Biomedical Informatics Commons^™

Swallowing After Primary Tors And Unilateral Or Bilateral Radiation For Low- To Intermediate-Risk Tonsil Cancer, Carly E A Barbon, Christopher M K Yao, Christine B Peterson, Amy C Moreno, Ryan P Goepfert, Faye M Johnson, Gregory M Chronowski, Clifton D Fuller, Neil D Gross, Katherine A Hutcheson

Faculty, Staff and Student Publications

Objective: The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT).

Study design: Secondary analysis of prospective cohort.

Setting: Single institution.

Methods: The study …

Membrane-Anchored And Tumor-Targeted Il12 (Attil12)-Pbmc Therapy For Osteosarcoma, Qing Yang, Jiemiao Hu, Zhiliang Jia, Qi Wang, Jing Wang, Long Hoang Dao, Wendong Zhang, Sheng Zhang, Xueqing Xia, Richard Gorlick, Shulin Li

Faculty, Staff and Student Publications

Purpose: Chimeric antigen receptor (CAR) T-cell therapy has shown great promise for treating hematologic malignancies but requires a long duration of T-cell expansion, is associated with severe toxicity, and has limited efficacy for treating solid tumors. We designed experiments to address those challenges.

Experimental design: We generated a cell membrane-anchored and tumor-targeted IL12 (attIL12) to arm peripheral blood mononuclear cells (PBMC) instead of T cells to omit the expansion phase for required CAR T cells.

Results: This IL12-based attIL12-PBMC therapy showed significant antitumor efficacy in both heterogeneous osteosarcoma patient-derived xenograft tumors and metastatic osteosarcoma tumors with no observable toxic effects. …

Multidisciplinary Management Of Spinal Metastases: What The Radiologist Needs To Know, Sarah M Bahouth, Debra N Yeboa, Amol J Ghia, Claudio E Tatsui, Christopher A Alvarez-Breckenridge, Thomas H Beckham, Andrew J Bishio, Jing Li, Mary Frances Mcaleer, Robert Y North, Laurence D Rhines, Todd A Swanson, Wang Chenyang, Behrang Amini

Faculty, Staff and Student Publications

The modern management of spinal metastases requires a multidisciplinary approach that includes radiation oncologists, surgeons, medical oncologists, and diagnostic and interventional radiologists. The diagnostic radiologist can play an important role in the multidisciplinary team and help guide assessment of disease and selection of appropriate therapy. The assessment of spine metastases is best performed on MRI, but imaging from other modalities is often needed. We provide a review of the clinical and imaging features that are needed by the multidisciplinary team caring for patients with spine metastases and stress the importance of the spine radiologist taking responsibility for synthesizing imaging features …

Estrogen-Related Receptor Alpha Is An Ampk-Regulated Factor That Promotes Ischemic Muscle Revascularization And Recovery In Diet-Induced Obese Mice, Danesh H Sopariwala, Andrea S Rios, Mi Kyung Park, Min Sup Song, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Obesity and type II diabetes are leading causes of peripheral arterial disease (PAD), which is characterized by vascular insufficiency and ischemic damage in the limb skeletal muscle. Glycemic control is not sufficient to prevent progression of PAD, and molecular targets that can promote muscle neo-angiogenesis in obesity and diabetes remain poorly defined. Here, we have investigated whether nuclear receptor estrogen-related receptor alpha (ERRα) can promote ischemic revascularization in the skeletal muscles of diet-induced obese (DIO) mice. Using muscle-specific ERRα transgenic mice, we found that ERRα overexpression promotes revascularization, marked by increased capillary staining and muscle perfusion in DIO mice after …

Aapm Medical Physics Practice Guideline 5b: Commissioning And Qa Of Treatment Planning Dose Calculations-Megavoltage Photon And Electron Beams, Mark W Geurts, Dustin J Jacqmin, Lindsay E Jones, Stephen F Kry, Dimitris N Mihailidis, Jared D Ohrt, Timothy Ritter, Jennifer B Smilowitz, Nicholai E Wingreen

