Neoplasms Commons^™

Ewing's Sarcoma Of The Hand: An Unusual Presentation In A Young Hispanic Male, Dylan B Mcbee, Hope A Bentley, Giancarlo Toledanes

Faculty, Staff and Students Publications

Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and …

Multidimensional Biomarker Predicts Disease Control In Response To Immunotherapy In Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Kevin C Flanagan, Jon Earls, Ian Schillebeeckx, Jeffrey Hiken, Rachel L Wellinghoff, Natalie A Lafranzo, Zachary S Bradley, Joey Babbitt, William H Westra, Raymond Hsu, Lincoln Nadauld, Howard Mcleod, Sean D Firth, Brittany Sharp, Josh Fuller, Vera Vavinskaya, Leisa Sutton, Ida Deichaite, Samuel D Bailey, Vlad C Sandulache, Matthew J Rendo, Orlan K Macdonald, Karim Welaya, James L Wade, Andrew W Pippas, Jennifer Slim, Bruce Bank, Steven J Saccaro, Xingwei Sui, Adil Akhtar, Savitha Balaraman, Steven E Kossman, Scott A Sonnier, Todd D Shenkenberg, Warren L Alexander, Katherine A Price, Charles L Bane, Jessica Ley, David N Messina, Jarret I Glasscock, Ezra E W Cohen, Douglas R Adkins, Eric J Duncavage

Faculty, Staff and Students Publications

PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Dna2 Nuclease Inhibition Confers Synthetic Lethality In Cancers With Mutant P53 And Synergizes With Parp Inhibitors, Helena Folly-Kossi, Joshua D Graves, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

UNLABELLED: The tumor suppressor p53 promotes tumor-suppressive activities including cell-cycle inhibition, apoptosis, senescence, autophagy, and DNA repair. However, somatic mutations in the TP53 gene are one of the most common alterations in human cancers. We previously showed that mutant p53 (mutp53) can bind TopBP1, an ATR activator, to attenuate its ATR-activating function. A partially defective ATR function caused by mutp53 makes cancer cells more vulnerable to inhibitors of other TopBP1-independent ATR activators, such as DNA2. DNA2 plays a role in homologous recombination (HR) repair by resecting DNA ends in double-strand breaks and preparing them for invasion of homologous duplex. Here …

High-Fat Diet, But Not Duration Of Lactation, Increases Mammary Gland Lymphatic Vessel Function And Subsequent Growth Of Inflammatory Breast Cancer Cells, Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC …

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T Lei, Meggie N Young, Matthew V Holt, Diana Fandino, Craig T Vollert, Purba Singh, Mohammad A Alzubi, Anna Malovannaya, Lacey E Dobrolecki, Michael T Lewis, Shunqiang Li, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were …

Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang

Faculty, Staff and Student Publications

Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments …

A Novel Prediction Model Of The Risk Of Pancreatic Cancer Among Diabetes Patients Using Multiple Clinical Data And Machine Learning, Shih-Min Chen, Phan Thanh Phuc, Phung-Anh Nguyen, Whitney Burton, Shwu-Jiuan Lin, Weei-Chin Lin, Christine Y Lu, Min-Huei Hsu, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic cancer is associated with poor prognosis. Considering the increased global incidence of diabetes cases and that individuals with diabetes are considered a high-risk subpopulation for pancreatic cancer, it is critical to detect the risk of pancreatic cancer within populations of person living = with diabetes. This study aimed to develop a novel prediction model for pancreatic cancer risk among patients with diabetes, using = a real-world database containing clinical features and employing numerous artificial intelligent approach algorithms.

METHODS: This retrospective observational study analyzed data on patients with Type 2 diabetes from a multisite Taiwanese EMR database between 2009 …

Differential Effects Of Pancreatic Cancer-Derived Extracellular Vesicles Driving A Suppressive Environment, Anurag Purushothaman, Jacqueline Oliva-Ramírez, Warapen Treekitkarnmongkol, Deivendran Sankaran, Mark W Hurd, Nagireddy Putluri, Anirban Maitra, Cara Haymaker, Subrata Sen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) cells display extensive crosstalk with their surrounding environment to regulate tumor growth, immune evasion, and metastasis. Recent advances have attributed many of these interactions to intercellular communication mediated by small extracellular vesicles (sEVs), involving cancer-associated fibroblasts (CAF). To explore the impact of sEVs on monocyte lineage transition as well as the expression of checkpoint receptors and activation markers, peripheral blood monocytes from healthy subjects were exposed to PDAC-derived sEVs. Additionally, to analyze the role of sEV-associated HA in immune regulation and tissue-resident fibroblasts, monocytes and pancreatic stellate cells were cultured in the presence of PDAC sEVs …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

Cardiovascular Disease And Stroke In Immune Ttp-Challenges And Opportunities, Senthil Sukumar, Marshall A Mazepa, Shruti Chaturvedi

Faculty, Staff and Students Publications

Advances in the management of immune thrombotic thrombocytopenic purpura (iTTP) have dramatically improved outcomes of acute TTP episodes, and TTP is now treated as a chronic, relapsing disorder. It is now recognized that iTTP survivors are at high risk for vascular disease, with stroke and myocardial infarction occurring at younger ages than in the general population, and cardiovascular disease is the leading cause of premature death in this population. iTTP appears to have a phenotype of accelerated vascular aging with a particular predilection for cerebral circulation, and stroke is much more common than myocardial infarction. In addition to traditional cardiovascular …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …

Characteristics And Clinical Outcomes Of Patients With Acute Myeloid Leukemia With Inv(3)(Q21q262) Or T(3; 3)(Q21; Q262), Guillaume Richard-Carpentier, Caitlin R Rausch, Koji Sasaki, Danielle Hammond, Kiyomi Morita, Koichi Takahashi, Guilin Tang, Rashmi Kanagal-Shamanna, Kapil Bhalla, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Elizabeth J Shpall, Amin Alousi, Naval G Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission …

Anesthesia Care Provider Sedation Versus Conscious Sedation For Endoscopic Ultrasound-Guided Tissue Acquisition: A Retrospective Cohort Study, Sneha Shaha, Yinglin Gao, Jiahao Peng, Kendrick Che, John J Kim, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition.

METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS).

RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in …

Screening People On Standing Balance With Romberg Testing And Walking Balance With Tandem Walking, Helen S Cohen

Faculty, Staff and Students Publications

The goal of this protocol is to inform readers about the exact procedures to use to perform two screening tests for vestibular disorders: tandem walking (TW) with eyes closed, also known as heel-toe walking, and the Clinical Test of Sensory Integration and Balance (CTSIB), which is also known as the modified Romberg. The study describes the steps for performing each test and each of the three CTSIB subtests so that the reader will be able to replicate the test conditions for use in the clinic, in the clinical laboratory, or in any other situation needing valid and reliable screening for …

Risks Factors And Outcomes For Isolated Catheter-Related Deep Venous Thrombosis In Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation, Jonathan Avery, Danielle Guffey, Shengling Ma, Ryan Basom, Stephanie J Lee, David Garcia, Cristhiam M Rojas Hernandez, Ang Li, Kylee L Martens

Faculty, Staff and Students Publications

INTRODUCTION: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear.

MATERIALS AND METHODS: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was …

Detection Method Has Independent Prognostic Significance In The Plco Lung Screening Trial, James P Long, Yu Shen

Faculty, Staff and Student Publications

Prognostic models in cancer use patient demographic and tumor characteristics to predict survival and dynamic disease prognosis. Past work in breast cancer has shown that cancer detection method, screen-detected or symptom-detected, has prognostic significance. We investigate this phenomenon in the lung component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. Patients were randomized to intervention, receiving four annual chest x-rays (CXRs), or to control, receiving usual care. Patients were followed for a total of approximately 13 years. In PLCO, lung cancer detection method has independent prognostic value exceeding that of variables commonly used in lung cancer prognostic models, …

