Medical Specialties Commons^™

Demographics And Survival In Aml Patients Over 60 Years Of Age. A Single Institutional Analysi, Damilola Gbadebo, Nwabundo Anusim, Ishmael Jaiyesimi

Posters

Acute Myeloid Leukemia (AML) is a malignancy of the myeloid cell line. Patients diagnosed with AML, typically exhibit symptoms of neutropenia, anemia and thrombocytopenia. The diagnosis of AML is based on greater than 20 percent of myeloid cells in the bone marrow (1). Some risk factors for acquiring the disease include, but not limited to age, sex, smoking, exposure to certain chemicals, radiation, genetic predisposition and being treated with certain chemotherapeutic agents (2).
AML is frequently diagnosed among people between ages 65-74, with a current relative survival rate for AML being 28.7%. Men account for majority of these cases, at …

Tumor Locations Impact On Cardiac Toxicity In Women That Received Partial Breast Irradiation, Sara Diltz, Muayad Almahariq, Joshua Dilworth

Posters

Accelerated partial breast irradiation (APBI) is an appropriate modality for select women with low-risk breast cancer. While APBI delivers radiation dose to a smaller volume of breast tissue compared to whole breast irradiation, dose to the heart and coronary vessels may be relatively high, depending on the proximity of the treatment device to these structures. The primary goal of this study is to determine if the risk of adverse cardiac events depends on tumor location in women receiving APBI.

High Dose Rate Brachytherapy Monotherapy Versus External Beam Radiotherapy With Hdr Brachytherapy Boost For Unfavorable Intermediate Prostate Cancer Patients, Doyle Lang, Benjamin Willen, Daniel J. Krauss, Sirisha R. Nandalur

Posters

Prostate cancer is the most common male malignancy by incidence in the world. Treatment differs by the patient’s risk stratification. For the treatment of unfavorable intermediate-risk prostate cancer, external beam radiotherapy with high-dose-rate brachytherapy boost was the accepted treatment but high-dose-rate brachytherapy as monotherapy has been proposed as a potentially viable treatment option. External beam radiotherapy treatment involves shooting high-energy photons or particle radiation through normal healthy tissue to hit the tumor directly. High-dose-rate brachytherapy involves inserting radioactive seeds into the tumor. Studies are needed to compare toxicity profiles and relative outcomes between the two treatment options.

Examining Ndufab1 Expression In Head And Neck Squamous Cell Carcinoma, Addison L. Stevens

Honors Theses

Head and neck squamous cell carcinoma (HNSCC) accounts for around 4% of all cancers in the USA. HNSCC includes cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Reprogramming of mitochondrial metabolism has been known to promote oncogenesis. NDUFAB1, a nuclear encoded subunit of respiratory complex I (RCI) in the inner mitochondrial membrane, is abundantly expressed at the mRNA level in HNSCC patients. Based on this finding, we hypothesize that NDUFAB1 protein expression is high in HNSCC and that NDUFAB1 expression predicts a poor prognosis in HNSCC patients. We determined NDUFAB1 expression in HNSCC using immunohistochemistry and pathology guided …

An Oncology, Lifestyle Medicine, And Cardiac Rehabilitation Partnership In The Development Of A Group Medical Visit Model For Cancer Survivors, Amy Litterini, Caitlin Coppenrath, Ashley Speckhart, Amy Pearl, Theodore Wissink

Costas T. Lambrew Research Retreat 2023

Methods/Approach: An oncology and cardiology team developed an oncology provider survey in REDCap designed to assess attitudes regarding perspectives on cardio-oncology, rehabilitation, and Lifestyle Medicine. The 27-item multiple choice and Likert-style survey was distributed via email on three separate occasions to MaineHealth Cancer Care Network providers (n=66) in spring, 2022.

The Past, Present, And Future Of Distress Screening: Launching A Robust Distress Screening Program At A Large Outpatient Medical Oncology Practice Serving Rural/Underserved Communities, Kevin Stein, Trisha Warren-Vanhorn, Meredith Curtis, Amy Litterini, Amit Sanyal

Costas T. Lambrew Research Retreat 2023

After redesign, administration of the DT at initial chemotherapy teaching sessions and robust searchable databases integrated with EHR systems, allowing providers/researchers to create reports filtered by date ranges, encounter type, clinical site/facility, scores of ≥4, domain (physical, emotional, practical), and outcome (referral to specialist)

Mincle-Gsdmd-Mediated Release Of Il-1Β Small Extracellular Vesicles From Hepatic Macrophages In Ethanol-Induced Liver Injury, Quanri Zhang, Weiwei Liu, Katarzyna Bulek, Han Wang, Megan R Mcmullen, Xiaoqin Wu, Nicole Welch, Renliang Zhang, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy, Xiaoxia Li

Faculty, Staff and Student Publications

BACKGROUND: Macrophage-inducible C-type lectin (Mincle) is expressed on hepatic macrophages and senses ethanol (EtOH)-induced danger signals released from dying hepatocytes and promotes IL-1β production. However, it remains unclear what and how EtOH-induced Mincle ligands activate downstream signaling events to mediate IL-1β release and contribute to alcohol-associated liver disease (ALD). In this study, we investigated the association of circulating β-glucosylceramide (β-GluCer), an endogenous Mincle ligand, with severity of ALD and examined the mechanism by which β-GluCer engages Mincle on hepatic macrophages to release IL-1β in the absence of cell death and exacerbates ALD.

METHOD AND RESULTS: Concentrations of β-GluCer were increased …

Fully Human Monoclonal Antibody Targeting Activated Adam10 On Colorectal Cancer Cells, Nayanendu Saha, Du-San Baek, Rachelle P Mendoza, Dorothea Robev, Yan Xu, Yehuda Goldgur, M Jason De La Cruz, Elisa De Stanchina, Peter W Janes, Kai Xu, Dimiter S Dimitrov, Dimitar B Nikolov

Faculty, Staff and Student Publications

Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initiated upon Notch cleavage by the metalloprotease ADAM10. It has been shown that ADAM10 overexpression correlates with aberrant signaling from Notch, erbBs, and other receptors, as well as a more aggressive metastatic phenotype, in a range of cancers including colon, gastric, prostate, breast, ovarian, uterine, and leukemia. ADAM10 inhibition, therefore, stands out as an important and new approach to deter the progression of advanced CRC. For targeting the ADAM10 substrate-binding region, which is located …

Efficacy Of Alternative Dose Regimens Of Exemestane In Postmenopausal Women With Stage 0 To Ii Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial, Davide Serrano, Sara Gandini, Parjhitham Thomas, Katherine D Crew, Nagi B Kumar, Lana A Vornik, J Jack Lee, Paolo Veronesi, Giuseppe Viale, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Harriet Johansson, Mauro D'Amico, Flavio Guasone, Stefano Spinaci, Bjørn-Erik Bertelsen, Gunnar Mellgren, Isabelle Bedrosian, Diane Weber, Tawana Castile, Eileen Dimond, Brandy M Heckman-Stoddard, Eva Szabo, Powel H Brown, Andrea Decensi, Bernardo Bonanni

Faculty, Staff and Student Publications

IMPORTANCE: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events.

OBJECTIVE: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer …

Advances In The Treatment Of Invasive Fungal Disease, Zhuan Zhang, Gerald F Bills, Zhiqiang An

Faculty, Staff and Student Publications

With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of …

Comparison Of Reconstructed Prompt Gamma Emissions Using Maximum Likelihood Estimation And Origin Ensemble Algorithms For A Compton Camera System Tailored To Proton Range Monitoring, Ingrid Valencia Lozano, George Dedes, Steve Peterson, Dennis Mackin, Andreas Zoglauer, Sam Beddar, Stephen Avery, Jerimy Polf, Katia Parodi

Faculty, Staff and Student Publications

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit …

Outcomes Of The “Brca Quality Improvement Dissemination Program”: An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems, Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …

A Protocol For A Cluster Randomized Trial Of Care Delivery Models To Improve The Quality Of Smoking Cessation And Shared Decision Making For Lung Cancer Screening, Lisa M Lowenstein, Ya-Chen Tina Shih, Jennifer Minnix, Maria A Lopez-Olivo, Kristin G Maki, George Kypriotakis, Viola B Leal, Sanjay S Shete, James Fox, Shawn P Nishi, Paul M Cinciripini, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: Patients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening.

METHODS: We will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be …

P53 And Ovarian Carcinoma Survival: An Ovarian Tumor Tissue Analysis Consortium Study, Martin Köbel, Eun-Young Kang, Ashley Weir, Peter F Rambau, Cheng-Han Lee, Gregg S Nelson, Prafull Ghatage, Nicola S Meagher, Marjorie J Riggan, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Christiani Bisinotto, Michelle Boisen, Jessica Boros, Alison H Brand, Angela Brooks-Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney-Brooks, Kara L Cushing-Haugen, Cezary Cybulski, Suha Deen, Mona A El-Bahrawy, Esther Elishaev, Ramona Erber, Sian Fereday, Aocs Group, Anna Fischer, Simon A Gayther, Arantzazu Barquin-Garcia, Aleksandra Gentry-Maharaj, C Blake Gilks, Helena Gronwald, Marcel Grube, Paul R Harnett, Holly R Harris, Andreas D Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez-Linan, Michael E Jones, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A Longacre, Maria Lycke, Constantina Mateoiu, Bryan M Mccauley, Valerie Mcguire, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Paz-Ares, Teresa Ramón Y Cajal, Joseph H Rothstein, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, Helen Steed, Sarah J Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S Whittemore, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido Dos Reis, Ian Campbell, Linda S Cook, Anna Defazio, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Marc T Goodman, Ellen L Goode, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Stefan Kommoss, Nhu D Le, Stewart G Martin, Usha Menon, Francesmary Modugno, Paul Dp Pharoah, Joellen M Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Susan J Ramus, James D Brenton

Faculty, Staff and Student Publications

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were …

Combining Physics-Based Models With Deep Learning Image Synthesis And Uncertainty In Intraoperative Cone-Beam Ct Of The Brain, Xiaoxuan Zhang, Alejandro Sisniega, Wojciech B Zbijewski, Junghoon Lee, Craig K Jones, Pengwei Wu, Runze Han, Ali Uneri, Prasad Vagdargi, Patrick A Helm, Mark Luciano, William S Anderson, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention.

PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality.

METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network …

Cone-Beam Ct Sampling Incompleteness: Analytical And Empirical Studies Of Emerging Systems And Source-Detector Orbits, Pengwei Wu, Aina Tersol, Rolf Clackdoyle, John M Boone, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

PURPOSE: Motivated by emerging cone-beam computed tomography (CBCT) systems and scan orbits, we aim to quantitatively assess the completeness of data for 3D image reconstruction-in turn, related to "cone-beam artifacts." Fundamental principles of cone-beam sampling incompleteness are considered with respect to an analytical figure-of-merit [FOM, denoted

APPROACH:A previously proposed analytical FOM [tan ( ψmin ) , defined as the minimum angle between a point in the 3D image reconstruction and the x-ray source over the scan orbit] was analyzed for a variety of CBCT geometries. A physical test phantom was configured with parallel disk pairs (perpendicular to the z-axis) …

High-Dose Once-Daily Thoracic Radiotherapy In Limited-Stage Small-Cell Lung Cancer: Calgb 30610 (Alliance)/Rtog 0538, Jeffrey Bogart, Xiaofei Wang, Gregory Masters, Junheng Gao, Ritsuko Komaki, Laurie E Gaspar, John Heymach, James Bonner, Charles Kuzma, Saiama Waqar, William Petty, Thomas E Stinchcombe, Jeffrey D Bradley, Everett Vokes

Faculty, Staff and Student Publications

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.

METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity …

National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im

Faculty, Staff and Student Publications

Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision …

Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe

Faculty, Staff and Student Publications

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …

Combining Mendelian Randomization And Network Deconvolution For Inference Of Causal Networks With Gwas Summary Data, Zhaotong Lin, Haoran Xue, Wei Pan

Faculty, Staff and Student Publications

Mendelian randomization (MR) has been increasingly applied for causal inference with observational data by using genetic variants as instrumental variables (IVs). However, the current practice of MR has been largely restricted to investigating the total causal effect between two traits, while it would be useful to infer the direct causal effect between any two of many traits (by accounting for indirect or mediating effects through other traits). For this purpose we propose a two-step approach: we first apply an extended MR method to infer (i.e. both estimate and test) a causal network of total effects among multiple traits, then we …

Philadelphia-Like Genetic Rearrangements In Adults With B-Cell All: Refractoriness To Chemotherapy And Response To Tyrosine Kinase Inhibitor In Abl Class Rearrangements, Jayastu Senapati, Elias Jabbour, Marina Konopleva, Nicholas J Short, Guilin Tang, Naval Daver, Partow Kebriaei, Tapan Kadia, Naveen Pemmaraju, Koichi Takahashi, Courtney Dinardo, Koji Sasaki, Gautam Borthakur, Beenu Thakral, Rashmi Kanagal-Shamanna, Keyur Patel, Farhad Ravandi, Kathryn Roberts, Charles Mullighan, Hagop Kantarjian, Nitin Jain

Faculty, Staff and Student Publications

PURPOSE: Philadelphia-like (Ph-like) B-cell ALL is a high-risk subtype of B-cell ALL that shares a gene expression profile with Ph-positive ALL, but without a

PATIENTS AND METHODS: We performed a retrospective review of patients with B-cell ALL treated at MD Anderson Cancer Center to identify recurrent genetic fusions commonly seen in Ph-like ALL and focus on patients treated with TKI.

RESULTS: We identified 23 patients with recurrent genetic fusions commonly seen in Ph-like ALL; 14 had

CONCLUSION: Understanding the genomics of B-cell ALL is important for disease prognostication and for precise treatment planning. Besides conventional cytogenetics and directed FISH testing, …

Critical Role Of The Ventral Temporal Lobe In Naming, Kathryn M Snyder, Kiefer J Forseth, Cristian Donos, Patrick S Rollo, Simon Fischer-Baum, Joshua Breier, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia.

METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and …

Aapm Task Group Report 305: Guidance For Standardization Of Vendor-Neutral Reject Analysis In Radiography, Kevin Little, Ingrid Reiser, Bruce Apgar, Poonam Dalal, Jaydev Dave, Ryan Fisher, Katie Hulme, Mary Ellen Jafari, Emily Marshall, Stephen Meyer, Quentin Moore, Nicole Murphy, Thomas Nishino, Katelyn Nye, Kevin O'Donnell, John Sabol, Adrian Sanchez, William Sensakovic, Lawrence Tarbox, Robert Uzenoff, Alisa Walz-Flannigan, Charles Willis, Jie Zhang

Faculty, Staff and Student Publications

Reject rate analysis is considered an integral part of a diagnostic radiography quality control (QC) program. A rejected image is a patient radiograph that was not presented to a radiologist for diagnosis and that contributes unnecessary radiation dose to the patient. Reject rates that are either too high or too low may suggest systemic department shortcomings in QC mechanisms. Due to the lack of standardization, reject data often cannot be easily compared between radiography systems from different vendors. The purpose of this report is to provide guidance to help standardize data elements that are required for comprehensive reject analysis and …

Phase I Trial Of Autologous Rna-Electroporated Cmet-Directed Car T Cells Administered Intravenously In Patients With Melanoma And Breast Carcinoma, Payal D Shah, Alexander C Huang, Xiaowei Xu, Robert Orlowski, Ravi K Amaravadi, Lynn M Schuchter, Paul Zhang, Julia Tchou, Tina Matlawski, Amanda Cervini, Joanne Shea, Joan Gilmore, Lester Lledo, Karen Dengel, Amy Marshall, E John Wherry, Gerald P Linette, Andrea Brennan, Vanessa Gonzalez, Irina Kulikovskaya, Simon F Lacey, Gabriela Plesa, Carl H June, Robert H Vonderheide, Tara C Mitchell

Faculty, Staff and Student Publications

PURPOSE: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET.

EXPERIMENTAL DESIGN: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated.

RESULTS: Mean age was …

Prospective Study Of Perioperative Circulating Tumor Dna Dynamics In Patients Undergoing Hepatectomy For Colorectal Liver Metastases, Timothy E Newhook, Michael J Overman, Yun Shin Chun, Arvind Dasari, Ching-Wei D Tzeng, Hop S Tran Cao, Victoria Raymond, Christine Parseghian, Benny Johnson, Yujiro Nishioka, Yoshikuni Kawaguchi, Abhineet Uppal, Timothy J Vreeland, Ariel Jaimovich, Elsa M Arvide, Jenilette V Cristo, Steven H Wei, Kanwal P Raghav, Van K Morris, Jeffrey E Lee, Scott Kopetz, Jean-Nicolas Vauthey

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.

SUMMARY BACKGROUND DATA: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.

METHODS: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.

RESULTS: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but …

National Brain Tumour Registry Of China (Nbtrc) Statistical Report Of Primary Brain Tumours Diagnosed In China In Years 2019–2020, Dan Xiao, Changxiang Yan, Deling Li, Tianshu Xi, Xianzhi Liu, Dan Zhu, Guodong Huang, Jianguo Xu, Zhengwen He, Anhua Wu, Chiyuan Ma, Jiang Long, Kai Shu, Hongming Ji, Ning Wang, Gang Chen, Jiankai Yang, Hui Ma, Zhiyong Li, Xiaochuan Sun, Yan Qu, Zhixiong Liu, Xiaofan Jiang, Chunlei Tian, Shilei Ni, Renya Zhan, Liwen Chen, Ming Ge, Maode Wang, Xiaobing Jiang, Geng Guo, Zhenmin Han, Chuan Zhang, Tingrong Zhang, Changwu Dou, Liangzhao Chu, Pengcheng Wang, Junfei Shao, Xiyue Wu, Ju Yu, Yu Wang, Nan Wu, Rui Zhang, Mingming Zhang, Yong Hong, Jianzhong Gao, Yunqian Li, Yawen Pan, Bing Zhao, Nan Ji, Guangliang Shan, Chirag B Patel, Wang Jia, Liwei Zhang

Faculty, Staff and Student Publications

BACKGROUND: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed.

METHODS: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). …

Neural Network Based Ensemble Model To Predict Radiation Induced Lymphopenia After Concurrent Chemo-Radiotherapy For Non-Small Cell Lung Cancer From Two Institutions, Yejin Kim, Ibrahim Chamseddine, Yeona Cho, Jin Sung Kim, Radhe Mohan, Nadya Shusharina, Harald Paganetti, Steven Lin, Hong In Yoon, Seungryong Cho, Clemens Grassberger

Faculty, Staff and Student Publications

The use of adjuvant Immune Checkpoint Inhibitors (ICI) after concurrent chemo-radiation therapy (CCRT) has become the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, prolonged radiotherapy regimens are known to cause radiation-induced lymphopenia (RIL), a long-neglected toxicity that has been shown to correlate with response to ICIs and survival of patients treated with adjuvant ICI after CCRT. In this study, we aim to develop a novel neural network (NN) approach that integrates patient characteristics, treatment related variables, and differential dose volume histograms (dDVH) of lung and heart to predict the incidence of RIL at the end …

Artificial Intelligence In Continuous Kidney Replacement Therapy, Lucas J. Liu, Tomonori Takeuchi, Jin Chen, Javier A. Neyra

Markey Cancer Center Faculty Publications

Over the past decade, artificial intelligence (AI) through machine learning (ML) has been increasingly used in health care applications. The use of AI/ML to enhance the provision of continuous kidney replacement therapy (CKRT) is an area of active investigation because of the growing clinical needs of critically ill patients and the abundance of multimodal data from the electronic health records (EHRs) and the CKRT machine itself. Importantly, best clinical practices of CKRT have not been sufficiently standardized, so there is considerable heterogeneity in utilization and deliverables. In this context, AI/ML-based tools could facilitate informed decisions to enhance CKRT goal-oriented deliver- …

Development And Characterization Of Nanobodies That Specifically Target The Oncogenic Phosphatase Of Regenerating Liver-3 (Prl-3) And Impact Its Interaction With A Known Binding Partner, Cnnm3, Caroline N. Smith, Kyle Kihn, Zachary A. Williamson, K. Martin Chow, Louis B. Hersh, Konstantin V. Korotkov, Daniel Deredge, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3’s oncogenic functions are not well under- stood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobo- dies, targeting PRL-3 with a KD of 30–300 nM and no activity towards highly homologous family members PRL-1 and PRL-2. We found that longer and charged N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide …

Icam-1-Supar-Cd11b Axis Is A Novel Therapeutic Target For Metastatic Triple-Negative Breast Cancer, Dong Li, Hami Hemati, Younhee Park, Rokana Taftaf, Youbin Zhang, Jinpeng Liu, Massimo Cristofanilli, Xia Liu

Markey Cancer Center Faculty Publications

Accumulating evidence demonstrates that circulating tumor cell (CTC) clusters have higher metastatic ability than single CTCs and negatively correlate with cancer patient outcomes. Along with homotypic CTC clusters, heterotypic CTC clusters (such as neutrophil–CTC clusters), which have been identified in both cancer mouse models and cancer patients, lead to more efficient metastasis formation and worse patient outcomes. However, the mechanism by which neutrophils bind to CTCs remains elusive. In this study, we found that intercellular adhesion molecule-1 (ICAM-1) on triple- negative breast cancer (TNBC) cells and CD11b on neutrophils mediate tumor cell–neutrophil binding. Consequently, CD11b deficiency inhibited tumor cell–neutrophil binding …