Medicine and Health Sciences Commons^™

A Phase 1 Study Of Idh305 In Patients With Idh1 R132-Mutant Acute Myeloid Leukemia Or Myelodysplastic Syndrome, Courtney D Dinardo, Andreas Hochhaus, Mark G Frattini, Karen Yee, Thomas Zander, Alwin Krämer, Xueying Chen, Yan Ji, Nehal S Parikh, Joanne Choi, Andrew H Wei

Faculty, Staff and Student Publications

Purpose: Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). IDH305 is an orally bioavailable, brain-penetrant, mutant-selective allosteric IDH1 inhibitor demonstrating target engagement in preclinical models. This first-in human study was designed to identify the recommended dose for expansion/maximum tolerated dose of IDH305 in patients with IDH1R132-mutant acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Methods: IDH305 was given at doses 75-750 mg twice daily in 41 patients with IDH1R132-mutant AML/MDS. Dose escalation was designed using Bayesian hierarchical model with overdose control principle and relationship with dose-limiting …

Expansion Of The Genotypic And Phenotypic Spectrum Of Ctcf-Related Disorder Guides Clinical Management: 43 New Subjects And A Comprehensive Literature Review, Hannah Gabriela Valverde De Morales, Hsiao-Lin V Wang, Kathryn Garber, Xiaodong Cheng, Victor G Corces, Hong Li

Faculty, Staff and Student Publications

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with …

18f-Fdg Pet/Ct Prediction Of Treatment Outcomes In Human Papillomavirus–Positive, Locally Advanced Oropharyngeal Cancer Patients Receiving Deintensified Therapy: Results From Nrg-Hn002, Rathan M Subramaniam, Lyudmila Demora, Min Yao, Sue S Yom, Maura Gillison, Jimmy J Caudell, John Waldron, Ping Xia, Christine H Chung, Minh Tam Truong, Michelle Echevarria, Jason W Chan, Jessica L Geiger, Loren Mell, Samantha Seaward, Wade L Thorstad, Jonathan Jay Beitler, Khalil Sultanem, Diagjin Blakaj, Quynh-Thu Le

Faculty, Staff and Student Publications

The purpose of this study was to determine the negative predictive value (NPV) of a 12- to 14-wk posttreatment PET/CT for 2-y progression-free survival (PFS) and locoregional control (LRC) in patients with p16-positive locoregionally advanced oropharyngeal cancer (LA-OPC). Study was a secondary endpoint in NRG-HN002, a noncomparative phase II trial in p16-positive LA-OPC, stage T1-T2, N1-N2b or T3, N0-N2b, and ≤10 pack-year smoking. Patients were randomized in a 1:1 ratio to reduced-dose intensity-modulated radiotherapy (IMRT) with or without cisplatin. Methods: PET/CT scans were reviewed centrally. Tumor response evaluations for the primary site, right neck, and left neck were performed using …

Medicaid Expansion And Postoperative Mortality In Women With Gynecologic Cancer: A Difference-In-Difference Analysis, Sarah P Huepenbecker, Shuangshuang Fu, Charlotte C Sun, Hui Zhao, Kristin M Primm, Sharon H Giordano, Larissa A Meyer

Faculty, Staff and Student Publications

BACKGROUND: The association between Medicaid expansion and postoperative mortality after surgery for gynecologic cancer is unknown. Our objective was to compare 30- and 90-day postoperative mortality after gynecologic cancer surgery before and after 2014 in states that did and did not expand Medicaid.

METHODS: We searched the National Cancer Database for women aged 40-64 years old between 2010 and 2016 who underwent surgery for a primary gynecologic malignancy. We used pre/post and quasi-experimental difference-in-difference (DID) multivariable logistic regressions to evaluate mortality pre-2014 (2010-2013) and post-2014 (2014-2016) for states that did and did not expand Medicaid in January 2014. We completed …

Deep Learning-Based Pathology Image Analysis Predicts Cancer Progression Risk In Patients With Oral Leukoplakia, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Roberta Rayra Martins-Chaves, Ricardo Santiago Gomez, Nadarajah Vigneswaran, Arunangshu Sarkar, William N William, Vassiliki Papadimitrakopoulou, Michelle Williams, Diana Bell, Doreen Palsgrove, Justin Bishop, John V Heymach, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Scott M Lippman, Curtis Rg Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models.

METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could …

Use Of Contrast Media During Ct-Guided Thermal Ablation Of Colorectal Liver Metastasis For Procedure Planning Is Associated With Improved Immediate Outcomes, Iwan Paolucci, Yuan-Mao Lin, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.

MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used …

Electrophysiological Normative Responses To Emotional, Neutral, And Cigarette-Related Images, Francesco Versace, Nicola Sambuco, Menton M Deweese, Paul M Cinciripini

Faculty, Staff and Student Publications

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of …

Dosimetric Response Of Gafchromic™ Ebt-Xd Film To Therapeutic Protons, Fada Guan, Xiaochun Wang, Ming Yang, Emily Draeger, Dae Han, Kiminori Iga, Fanqing Guo, Luis Perles, Yuting Li, Narayan Sahoo, Radhe Mohan, Zhe Chen

Faculty, Staff and Student Publications

The EBT-XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared with its predecessor models. This characteristic has made EBT-XD films suitable for high-dose applications, such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra-high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT-XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot-scanning proton beam was used to study LET dependence at three dose-averaged LET values of 1.0 keV/μm, 3.6 keV/μm, and 7.6 …

Author Correction: Neoadjuvant Relatlimab And Nivolumab In Resectable Melanoma, Rodabe N Amaria, Michael Postow, Elizabeth M Burton, Michael T Tetzlaff, Merrick I Ross, Carlos Torres-Cabala, Isabella C Glitza, Fei Duan, Denái R Milton, Klaus Busam, Lauren Simpson, Jennifer L Mcquade, Michael K Wong, Jeffrey E Gershenwald, Jeffrey E Lee, Ryan P Goepfert, Emily Z Keung, Sarah B Fisher, Allison Betof-Warner, Alexander N Shoushtari, Margaret Callahan, Daniel Coit, Edmund K Bartlett, Danielle Bello, Parisa Momtaz, Courtney Nicholas, Aidi Gu, Xuejun Zhang, Brinda Rao Korivi, Madhavi Patnana, Sapna P Patel, Adi Diab, Anthony Lucci, Victor G Prieto, Michael A Davies, James P Allison, Padmanee Sharma, Jennifer A Wargo, Charlotte Ariyan, Hussein A Tawbi

Faculty, Staff and Student Publications

No abstract provided.

Quality Of Life For Men With Metastatic Castrate-Resistant Prostate Cancer Participating In An Aerobic And Resistance Exercise Pilot Intervention, Crystal S. Langlais, Yea-Hung Chen, Erin L. Van Blarigan, June M. Chan, Charles J. Ryan, Li Zhang, Hala T. Borno, Robert U. Newton, Anthony Luke, Alexander S. Bang, Neil Panchal, Imelda Tenggara, Brooke Schultz, Emil Lavaki, Nicole Pinto, Rahul Aggarwal, Terence Friedlander, Vadim S. Koshkin, Andrea L. Harzstark, Eric J. Small, Stacey A. Kenfield

Research outputs 2022 to 2026

Background: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood. Methods: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated …

Association Of Computed Tomography Measures Of Muscle And Adipose Tissue And Progressive Changes Throughout Treatment With Clinical Endpoints In Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors, Azim Khan, Christopher J. Welman, Afaf Abed, Susan O’Hanlon, Andrew Redfern, Sara Azim, Pedro Lopez, Favil Singh, Adnan Khattak

Research outputs 2022 to 2026

To investigate the association between skeletal muscle mass and adiposity measures with disease-free progression (DFS) and overall survival (OS) in patients with advanced lung cancer receiving immunotherapy, we retrospectively analysed 97 patients (age: 67.5 ± 10.2 years) with lung cancer who were treated with immunotherapy between March 2014 and June 2019. From computed tomography scans, we assessed the radiological measures of skeletal muscle mass, and intramuscular, subcutaneous and visceral adipose tissue at the third lumbar vertebra. Patients were divided into two groups based on specific or median values at baseline and changes throughout treatment. A total number of 96 patients …

Systemic Lupus Erythematosus And Mortality In Elderly Patients With Early Breast Cancer, Sebastian Bruera, Xiudong Lei, Xerxes Pundole, Hui Zhao, Sharon H Giordano, Surabhi Vinod, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Objective: Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE.

Methods: We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, …

Crispr/Cas9 Screen Uncovers Functional Translation Of Cryptic Lncrna-Encoded Open Reading Frames In Human Cancer, Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen

Faculty, Staff and Students Publications

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was …

The Tumor-Immune Ecosystem In Shaping Metastasis, Yang Gao, Jeffrey M Rosen, Xiang H-F Zhang

Faculty, Staff and Students Publications

A better understanding of the mechanisms regulating cancer metastasis is critical to develop new therapies and decrease mortality. Emerging evidence suggests that the interactions between tumor cells and the host immune system play important roles in establishing metastasis. Tumor cells are able to recruit immune cells, which in turn promotes tumor cell invasion, intravasation, survival in circulation, extravasation, and colonization in different organs. The tumor-host immunological interactions also generate a premetastatic niche in distant organs which facilitates metastasis. In this review, we summarize the recent findings on how tumor cells and immune cells regulate each other to coevolve and promote …

Trends In Up-To-Date Colorectal Cancer Screening Among Us Adults Aged 50-75 Years And Variations By Race/Ethnicity And Us Census Bureau Divisions, Itunu O Sokale, Omar Rosales, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

INTRODUCTION: Mortality rates from colorectal cancer have declined over the past decades owing to population-based life-saving screening interventions. However, screening inequalities continue among racial and ethnic minorities despite having a higher disease burden. In this study, we assessed the patterns of up-to-date colorectal cancer screening rates among racial/ethnic groups across the U.S. Census Bureau Divisions.

METHODS: This population-based cross-sectional study used weighted data from 4 cycles of the Behavioral Risk Factors Surveillance System (2014, 2016, 2018, and 2020) of adults aged 50‒75 years without a previous diagnosis of colorectal cancer. The primary outcome was guideline-recommended up-to-date colorectal cancer screening. We …

A Scoping Review Of Randomized Clinical Trials For Pain Management In Pediatric Tonsillectomy And Adenotonsillectomy, Michael C Shih, Barry D Long, Phayvanh P Pecha, David R White, Yi-Chun C Liu, Emily Brennan, Mariam I Nguyen, Clarice S Clemmens

Faculty, Staff and Students Publications

OBJECTIVES: To examine the volume, topics, and reporting trends in the published literature of randomized clinical trials for pharmacologic pain management of pediatric tonsillectomy and adenotonsillectomy and to identify areas requiring further research.

DATA SOURCES: PubMed (National Library of Medicine and National Institutes of Health), Scopus (Elsevier), CINAHL (EBSCO), and Cochrane Library (Wiley).

METHODS: A systematic search of four databases was conducted. Only randomized controlled or comparison trials examining pain improvement with a pharmacologic intervention in pediatric tonsillectomy or adenotonsillectomy were included. Data collected included demographics, pain-related outcomes, sedation scores, nausea/vomiting, postoperative bleeding, types of drug comparisons, modes of administration, …

Risk Factors For Hcc In Contemporary Cohorts Of Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Xiangjun Gu, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk.

APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on …

Fine Needle Aspiration Of Pancreatic Lesions Focusing On Secondary Tumors With Emphasis Of Metastatic Breast Cancer: A Clinicopathological Study With Follow-Up, Maria Yanqing Chen, Neda Zarrin-Khameh, Ya Xu

Faculty, Staff and Students Publications

BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed …

Juvenile-Type Granulosa Cell Tumor In Pregnancy Presenting As A Ruptured Abdominal Mass, Odinaka Mogor, Steven Feinstein, Glen Friedman, Jose Salvador Saldivar, Melissa Mendez

HCA Healthcare Journal of Medicine

Introduction

Granulosa cell tumors (GCTs) are part of the sex cord-stromal tumors occurring with a rare incidence rate that only makes up about 2-5% of all ovarian malignancies.

Case Presentation

A 28-year-old woman, gravida 2, para 1, presented with a juvenile-type granulosa cell tumor at 31 weeks gestation, which appeared as a rapidly growing mass with rupture. She underwent an exploratory laparotomy with unilateral salpingo-oophorectomy, and consequently had a successful vaginal delivery. Post-operatively she was treated with paclitaxel and carboplatin chemotherapy regimen with no evidence of recurrence after one year.

Conclusion

Radical surgical management is recommended for these tumors due …

Higher Doses Of Tisagenlecleucel Are Associated With Improved Outcomes: A Report From The Pediatric Real-World Car Consortium., Heather E. Stefanski, Anne Eaton, Christina Baggott, Jenna Rossoff, Michael R. Verneris, Snehit Prabhu, Holly L. Pacenta, Christine L. Phillips, Julie-An Talano, Amy Moskop, Steven P. Margossian, Douglas Myers, Nicole A. Karras, Patrick A. Brown, Muna Qayed, Michelle Hermiston, Prakash Satwani, M Christa Krupski, Amy K. Keating, Rachel Wilcox, Cara A. Rabik, Vanessa A. Fabrizio, Vasant Chinnabhandar, A Yasemin Goksenin, Kevin J. Curran, Crystal L. Mackall, Theodore W. Laetsch, Liora M. Schultz

Manuscripts, Articles, Book Chapters and Other Papers

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if …

Determinants And Mechanisms Of The Low Fusogenicity And High Dependence On Endosomal Entry Of Omicron Subvariants, Panke Qu, John P Evans, Chaitanya Kurhade, Cong Zeng, Yi-Min Zheng, Kai Xu, Pei-Yong Shi, Xuping Xie, Shan-Lu Liu

Faculty, Staff and Student Publications

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced …

Allosteric Autoregulation Of Dna Binding Via A Dna-Mimicking Protein Domain: A Biophysical Study Of Znf410-Dna Interaction Using Small Angle X-Ray Scattering, Gundeep Kaur, Ren Ren, Michal Hammel, John R Horton, Jie Yang, Yu Cao, Chenxi He, Fei Lan, Xianjiang Lan, Gerd A Blobel, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

ZNF410 is a highly-conserved transcription factor, remarkable in that it recognizes a 15-base pair DNA element but has just a single responsive target gene in mammalian erythroid cells. ZNF410 includes a tandem array of five zinc-fingers (ZFs), surrounded by uncharacterized N- and C-terminal regions. Unexpectedly, full-length ZNF410 has reduced DNA binding affinity, compared to that of the isolated DNA binding ZF array, both in vitro and in cells. AlphaFold predicts a partially-folded N-terminal subdomain that includes a 30-residue long helix, preceded by a hairpin loop rich in acidic (aspartate/glutamate) and serine/threonine residues. This hairpin loop is predicted by AlphaFold to …

Jaml Immunotherapy Targets Recently Activated Tumor-Infiltrating Cd8+ T Cells, Simon Eschweiler, Alice Wang, Ciro Ramírez-Suástegui, Adrian Von Witzleben, Yingcong Li, Serena J Chee, Hayley Simon, Monalisa Mondal, Matthew Ellis, Gareth J Thomas, Vivek Chandra, Christian H Ottensmeier, Pandurangan Vijayanand

Faculty, Staff and Student Publications

Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly …

Prognostic Significance Of Acellular Mucin In Patients Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy (Crs/Hipec) For Appendiceal Neoplasms, Derek J Erstad, Kristen A Robinson, Karen Beaty, Safia Rafeeq, Yi-Ju Chiang, Kanwal Raghav, John P Shen, Michael J Overman, Wai Chin Foo, Melissa W Taggart, Paul F Mansfield, Richard E Royal, Keith F Fournier, Christopher P Scally

Faculty, Staff and Student Publications

Introduction: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients.

Methods: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed.

Results: Median age was 51 years, 70% were female, …

Cedar: Incorporating Cell Type Hierarchy Improves Cell Type-Specific Differential Analyses In Bulk Omics Data, Luxiao Chen, Ziyi Li, Hao Wu

Faculty, Staff and Student Publications

Bulk high-throughput omics data contain signals from a mixture of cell types. Recent developments of deconvolution methods facilitate cell type-specific inferences from bulk data. Our real data exploration suggests that differential expression or methylation status is often correlated among cell types. Based on this observation, we develop a novel statistical method named CeDAR to incorporate the cell type hierarchy in cell type-specific differential analyses of bulk data. Extensive simulation and real data analyses demonstrate that this approach significantly improves the accuracy and power in detecting cell type-specific differential signals compared with existing methods, especially in low-abundance cell types.

Recovering False Negatives In Crispr Fitness Screens With Jloe, Merve Dede, Traver Hart

Faculty, Staff and Student Publications

It is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared …

Analysis Of Acquired Resistance Mechanisms To Osimertinib In Patients With Egfr-Mutated Advanced Non-Small Cell Lung Cancer From The Aura3 Trial, Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A Shepherd, Krishna C Bulusu, Gianluca Laus, Barbara Collins, J Carl Barrett, Ryan J Hartmaier, Vassiliki Papadimitrakopoulou

Faculty, Staff and Student Publications

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation …

Kras-Mutant Lung Cancer: Targeting Molecular And Immunologic Pathways, Therapeutic Advantages And Restrictions, Nastaran Karimi, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

RAS mutations are among the most common oncogenic mutations in human cancers. Among RAS mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and …

Impact Of Timing To Initiate Adjuvant Therapy On Survival Of Elderly Glioblastoma Patients Using The Seer-Medicare And National Cancer Databases, Ping Zhu, Xianglin L Du, Lu-Yu Hwang, David Lairson, Ruosha Li, Yoshua Esquenazi, Jay-Jiguang Zhu

Faculty, Staff and Student Publications

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 …

Interprofessional Collaboration Optimizes Oncology Navigation Efficiency And Value​, Lauri Ledbeter, Whitney Daws, Rebekah Hart, Lindsay Shimizu

Providence Nursing Research Conference 2023 – Present

Background: Oncology navigation programs have evolved to include services for addressing cancer care barriers, focusing on care coordination, patient experience, and care value, and may include nurses, social workers, and non-licensed trained workers as care navigators. The 2023 Enhancing Oncology Payment Model (EOPM) requires navigation services and emphasizes improving care value and outcomes. Effective healthcare navigation and collaboration can improve value by reducing care duplication, missed appointments, and emergency admissions; identifying and addressing health-related social needs; addressing health inequities; and improving time-to-treatment initiation and patient retention. The Institute of Medicine also advocates for healthcare professionals to work interprofessionally, implement quality …