Proteogenomic Data And Resources For Pan-Cancer Analysis, Yize Li, Yongchao Dou, Felipe Da Veiga Leprevost, Yifat Geffen, Anna P Calinawan, François Aguet, Yo Akiyama, Shankara Anand, Chet Birger, Song Cao, Rekha Chaudhary, Padmini Chilappagari, Marcin Cieslik, Antonio Colaprico, Daniel Cui Zhou, Corbin Day, Marcin J Domagalski, Myvizhi Esai Selvan, David Fenyö, Steven M Foltz, Alicia Francis, Tania Gonzalez-Robles, Zeynep H Gümüş, David Heiman, Michael Holck, Runyu Hong, Yingwei Hu, Eric J Jaehnig, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A Ketchum, Robert J Klein, Jonathan T Lei, Wen-Wei Liang, Yuxing Liao, Caleb M Lindgren, Weiping Ma, Lei Ma, Michael J Maccoss, Fernanda Martins Rodrigues, Wilson Mckerrow, Ngoc Nguyen, Robert Oldroyd, Alexander Pilozzi, Pietro Pugliese, Boris Reva, Paul Rudnick, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Deepak Singhal, Xiaoyu Song, Erik Storrs, Nadezhda V Terekhanova, Ratna R Thangudu, Mathangi Thiagarajan, Liang-Bo Wang, Joshua M Wang, Ying Wang, Bo Wen, Yige Wu, Matthew A Wyczalkowski, Yi Xin, Lijun Yao, Xinpei Yi, Hui Zhang, Qing Zhang, Maya Zuhl, Gad Getz, Li Ding, Alexey I Nesvizhskii, Pei Wang, Ana I Robles, Bing Zhang, Samuel H Payne

Faculty, Staff and Students Publications

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 tumors in 10 cohorts to create a cohesive and powerful dataset for scientific discovery. We outline efforts by the CPTAC pan-cancer working group in data harmonization, data dissemination, and computational resources for aiding biological discoveries. We also discuss challenges for multi-omics data integration and analysis, specifically the unique challenges of working with both nucleotide sequencing and mass spectrometry …

Spatial Transcriptomics Of Intraductal Papillary Mucinous Neoplasms Of The Pancreas Identifies Nkx6-2 As A Driver Of Gastric Differentiation And Indolent Biological Potential, Marta Sans, Yuki Makino, Jimin Min, Kimal I Rajapakshe, Michele Yip-Schneider, C Max Schmidt, Mark W Hurd, Jared K Burks, Javier A Gomez, Fredrik I Thege, Johannes F Fahrmann, Robert A Wolff, Michael P Kim, Paola A Guerrero, Anirban Maitra

Faculty, Staff and Student Publications

Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Definitive Liver Radiotherapy For Intrahepatic Cholangiocarcinoma With Extrahepatic Metastases, Brian De, Rituraj Upadhyay, Kaiping Liao, Tiffany Kumala, Christopher Shi, Grace Dodoo, Joseph Abi Jaoude, Kelsey L Corrigan, Gohar S Manzar, Kathryn E Marqueen, Vincent Bernard, Sunyoung S Lee, Kanwal P S Raghav, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Grace Lee, Jennifer Y Wo, Theodore S Hong, Christopher H Crane, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Milind Javle, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT.

METHODS: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by …

Deployment Of Cisplatin In Veterans With Oropharyngeal Cancer: Toxicity And Impact On Oncologic Outcomes, Ola Soliman, David C Wilde, Jan O Kemnade, Anita L Sabichi, George Chen, Albert Chen, Samantha N Little, Andrew T Huang, David J Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVE: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity.

METHODS: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab.

RESULTS: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along …

Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC.

METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, …

Real-World Perspectives And Practices For Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use In Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer, Hope S Rugo, Christine L Crossno, Yaron B Gesthalter, Kristen Kelley, Heather B Moore, Mothaffar F Rimawi, Kelly E Westbrook, Saundra S Buys

Faculty, Staff and Students Publications

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8%

Venous Thromboembolism Risk In Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Versus Chemotherapy, Ang Li, Sarah B May, Jennifer La, Kylee L Martens, Christopher I Amos, Christopher R Flowers, Nhan V Do, Mary T Brophy, Vipul Chitalia, Katya Ravid, John Michael Gaziano, Nathanael R Fillmore

Faculty, Staff and Students Publications

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer …