Medical Specialties Commons^™

Accounting For Temporal Variability In Functional Magnetic Resonance Imaging Improves Prediction Of Intelligence, Yang Li, Xin Ma, Raj Sunderraman, Shihao Ji, Suprateek Kundu

Faculty, Staff and Student Publications

Neuroimaging-based prediction methods for intelligence have seen a rapid development. Among different neuroimaging modalities, prediction using functional connectivity (FC) has shown great promise. Most literature has focused on prediction using static FC, with limited investigations on the merits of such analysis compared to prediction using dynamic FC or region-level functional magnetic resonance imaging (fMRI) times series that encode temporal variability. To account for the temporal dynamics in fMRI, we propose a bi-directional long short-term memory (bi-LSTM) approach that incorporates feature selection mechanism. The proposed pipeline is implemented via an efficient algorithm and applied for predicting intelligence using region-level time series …

Multiplatform Analysis Of Intratumoral Pten Heterogeneity In Melanoma, Sharmeen Chagani, Mariana P De Macedo, Fernando Carapeto, Feng Wang, Diego M Marzese, Khalida Wani, Lauren E Haydu, Weiyi Peng, Giang T Ong, Sarah E Warren, Joseph M Beechem, Dave S B Hoon, Gordon B Mills, Michael T Tetzlaff, Alexander J Lazar, Lawrence N Kwong, Michael A Davies

Faculty, Staff and Student Publications

Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies in melanoma. We assessed a unique cohort of eight melanoma samples with focal loss of PTEN protein expression to understand the features and mechanisms of PTEN loss in this disease. We compared the PTEN-negative (PTEN[-]) areas to their adjacent PTEN-positive (PTEN[+]) areas using DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemical platforms. Variations or homozygous deletions of PTEN were identified in PTEN(-) areas that were not detected in the adjacent PTEN(+) …

Bidirectional Association Between Parkinson’S Disease And Obstructive Sleep Apnea: A Cohort Study, Seung-Ho Jeon, Yun Su Hwang, Sun-Young Oh, Byoung-Soo Shin, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Hwan Lee, Hyun Goo Kang, Jong Seung Kim

Faculty, Staff and Student Publications

STUDY OBJECTIVES: Chronic intermittent hypoxia due to obstructive sleep apnea (OSA) causes oxidative stress, which may contribute to the pathophysiology of Parkinson's disease (PD). However, the bidirectional relationship between PD and OSA has not been satisfactorily established. The objective of this study was to try to estimate whether there is a bidirectional relationship between PD and OSA through a retrospective cohort study in the South Korean population.

METHODS: This study used data from the Korean National Health Information Database of the National Health Insurance Service, which contains data from 3.5 million individuals evenly distributed. In study 1, patients with OSA …

Inhibition Of The Interaction Between Hippo/Yap And Akt Signaling With Ursolic Acid And 3’3-Diindolylmethane Suppresses Esophageal Cancer Tumorigenesis, Ruo Yu Meng, Cong Shan Li, Dan Hu, Soon-Gu Kwon, Hua Jin, Ok Hee Chai, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of …

Adagrasib In Advanced Solid Tumors Harboring A Krasg12c Mutation, Tanios S Bekaii-Saab, Rona Yaeger, Alexander I Spira, Meredith S Pelster, Joshua K Sabari, Navid Hafez, Minal Barve, Karen Velastegui, Xiaohong Yan, Aditya Shetty, Hirak Der-Torossian, Shubham Pant

Faculty, Staff and Student Publications

Purpose: Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.

Methods: In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response …

Zranb1 Is An Nbs1 Deubiquitinase And A Potential Target To Overcome Radioresistance And Parp Inhibitor Resistance In Triple-Negative Breast Cancer, Ying Mei, Qinglei Hang, Hongqi Teng, Fan Yao, Mei-Kuang Chen, Mien-Chie Hung, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Inorganic Fertilizer Use And Its Association With Rice Yield Gaps In Sub-Saharan Africa, Jean-Martial Johnson, Ali Ibrahim, Elliott Ronald Dossou-Yovo, Kalimuthu Senthilkumar, Yasuhiro Tsujimoto, Hidetoshi Asai, Kazuki Saito

Faculty, Staff and Student Publications

Where and which countries should receive higher priority for improving inorganic fertilizer use in rice fields in sub-Saharan Africa (SSA)? This study addressed this question by assessing the spatial variation in fertilizer use and its association with rice yield and yield gap in 24 SSA countries through a systematic literature review of peer-reviewed papers, theses, and grey literature published between 1995 and 2021. The results showed a large variation in N, P, and K fertilizer application rates and rice yield and an opportunity for narrowing the yield gap by increasing N and P rates, especially in irrigated rice systems. We …

Low Pitch Significantly Reduces Helical Artifacts In Abdominal Ct, Moiz Ahmad, Peng Sun, Christine B Peterson, Marcus R Anderson, Xinming Liu, Ajaykumar C Morani, Corey T Jensen

Faculty, Staff and Student Publications

Purpose: High helical pitch scanning minimizes scan times in CT imaging, and thus also minimizes motion artifact and mis-synchronization with contrast bolus. However, high pitch produces helical artifacts that may adversely affect diagnostic image quality. This study aims to determine the severity and incidence of helical artifacts in abdominal CT imaging and their relation to the helical pitch scan parameter.

Methods: To obtain a dataset with varying pitch values, we used CT exam data both internal and external to our center. A cohort of 59 consecutive adult patients receiving an abdomen CT examination at our center with an accompanying prior …

Temporal Characterization Of Acute Pain And Toxicity Kinetics During Radiation Therapy For Head And Neck Cancer A Retrospective Study, Vivian Salama, Sara Youssef, Tianlin Xu, Kareem A Wahid, Jaime Chen, Jillian Rigert, Anna Lee, Katherine A Hutcheson, Brandon Gunn, Jack Phan, Adam S Garden, Steven J Frank, William Morrison, Jay P Reddy, Michael T Spiotto, Mohamed A Naser, Cem Dede, Renjie He, Abdallah S R Mohamed, Lisanne V Van Dijk, Ruitao Lin, Carlos J Roldan, David I Rosenthal, Clifton D Fuller, Amy C Moreno, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

OBJECTIVES: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding.

MATERIALS AND METHODS: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUC

RESULTS: …

Stromal-Derived Nrg1 Enables Oncogenic Kras Bypass In Pancreas Cancer, Jincheng Han, Jiaqian Xu, Yonghong Liu, Shaoheng Liang, Kyle A Labella, Deepavali Chakravarti, Denise J Spring, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a …

Atopic Dermatitis And The Risk Of Myocardial Infarction And All-Cause Mortality: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Faculty, Staff and Student Publications

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD.

METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016.

RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was …

Diversity, Equity, And Inclusion In The Melanoma Research Community, Marie E Portuallo, David Y Lu, Gretchen M Alicea, Joel Bolling, Rebecca Lee, Jennifer Mcquade, Allison Betof Warner, Michael Davies, Ashani Weeraratna, Jessie Villanueva, Vito W Rebecca

Faculty, Staff and Student Publications

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant …

The Effects Of Equine-Assisted Activities On Execution Function In Children Aged 7–8 Years: A Randomized Controlled Trial, Xiaodong Cheng, Kexin Zhen, Yongzhao Fan, Qian Tang, Hao Wu

Faculty, Staff and Student Publications

BACKGROUND: This study examines the effects of equine-assisted activity (EAA) training on executive functioning (EF) (inhibitory control, working memory, and cognitive flexibility) in children aged 7-8 years.

METHODS: Twenty-Four healthy children aged 7-8 years with a 1:1 ratio of boys to girls were randomly divided into EAA group (EAAG) or control group (CG). The subjects in EAAG were trained for 12 weeks, and CG participated in normal daily activities. All subjects conducted the Flanker, 1-Back, and More-odd shifting tasks at rest and recorded the average reaction times (RTs) and accuracy data of each task.

RESULTS: After 12 weeks of EAA …

Safety, Efficacy, And Pk/Pd Of Vorasidenib In Previously Treated Patients With Midh1/2 Hematologic Malignancies: A Phase 1 Study, Courtney D Dinardo, Stéphane De Botton, Daniel A Pollyea, Richard M Stone, Jessica K Altman, Amir T Fathi, Tharin Limsakun, Min Liang, Sung Choe, Mohammad Hossain, Adriana E Tron, Qian Meng, Stephanie M Kapsalis, Shuchi S Pandya, Eytan M Stein

Faculty, Staff and Student Publications

No abstract provided.

Obesity And Renal Cell Carcinoma: Biological Mechanisms And Perspectives, Neha Venkatesh, Alberto Martini, Jennifer L Mcquade, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Obesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential "obesity paradox." Clinically, there is uncertainty whether improved outcomes observed after diagnosis are driven by stage, type of treatment received, or artifacts of longitudinal changes in weight and body composition. The biological mechanisms underlying obesity's influence on RCC are not fully established, but multiomic and mechanistic studies suggest an impact on tumor metabolism, particularly …

Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation And Immune Evasion, Kyung-Pil Ko, Yuanjian Huang, Shengzhe Zhang, Gengyi Zou, Bongjun Kim, Jie Zhang, Sohee Jun, Cecilia Martin, Karen J Dunbar, Gizem Efe, Anil K Rustgi, Hiroshi Nakagawa, Jae-Il Park

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.

METHODS: Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion.

RESULTS: We …

Individual Differences In Late Positive Potential Amplitude And Theta Power Predict Cue-Induced Eating, Kyla D Gibney, George Kypriotakis, Francesco Versace

Faculty, Staff and Student Publications

Cue-induced reward-seeking behaviors are regulated by both the affective and cognitive control systems of the brain. This study aimed at investigating how individual differences in affective and cognitive responses to cues predicting food rewards contribute to the regulation of cue-induced eating. We recorded electroencephalogram (EEG) from 59 adults while they viewed emotional and food-related images that preceded the delivery of food rewards (candies) or non-food objects (beads). We measured the amplitude of the late positive potential (LPP) in response to a variety of motivationally relevant images and power in the theta (4-8 Hz) frequency band after candies or beads were …

Long-Term Risks Of Depression And Suicide Among Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Anna Bill-Axelson, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear.

OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort.

DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard …

Clonal Evolution And Hierarchy In Myeloid Malignancies, Koichi Takahashi, Tomoyuki Tanaka

Faculty, Staff and Student Publications

Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the …

Characteristics And Clinical Outcomes Of Patients With Acute Myeloid Leukemia With Inv(3)(Q21q262) Or T(3; 3)(Q21; Q262), Guillaume Richard-Carpentier, Caitlin R Rausch, Koji Sasaki, Danielle Hammond, Kiyomi Morita, Koichi Takahashi, Guilin Tang, Rashmi Kanagal-Shamanna, Kapil Bhalla, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Elizabeth J Shpall, Amin Alousi, Naval G Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission …

T Cell Fate Decisions During Memory Cell Generation With Aging, Ines Sturmlechner, Abhinav Jain, Yunmei Mu, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

The defense against infectious diseases, either through natural immunity or after vaccinations, relies on the generation and maintenance of protective T cell memory. Naïve T cells are at the center of memory T cell generation during primary responses. Upon activation, they undergo a complex, highly regulated differentiation process towards different functional states. Naïve T cells maintained into older age have undergone epigenetic adaptations that influence their fate decisions during differentiation. We review age-sensitive, molecular pathways and gene regulatory networks that bias naïve T cell differentiation towards effector cell generation at the expense of memory and Tfh cells. As a result, …

Safety, Tolerability, And Clinical Activity Of Selinexor In Combination With Pembrolizumab In Treatment Of Metastatic Non-Small Cell Lung Cancer, Mehmet Altan, Janet Tu, Denái R Milton, Bulent Yilmaz, Yanyan Tian, Frank V Fossella, Frank E Mott, George R Blumenschein, Bettzy Stephen, Daniel D Karp, Funda Meric-Bernstam, John V Heymach, Aung Naing

Faculty, Staff and Student Publications

Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC).

Methods: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, …

Vascularized Hepatocellular Carcinoma On A Chip To Control Chemoresistance Through Cirrhosis, Inflammation And Metabolic Activity, Alican Özkan, Danielle L Stolley, Erik N K Cressman, Matthew Mcmillin, Thomas E Yankeelov, Marissa Nichole Rylander

Faculty, Staff and Student Publications

Understanding the effects of inflammation and cirrhosis on the regulation of drug metabolism during the progression of hepatocellular carcinoma (HCC) is critical for developing patient-specific treatment strategies. In this work, we created novel three-dimensional vascularized HCC-on-a-chips (HCCoC), composed of HCC, endothelial, stellate, and Kupffer cells tuned to mimic normal or cirrhotic liver stiffness. HCC inflammation was controlled by tuning Kupffer macrophage numbers, and the impact of cytochrome P450-3A4 (CYP3A4) was investigated by culturing HepG2 HCC cells transfected with CYP3A4 to upregulate expression from baseline. This model allowed for the simulation of chemotherapeutic delivery methods such as intravenous injection and transcatheter …

Evolving Trends And Outcomes In Older Patients With Acute Myeloid Leukemia Including Allogeneic Stem Cell Transplantation, Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Hussein A Abbas, Nicholas J Short, Ghayas Issa, Elias Jabbour, Sherry A Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J Shpall, Richard E Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Identification Of New Aptamer Bc-3 Targeting Rps7 From Rapid Screening For Bladder Carcinoma, Yunyi Liu, Juan Li, Hailong Ou, Dan Qi, Bei Hu, Yuxi Xu, Jian Hu, Yi Xiong, Luling Xia, Jason H Huang, Xiaoxiao Hu, Erxi Wu

Faculty, Staff and Student Publications

Aptamers, short single DNA or RNA oligonucleotides, have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer. However, conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious. Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma, for which there is no specific molecular probe yet. We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells. We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro, in mice, and in patient tumor …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green

Faculty, Staff and Student Publications

The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylatio, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …