undergoing immunotherapy, published from October 2014 to October 2024.

Results: …

Effects Of Short- And Long-Term Exercise Training On Cancer Cells In Vitro: Insights Into The Mechanistic Associations, Francesco Bettariga, Dennis R. Taaffe, Daniel A. Galvão, Robert U. Newton

Research outputs 2022 to 2026

Exercise is a therapeutic approach in cancer treatment, providing several benefits. Moreover, exercise is associated with a reduced risk for developing a range of cancers and for their recurrence, as well as with improving survival, even though the underlying mechanisms remain unclear. Preclinical and clinical evidence shows that the acute effects of a single exercise session can suppress the growth of various cancer cell lines in vitro. This suppression is potentially due to altered concentrations of hormones (e.g., insulin) and cytokines (e.g., tumor necrosis factor alpha and interleukin 6) after exercise. These factors, known to be involved in tumorigenesis, may …

Exercise Medicine As Adjunct Therapy During Radiation For Cancer Of The Prostate To Improve Treatment Efficacy – Protocol For The Eradicate Study: A Phase Ii Randomised Controlled Trial, Oliver Schumacher, Robert U. Newton, Colin Tang, Raphael Chee, Sjoerd B. Vos, Ronny S. Low, David Joseph, Dennis R. Taaffe, Daniel A. Galvão

Research outputs 2022 to 2026

Background: Tumour hypoxia resulting from inadequate perfusion is common in many solid tumours, including prostate cancer, and constitutes a major limiting factor in radiation therapy that contributes to treatment resistance. Emerging research in preclinical animal models indicates that exercise has the potential to enhance the efficacy of cancer treatment by modulating tumour perfusion and reducing hypoxia; however, evidence from randomised controlled trials is currently lacking. The ‘Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE’ (ERADICATE) study is designed to investigate the impact of exercise on treatment response, tumour physiology, and adverse effects of treatment in prostate …

Integrating Spot-Scanning Proton Arc Therapy With Functional Avoidance Strategies To Reduce Pulmonary Toxicity, Yingxuan Chen, Peilin Liu, Xiaoda Cong, Edward Castillo, Richard Castillo, Inga Grills, Craig Stevens, Xiangkun Xu, Xiaoqiang Li, Yevgeniy Vinogradskiy, Xuanfeng Ding

Department of Radiation Oncology Faculty Papers

Background and purpose: Functional avoidance radiotherapy has emerged as a promising technique using functional imaging to minimize pulmonary toxicity by reducing doses to functional lung. This study aims to investigate the potential dose-volume advantages of a novel spot-scanning proton arc (SPArc) therapy for functional avoidance radiotherapy with four-dimensional computed tomography (4DCT)-based ventilation imaging.

Material and methods: Twenty-five patients from a prospective functional avoidance clinical trial treated with intensity-modulated photon radiotherapy were included. Robustly optimized intensity modulated proton therapy (IMPT) and SPArc plans were generated in RayStation. Functional lung contour was derived from the 4DCT-based ventilation imaging and utilized as an …

Incidence And Management Of Adverse Events Associated With Tebentafusp Treatment In Metastatic Uveal Melanoma: Pooled Safety Analysis Of 410 Patients, Takami Sato, Marcus O. Butler, Sophie Piperno-Neumann, Jessica C. Hassel, Paul Nathan, Alexander N. Shoushtari, Piotr Rutkowski, Richard D. Carvajal, Jean-Francois Baurain, Max Schlaak, Josep M. Piulats, Ryan J. Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M. Kirkwood, Alexandra Ikeguchi, Anthony M. Joshua, Mark R. Middleton, Ramakrishna Edukulla, Constance Pfeiffer, Joseph J. Sacco

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

PURPOSE: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T-cell engager, which can redirect T cells to target glycoprotein 100-positive cells, in metastatic uveal melanoma.

EXPERIMENTAL DESIGN: HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma enrolled in three clinical trials (IMCgp100-01, IMCgp100-102, and IMCgp100-202) who received ≥1 dose of tebentafusp were included. Safety data were pooled to evaluate the profile, onset, and management of treatment-related adverse events (TRAE). Adverse events of special interest included cytokine release syndrome (CRS), acute skin reactions (ASR), and liver function test elevations. Primary prophylaxis with medications was …

A Feasibility Study Of Sexual Organ-Dose Sparing Volumetric Modulated Arc Therapy In Female Low Rectal Cancer Patients Treated With Three-Dimensional Conformal Radiation Therapy, Margaret Downes, Victoria Olsen, Andre Williams, Rendi Sheu, Maria Thor, Lucy Greenwald, Vishruta Dumane, Kristin Hsieh, Ayesha Ali, Orly Morgan, Michael Buckstein, Deborah Marshall

Department of Radiation Oncology Faculty Papers

BACKGROUND: Sexual dysfunction is a significant toxicity of pelvic radiation therapy (RT) for female rectal cancer patients and may be more common with intensity-modulated techniques compared to three-dimensional conformal radiation therapy (3D-CRT). However, limited research has evaluated dose sparing of female sexual organs at risk (OARs), particularly erectile tissues that are critical for sexual function.

