Medicine and Health Sciences Commons^™

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. …

Cancer-Specific Survival After Diagnosis In Men Versus Women: A Pan-Cancer Analysis., Yan He, Yonglin Su, Junsong Zeng, Weelic Chong, Xiaolin Hu, Yu Zhang, Xingchen Peng

Department of Medical Oncology Faculty Papers

Comprehensive understanding of cancer-specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer-specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer-specific survival. Among the included cancer types, female patients showed survival benefit in lung, …

Association Between Acute Kidney Injury And Long-Term Mortality In Patients With Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study, Yangchun Xiao, Jun Wan, Yu Zhang, Xing Wang, Hanwen Zhou, Han Lai, Weelic Chong, Yang Hai, L Dade Lunsford, Chao You, Shui Yu, Fang Fang

Department of Medical Oncology Faculty Papers

Background: Though acute kidney injury (AKI) in the context of aneurysmal subarachnoid hemorrhage (aSAH) worsens short-term outcomes, its impact on long-term survival is unknown.

Aim: We aimed to evaluate the association between long-term mortality and AKI during hospitalization for aSAH.

Methods: This was a retrospective study of patients who survived >12 months after aSAH. All patients were evaluated at West China Hospital, Sichuan University, between December 2013 and June 2019. The minimum follow-up time was over 1 year. the maximum follow-up time was about 7.3 years. AKI was defined by the KDIGO (The Kidney Disease Improving Global Outcomes) guidelines, which …

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 …

Rates Of Laboratory Adverse Events By Course In Paediatric Leukaemia Ascertained With Automated Electronic Health Record Extraction: A Retrospective Cohort Study From The Children’S Oncology Group, Tamara P Miller, Kelly D Getz, Yimei Li, Biniyam G Demissei, Peter C Adamson, Todd A Alonzo, Evanette Burrows, Lusha Cao, Sharon M Castellino, Marla H Daves, Brian T Fisher, Robert Gerbing, Robert W Grundmeier, Edward M Krause, Judy Lee, Philip J Lupo, Karen R Rabin, Mark Ramos, Michael E Scheurer, Jennifer J Wilkes, Lena E Winestone, Douglas S Hawkins, M Monica Gramatges, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.

Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia …

Risk Score Using Demographic And Clinical Risk Factors Predicts Gastric Intestinal Metaplasia Risk In A Us Population, Mimi C Tan, Quynh Ho, Theresa H Nguyen, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S.

METHODS: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. …

Outcomes For Endoscopic Submucosal Dissection Of Pathologically Staged T1b Esophageal Cancer: A Multicenter Study, Abel Joseph, Peter V Draganov, Fauze Maluf-Filho, Hiroyuki Aihara, Norio Fukami, Neil R Sharma, Amitabh Chak, Dennis Yang, Salmaan Jawaid, John Dumot, Omar Alaber, Tiffany Chua, Rituraj Singh, Lady Katherine Mejia-Perez, Ruishen Lyu, Xuefeng Zhang, Suneel Kamath, Sunguk Jang, Sudish Murthy, John Vargo, Amit Bhatt

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC.

METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates.

RESULTS: Sixty-six patients with pathologically staged T1b EC after …

Effectiveness And Safety Of Immunosuppressants And Biological Therapy For Chronic Spontaneous Urticaria: A Network Meta-Analysis, Wen-Kuang Lin, Shwu-Jiuan Lin, Woan-Ruoh Lee, Chia-Chieh Lin, Weei-Chin Lin, Hua-Ching Chang, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect …

Human Leucocyte Antigen Genotype Association With The Development Of Immune-Related Adverse Events In Patients With Non-Small Cell Lung Cancer Treated With Single Agent Immunotherapy, Afaf Abed, Ngie Law, Leslie Calapre, Johnny Lo, Vikas Bhat, Samantha Bowyer, Michael Millward, Elin S. Gray

Research outputs 2022 to 2026

Introduction: Biomarkers that predict the risk of immune-mediated adverse events (irAEs) among patients with non-small cell lung cancer (NSCLC) may reduce morbidity and mortality associated with these treatments. Methods: We carried out high resolution human leucocyte antigen (HLA)-I typing on 179 patients with NSCLC treated with anti-program death (PD)-1/program death ligand (PDL)-1. Toxicity data were collected and graded as per common terminology criteria for adverse event (CTCAE) v5.0. We used 14.8-week for landmark analysis to address lead-time bias to investigate the correlation between HLA-I/II zygosity, supertypes and alleles with irAE. Furthermore, we assessed the association for irAE with clinical benefit …

Editorial: Promising Strategies For Vaccine Messages: The Message And The Source, Bridget J. Kelly, Amy E. Leader, Nora B. Henrikson

Department of Medical Oncology Faculty Papers

No abstract provided.

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 …

Prevalence, Distribution, And Histopathological Features Of Malignant Tumors Reported At Tertiary Level In Afghanistan: A 3-Year Study, Haider Ali Malakzai, Ahmed Maseh Haidary, Saleema A. Gulzar, Mujtaba Haidari, Abdul Sami Ibrahimkhil, Ramin Saadaat, Ahmadullah Hakimi, Sayed Murtaza Sadat Hofiani, Soma Rahmani, Jamshid Abdul Ghafar

School of Nursing & Midwifery

Purpose: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and …

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

A Scoping Review Protocol To Elucidate Outcomes Following Abiraterone Versus Enzalutamide For Prostate Cancer, Yash B Shah, Amy L Shaver, William Kevin Kelly, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

INTRODUCTION: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, …

Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis In 3d Triculture Model Of Reactive Stroma, Lindsey K Sablatura, Tristen V Tellman, Aemin Kim, Mary C Farach-Carson

Faculty, Staff and Student Publications

The bone marrow tumor microenvironment (BMTE) is a complex network of cells, extracellular matrix, and sequestered signaling factors that initially act as a hostile environment for disseminating tumor cells (DTCs) from the cancerous prostate. Three-dimensional (3D) culture systems offer an opportunity to better model these complex interactions in reactive stroma, providing contextual behaviors for cancer cells, stromal cells, and endothelial cells. Using a new system designed for the triculture of osteoblastic prostate cancer (PCa) cells, stromal cells, and microvascular endothelial cells, we uncovered a context-specific pro-apoptotic effect of endothelial cells of the bone marrow different from those derived from the …

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 …