Faculty, Staff and Student Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth …

Severe Radiation-Induced Lymphopenia Attenuates The Benefit Of Durvalumab After Concurrent Chemoradiotherapy For Nsclc, Wang Jing, Ting Xu, Lirong Wu, Pablo B Lopez, Clemens Grassberger, Susannah G Ellsworth, Radhe Mohan, Brian P Hobbs, George R Blumenschein, Janet Tu, Mehmet Altan, Percy Lee, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

Introduction: Durvalumab after concurrent chemoradiation (CCRT) for NSCLC improves survival, but only in a subset of patients. We investigated the effect of severe radiation-induced lymphopenia (sRIL) on survival in these patients.

Methods: Outcomes after CCRT (2010-2019) or CCRT followed by durvalumab (2018-2019) were reviewed. RIL was defined by absolute lymphocyte count (ALC) nadir in samples collected at end of CCRT; sRIL was defined as nadir ALC less than 0.23 × 109/L (the lowest tertile). Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Cox proportional hazard modeling evaluated associations between clinical variables and survival.

Results: Of …

Repeatability And Reproducibility Assessment Of The Apparent Diffusion Coefficient In The Prostate: A Trial Of The Ecog-Acrin Research Group (Acrin 6701), Michael A Boss, Bradley S Snyder, Eunhee Kim, Dena Flamini, Sarah Englander, Karthik M Sundaram, Naveen Gumpeni, Suzanne L Palmer, Haesun Choi, Adam T Froemming, Thorsten Persigehl, Matthew S Davenport, Dariya Malyarenko, Thomas L Chenevert, Mark A Rosen

Faculty, Staff and Student Publications

Background: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.

Purpose: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting.

Study type: Prospective multi-institutional.

Subjects: Twenty-nine males, ages 53 to 80 (median 63) …

Patient-Reported Bowel And Urinary Function In Long-Term Survivors Of Squamous Cell Carcinoma Of The Anus Treated With Definitive Intensity Modulated Radiation Therapy And Concurrent Chemotherapy, Brian De, Kelsey L Corrigan, Michael K Rooney, Ethan B Ludmir, Prajnan Das, Grace L Smith, Cullen M Taniguchi, Bruce D Minsky, Eugene J Koay, Albert Koong, Van K Morris, Craig A Messick, Y Nancy You, George J Chang, O Lenaine Westney, Graciela M Nogueras Gonzalez, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs).

Methods and materials: We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). …

Lif-Ting Ferroptosis To Improve Liver Cancer Therapy, Fan Yao, Yang Zhao, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Pure Erythroid Leukemia Is Characterized By Biallelic Tp53 Inactivation And Abnormal P53 Expression Patterns In De Novo And Secondary Cases, Hong Fang, Sa A Wang, Joseph D Khoury, Siba El Hussein, Do Hwan Kim, Mehrnoosh Tashakori, Zhenya Tang, Shaoying Li, Zhihong Hu, Fatima Zahra Jelloul, Keyur P Patel, Timothy J Mcdonnell, Tapan Kadia, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

International Expert Consensus On Immunotherapy For Early-Stage Non-Small Cell Lung Cancer, Wenhua Liang, Kaican Cai, Qingdong Cao, Chun Chen, Haiquan Chen, Jun Chen, Ke-Neng Chen, Qixun Chen, Tianqing Chu, Yuchao Dong, Jiang Fan, Wentao Fang, Junke Fu, Xiangning Fu, Shugeng Gao, Di Ge, Guojun Geng, Qing Geng, Jie He, Jian Hu, Jie Hu, Wei-Dong Hu, Feng Jiang, Tao Jiang, Wenjie Jiao, He-Cheng Li, Qiang Li, Shanqing Li, Shuben Li, Xiangnan Li, Yong-De Liao, Changhong Liu, Hongxu Liu, Yang Liu, Zhuming Lu, Qingquan Luo, Haitao Ma, Xiaojie Pan, Guibin Qiao, Shengxiang Ren, Weiyu Shen, Yong Song, Daqiang Sun, Guangsuo Wang, Jie Wang, Mengzhao Wang, Qiwen Wang, Wen-Xiang Wang, Li Wei, Ming Wu, Nan Wu, Hui Xia, Shi-Dong Xu, Fan Yang, Kang Yang, Yue Yang, Fenglei Yu, Zhen-Tao Yu, Dong-Sheng Yue, Lanjun Zhang, Weidong Zhang, Zhenfa Zhang, Guofang Zhao, Jian Zhao, Xiaojing Zhao, Chengzhi Zhou, Qinghua Zhou, Kunshou Zhu, Yuming Zhu, Toyoaki Hida, Wolfram C M Dempke, Antonio Rossi, Marc De Perrot, Robert A Ramirez, Mariano Provencio, Jay M Lee, Antonio Passaro, Lorenzo Spaggiari, Jonathan Spicer, Nicolas Girard, Patrick M Forde, Tony S K Mok, Tina Cascone, Jianxing He

Faculty, Staff and Student Publications

No abstract provided.

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

Cisplatin And Gemcitabine Exert Opposite Effects On Immunotherapy With Pd-1 Antibody In K-Ras-Driven Cancer, Christophe Glorieux, Xiaojun Xia, Xin You, Zining Wang, Yi Han, Jing Yang, Gauthier Noppe, Christophe De Meester, Jianhua Ling, Annie Robert, Hui Zhang, Sheng-Ping Li, Huamin Wang, Paul J Chiao, Li Zhang, Xiaobing Li, Peng Huang

Faculty, Staff and Student Publications

INTRODUCTION: Immunochemotherapy using PD-1/PD-L1 antibodies in combination with chemotherapeutic agents has become a mainstream treatment for cancer patients, but it remains unclear which drug combinations would produce best therapeutic outcome.

OBJECTIVES: The purpose of this study was to investigate two common chemotherapeutic drugs, gemcitabine and cisplatin, for their impacts on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers known to overexpress PD-L1.

METHODS: Both in vitro assays and syngeneic mouse tumor models were used in this study. Biochemical and molecular assays were used to determine the effects of drugs on T cell functions in cell culture models and in …

A Decade's Experience In Pediatric Chromosomal Microarray Reveals Distinct Characteristics Across Ordering Specialties, Mariam T Mathew, Austin Antoniou, Naveen Ramesh, Min Hu, Jeffrey Gaither, Danielle Mouhlas, Sayaka Hashimoto, Maggie Humphrey, Theodora Matthews, Jesse M Hunter, Shalini Reshmi, Matthew Schultz, Kristy Lee, Ruthann Pfau, Catherine Cottrell, Kim L Mcbride, Nicholas E Navin, Bimal P Chaudhari, Marco L Leung

Faculty, Staff and Student Publications

Chromosomal microarray (CMA) is a testing modality frequently used in pediatric patients; however, published data on its utilization are limited to the genetic setting. We performed a database search for all CMA testing performed from 2010 to 2020, and delineated the diagnostic yield based on patient characteristics, including sex, age, clinical specialty of providers, indication of testing, and pathogenic finding. The indications for testing were further categorized into Human Phenotype Ontology categories for analysis. This study included a cohort of 14,541 patients from 29 different medical specialties, of whom 30% were from the genetics clinic. The clinical indications for testing …

Car Treg Cells: Prime Suspects In Therapeutic Resistance, Neeraj Saini, Sattva S Neelapu

Faculty, Staff and Student Publications

Using comprehensive single-cell profiling, two studies reveal the molecular phenotypes of CAR T cells associated with durable response in patients with lymphoma, and highlight the role of CAR regulatory T cells in mediating resistance.

Quantifying The Risk And Dosimetric Variables Of Symptomatic Brainstem Injury After Proton Beam Radiation In Pediatric Brain Tumors, Rituraj Upadhyay, Kaiping Liao, David R Grosshans, Susan L Mcgovern, Mary Frances Mcaleer, Wafik Zaky, Murali M Chintagumpala, Anita Mahajan, Debra Nana Yeboa, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT.

Methods: All patients < 21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem.

Results: A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT …

Tumor Immune Contexture Is A Determinant Of Anti-Cd19 Car T Cell Efficacy In Large B Cell Lymphoma, Nathalie Scholler, Regis Perbost, Frederick L Locke, Michael D Jain, Sarah Turcan, Corinne Danan, Edmund C Chang, Sattva S Neelapu, David B Miklos, Caron A Jacobson, Lazaros J Lekakis, Yi Lin, Armin Ghobadi, Jenny J Kim, Justin Chou, Vicki Plaks, Zixing Wang, Allen Xue, Mike Mattie, John M Rossi, Adrian Bot, Jérôme Galon

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell …

Oligometastatic Disease In The Liver: The Role Of Interventional Oncology, Ather Adnan, Rahul Anil Sheth, Alda Tam

Faculty, Staff and Student Publications

Oligometastatic disease represents a clinically discrete intermediate stage of cancer progression and is an expanding area of research. While surgical metastatectomy has been recognized for decades as an effective treatment option in select patients, options for metastasis-directed therapy have broadened in scope with advancements in the armamentarium of non- and minimally invasive modalities. Recent preclinical studies investigating the immunology surrounding liver metastases demonstrate treatment resistance to immunotherapy in affected patients and show how locoregional therapy has the ability to overcome this resistance. In this paper, we review advancements in our understanding of oligometastatic disease, metastasis-directed therapy, effect of liver metastasis …

An Empirical Model Of Proton Rbe Based On The Linear Correlation Between X-Ray And Proton Radiosensitivity, David B Flint, Chase E Ruff, Scott J Bright, Pablo Yepes, Qianxia Wang, Mandira Manandhar, Mariam Ben Kacem, Broderick X Turner, David K J Martinus, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Background: Proton relative biological effectiveness (RBE) is known to depend on physical factors of the proton beam, such as its linear energy transfer (LET), as well as on cell-line specific biological factors, such as their ability to repair DNA damage. However, in a clinical setting, proton RBE is still considered to have a fixed value of 1.1 despite the existence of several empirical models that can predict proton RBE based on how a cell's survival curve (linear-quadratic model [LQM]) parameters α and β vary with the LET of the proton beam. Part of the hesitation to incorporate variable RBE models …

Lmo2 Expression Is Frequent In T-Lymphoblastic Leukemia And Correlates With Survival, Regardless Of T-Cell Stage, Kerri-Ann Latchmansingh, Xiaoqiong Wang, Ramiro E Verdun, Mario L Marques-Piubelli, Francisco Vega, M James You, Jennifer Chapman, Izidore S Lossos

Faculty, Staff and Student Publications

T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 …

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy.

Results: The …

An Interdisciplinary Consensus On The Management Of Brain Metastases In Patients With Renal Cell Carcinoma, Elshad Hasanov, Debra Nana Yeboa, Mathew D Tucker, Todd A Swanson, Thomas Hendrix Beckham, Brian Rini, Chibawanye I Ene, Merve Hasanov, Sophie Derks, Marion Smits, Shaan Dudani, Daniel Y C Heng, Priscilla K Brastianos, Axel Bex, Sahin Hanalioglu, Jeffrey S Weinberg, Laure Hirsch, Maria I Carlo, Ayal Aizer, Paul David Brown, Mehmet Asim Bilen, Eric Lin Chang, Jerry Jaboin, James Brugarolas, Toni K Choueiri, Michael B Atkins, Bradley A Mcgregor, Lia M Halasz, Toral R Patel, Scott G Soltys, David F Mcdermott, James Bradley Elder, Mustafa K Baskaya, James B Yu, Robert Timmerman, Michelle Miran Kim, Melike Mut, James Markert, Kathryn Beal, Nizar M Tannir, George Samandouras, Frederick F Lang, Rachel Giles, Eric Jonasch

Faculty, Staff and Student Publications

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of …

Auto-Detection And Segmentation Of Involved Lymph Nodes In Hpv-Associated Oropharyngeal Cancer Using A Convolutional Deep Learning Neural Network, Nicolette Taku, Kareem A Wahid, Lisanne V Van Dijk, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

PURPOSE: Segmentation of involved lymph nodes on head and neck computed tomography (HN-CT) scans is necessary for the radiotherapy planning of early-stage human papilloma virus (HPV) associated oropharynx cancers (OPC). We aimed to train a deep learning convolutional neural network (DL-CNN) to segment involved lymph nodes on HN-CT scans.

METHODS: Ground-truth segmentation of involved nodes was performed on pre-surgical HN-CT scans for 90 patients who underwent levels II-IV neck dissection for node-positive HPV-OPC (training/validation [n = 70] and testing [n = 20]). A 5-fold cross validation approach was used to train 5 DL-CNN sub-models based on a residual U-net architecture. …

Schwann Cells Induce Phenotypic Changes In Oral Cancer Cells, Maria Daniela Santi, Morgan Zhang, Elizabeth Salvo, Kesava Asam, Chi T Viet, Tongxin Xie, Moran Amit, Bradley Aouizerat, Yi Ye

Faculty, Staff and Student Publications

Head and neck cancer (HNC) is the seventh most common cancer worldwide, the majority being oral squamous cell carcinoma. Despite advances in cancer diagnosis and treatment, the survival rate of patients with HNC remains stagnant. The cancer-nerve interaction has been recognized as an important driver of cancer progression. Schwann cells, a type of peripheral glia, have been implicated in promoting cancer cell growth, migration, dispersion, and invasion into the nerve in many cancers. Here, it is demonstrated that the presence of Schwann cells makes oral cancer cells more aggressive by promoting their proliferation, extracellular matrix breakdown, and altering cell metabolism. …

Metagenomes Of Rectal Swabs In Larger, Advanced Stage Cervical Cancers Have Enhanced Mucus Degrading Functionalities And Distinct Taxonomic Structure, Tatiana V Karpinets, Xiaogang Wu, Travis Solley, Molly B El Alam, Travis T Sims, Kyoko Yoshida-Court, Erica Lynn, Mustapha Ahmed-Kaddar, Greyson Biegert, Jingyan Yue, Xingzhi Song, Huandong Sun, Joseph F Petrosino, Melissa P Mezzari, Pablo Okhuysen, Patricia J Eifel, Anuja Jhingran, Lilie L Lin, Kathleen M Schmeler, Lois Ramondetta, Nadim Ajami, Robert R Jenq, Andrew Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC.

METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics.

RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified …

Changes In Apparent Diffusion Coefficient (Adc) In Serial Weekly Mri During Radiotherapy In Patients With Head And Neck Cancer: Results From The Predict-Hn Study, Sweet Ping Ng, Carlos E Cardenas, Houda Bahig, Baher Elgohari, Jihong Wang, Jason M Johnson, Amy C Moreno, Shalin J Shah, Adam S Garden, Jack Phan, G Brandon Gunn, Steven J Frank, Yao Ding, Lumine Na, Ying Yuan, Diana Urbauer, Abdallah S R Mohamed, David I Rosenthal, William H Morrison, Michael P Macmanus, Clifton D Fuller

Faculty, Staff and Student Publications

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy.

Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time.

Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that …

Contributions Of Circulating Micrornas For Early Detection Of Lung Cancer, Jody Vykoukal, Johannes F Fahrmann, Nikul Patel, Masayoshi Shimizu, Edwin J Ostrin, Jennifer B Dennison, Cristina Ivan, Gary E Goodman, Mark D Thornquist, Matt J Barnett, Ziding Feng, George A Calin, Samir M Hanash

Faculty, Staff and Student Publications

There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) …

Molecular Analysis Of Short- Versus Long-Term Survivors Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Emine Bayraktar, Graziela Zibetti Dal Molin, Sherry Y Wu, Lingegowda S Mangala, Hui Yao, Ying Wang, Prahlad T Ram, Sara Corvigno, Hu Chen, Han Liang, Shelley S Tworoger, Douglas A Levine, Susan K Lutgendorf, Jinsong Liu, Kathleen N Moore, Keith A Baggerly, Beth Y Karlan, Anil K Sood

Faculty, Staff and Student Publications

Despite having similar histologic features, patients with high-grade serous ovarian carcinoma (HGSC) often experience highly variable outcomes. The underlying determinants for long-term survival (LTS, ≥10 years) versus short-term survival (STS, < 3 years) are largely unknown. The present study sought to identify molecular predictors of LTS for women with HGSC. A cohort of 24 frozen HGSC samples was collected (12 LTS and 12 STS) and analyzed at DNA, RNA, and protein levels. OVCAR5 and OVCAR8 cell lines were used for in vitro validation studies. For in vivo studies, we injected OVCAR8 cells into the peritoneal cavity of female athymic nude mice. From RNAseq analysis, 11 genes were found to be differentially expressed between the STS and LTS groups (fold change > 2; false discovery rate < 0.01). In the subsequent validation cohort, transmembrane protein 62 (TMEM62) was found to be related to LTS. CIBERSORT analysis showed that T cells (follicular helper) were found at higher levels in tumors from LTS than STS groups. In vitro data using OVCAR5 and OVCAR8 cells showed decreased proliferation with TMEM62 overexpression and positive correlation with a longevity-regulating pathway (KEGG HSA04213) at the RNA level. In vivo analysis using the OVCAR8-TMEM62-TetON model showed decreased tumor burden in mice with high- vs. low-expressing TMEM62 tumors. Our results demonstrate that restoring TMEM62 may be a novel approach for treatment of HGSC. These findings may have implications for biomarker and intervention strategies to help improve patient outcomes

Cancer-Driving Mutations Are Enriched In Genic Regions Intolerant To Germline Variation, Dimitrios Vitsios, Ryan S Dhindsa, Dorota Matelska, Jonathan Mitchell, Xuequing Zou, Joshua Armenia, Fengyuan Hu, Quanli Wang, Ben Sidders, Andrew R Harper, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic subregions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. We hypothesized that cancer-driving mutations might be enriched in genic subregions that are depleted of germline variation relative to somatic variation. We introduce a new metric, OncMTR (oncology missense tolerance ratio), which uses 125,748 exomes in the Genome Aggregation Database (gnomAD) to identify these genic subregions. We demonstrate that OncMTR can significantly predict driver mutations …

Klf5 Governs Sphingolipid Metabolism And Barrier Function Of The Skin, Ying Lyu, Yinglu Guan, Lisa Deliu, Ericka Humphrey, Joanna K Frontera, Youn Joo Yang, Daniel Zamler, Kun Hee Kim, Vakul Mohanty, Kevin Jin, Vakul Mohanty, Virginia Liu, Jinzhuang Dou, Lucas J Veillon, Shwetha V Kumar, Philip L Lorenzi, Yang Chen, Kathleen M Mcandrews, Sergei Grivennikov, Xingzhi Song, Jianhua Zhang, Yuanxin Xi, Jing Wang, Ken Chen, Priyadharsini Nagarajan, Yejing Ge

Faculty, Staff and Student Publications

Stem cells are fundamental units of tissue remodeling whose functions are dictated by lineage-specific transcription factors. Home to epidermal stem cells and their upward-stratifying progenies, skin relies on its secretory functions to form the outermost protective barrier, of which a transcriptional orchestrator has been elusive. KLF5 is a Krüppel-like transcription factor broadly involved in development and regeneration whose lineage specificity, if any, remains unclear. Here we report KLF5 specifically marks the epidermis, and its deletion leads to skin barrier dysfunction in vivo. Lipid envelopes and secretory lamellar bodies are defective in KLF5-deficient skin, accompanied by preferential loss of complex sphingolipids. …