Genetic Phenomena Commons^™

Impact Of Medicaid Expansion Under The Affordable Care Act On Receipt Of Surgery For Breast Cancer, Leisha C Elmore, Meng Li, Heather Lin, Yu Shen, Simona F Shaitelman, Gildy Babiera, Nina Tamirisa, Isabelle Bedrosian

Faculty, Staff and Student Publications

To determine whether Medicaid expansion under the 2010 Affordable Care Act affected rates of breast cancer surgery.

Background: Data regarding the impact of Medicaid expansion on access to surgical treatment of breast cancer are limited.

Methods: Patients in the National Cancer Database diagnosed with non-metastatic breast cancer between January 1, 2010 and December 31, 2017 and residing in a state that expanded Medicaid in January 2014 or in a state that opted out of expansion were included. A quasi-experimental, difference-in-differences (DID) approach was used to assess rate of omission of surgical treatment.

Results: Of 624,237 patients diagnosed with invasive breast …

Addressing Patient Heterogeneity In Disease Predictive Model Development, Xu Gao, Weining Shen, Jing Ning, Ziding Feng, Jianhua Hu

Faculty, Staff and Student Publications

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of subgroups in patient population if subgroups exist. A mixture of generalized linear models is considered to model the relationship between the disease outcome and patient characteristics and clinical factors, including targeted biomarker profiles. We construct a test statistic based on expectation maximization (EM) algorithm and derive its asymptotic distribution under the null hypothesis. An important computational advantage of the test is that the involved parameter estimates under the complex …

Bintrafusp Alfa, An Anti-Pd-L1:Tgf-Β Trap Fusion Protein, In Patients With Ctdna-Positive, Liver-Limited Metastatic Colorectal Cancer, Van K Morris, Michael J Overman, Michael Lam, Christine M Parseghian, Benny Johnson, Arvind Dasari, Kanwal Raghav, Bryan K Kee, Ryan Huey, Robert A Wolff, John Paul Shen, June Li, Isabel Zorrilla, Ching-Wei D Tzeng, Hop S Tran Cao, Yun Shin Chun, Timothy E Newhook, Nicolas Vauthey, Dzifa Duose, Raja Luthra, Cara Haymaker, Scott Kopetz

Faculty, Staff and Student Publications

Background: Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) CRC, increased TGF-β signaling results in exclusion of anti-tumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor ("TGF-β trap") and anti-PD-L1 antibody.

Methods: Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1200 mg of BA intravenously every 14 days …

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. …

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.

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 …