PURPOSE: This feasibility study aimed to demonstrate the practicality of contouring and sparing female sexual OARs in rectal cancer RT by generating sexual organ-sparing volumetric modulated arc therapy (SO-VMAT) plans from a small 3D-CRT cohort and comparing dose distributions to guide future planning.

METHODS: Nine …

Exploring Bone Oncology In A Medically Underserved Area: A Retrospective Cohort Of Bone Metastases And Malignant Bone Neoplasia In The Rio Grande Valley, Blake C. Martin, Juan Carlos Lopez Alvarenga, Michael Sander

School of Medicine Publications

Objectives: The Rio Grande Valley (RGV) is a developing clinical research region characterized by its distinctive demographic profile that offers an opportunity to investigate diverse health issues. This pilot investigation sought to evaluate the demographic and clinical characteristics linked to bone metastases and primary malignant bone neoplasms (PMBNs) in patients from the RGV and to compare the frequency of these conditions with the US general population.

Methods: This was a retrospective chart review in which data were gathered from the University of Texas Rio Grande Valley UTHealth electronic database from January 1, 2018 to September 4, 2024. Various statistical analyses …

Monte Carlo Simulations Of Geometric Deformation Of Harrison-Anderson-Mick Applicators Used In Intraoperative Radiation Therapy, Benjamin Insley, Brett Bocian, Sam Beddar, Reza Reiazi, Patrick James Jensen, Rachael M Martin-Paulpeter, Joshua Scott Niedzielski, David Flint, Gabriel Oliveira Sawakuchi, Luis Augusto Perles

Faculty, Staff and Student Publications

Background: The Harrison-Anderson-Mick (HAM) applicator is a high-dose-rate intraoperative radiotherapy (HDR-IORT) applicator used to position Ir-192 brachytherapy sources over surgically-accessed tumor volumes or post-resection tumor beds. Because of the lack of a 3D imaging system, dwell times are optimized pre-surgery by a TG-43-based treatment planning system (TPS) that assumes a perfectly flat applicator surface surrounded by an infinite water phantom. These assumed conditions are disparate from typical treatment conditions, especially in the pelvic regions, which often involve uneven patient surfaces and superficial irradiations with little to no backscatter material.

Purpose: Develop and validate a Monte Carlo (MC) model of HDR-IORT …

Hes V20 Surpasses Galad For Hcc Detection: A Review Of Multi-Dimensional Biomarker Scores And Studies, Fouad Jaber, Hashem B El-Serag

Faculty, Staff and Students Publications

This was a narrative review of select studies published through September of 2024. We review the shift toward multi-dimensional scores such as HCC early detection screening (HES), GALAD, ASAP, and mt-HBT represents a significant advancement in biomarker research for hepatocellular carcinoma (HCC) detection. Unlike single biomarker approaches, these scores integrate various clinical and biochemical factors to enhance predictive accuracy by reflecting different complementary aspects of disease progression and HCC oncogenesis. Proper testing and validation of biomarker scores in phase 3 biomarker studies is essential before wide use can be recommended. We also review the comparative performance of biomarker scores in …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

Faculty, Staff and Students Publications

Background: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

Purpose: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

The Microstructure Of Metastatic Bone Lesions Suggests Tumor Mediated Alterations In Bone Mineralization, Hanwen Fan, Zhan Xu, Carla Berrospe Rodriguez, Noah Dover, Andrei Demkov, Morgan Lilly, Guillermo Aguilar, Larry J Suva, Xiang H-F Zhang, Yuxiao Zhou

Faculty, Staff and Students Publications

Breast, prostate and lung cancer cells frequently metastasize to bone, leading to disruption of the bone microstructure. This study utilized mechanical testing coupled with micro-CT imaging, digital volume correlation (DVC), and atomic force microscopy (AFM) nanomechanical testing to examine the mechanical property variations in mouse long bones (tibia) with metastatic lung cancer cell involvement, spanning from the whole-bone scale to the microstructural level. In addition, we also investigated how metastatic invasion alters the morphology of hydroxyapatite nanocrystals in bone at the nanometer scale. The biochemical composition within metastatic lesions was assessed using Raman spectroscopy and correlated with AFM mechanical testing …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Impact Of Exercise In Patients With Pancreatic Cancer Across Different Treatment Phases: A Systematic Review, Linda Toniolo, Anita Borsati, Cristina Crespo-Garcia, Diana Giannarelli, Christian Ciurnelli, Gloria Adamoli, Lorenzo Belluomini, Ilaria Trestini, Daniela Tregnago, Federico Schena, Robert U. Newton, Salvatore Paiella, Roberto Salvia, Michele Milella, Sara Pilotto, Alice Avancini

Research outputs 2022 to 2026

Background: With a dismal prognosis of 8–10 % 5-year survival since diagnosis, pancreatic cancer remains one of the most aggressive oncological diseases. This work aimed to evaluate the effects of exercise medicine on safety and feasibility, physical fitness, body composition, patient-reported outcomes, and clinical outcomes across different treatment phases in patients with pancreatic cancer. Method: PubMed, Cochrane, and Scopus databases were systematically screened to identify single-arm studies and randomized/non-randomized controlled trials investigating a physical exercise intervention in patients with pancreatic cancer. The RoB 2 and ROBINS-I tools were used to evaluate study quality for randomized and non-randomized studies, respectively. Qualitative …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …