Neoplasms Commons^™

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Onecut2 Acts As A Lineage Plasticity Driver In Adenocarcinoma As Well As Neuroendocrine Variants Of Prostate Cancer, Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar, Stephen J Freedland, Edwin M Posadas, Leigh Ellis, Dolores Di Vizio, Colm Morrissey, Peter S Nelson, Lauren Brady, Ramachandran Murali, Moray J Campbell, Wei Yang, Beatrice S Knudsen, Elahe A Mostaghel, Huihui Ye, Isla P Garraway, Sungyong You, Michael R Freeman

Faculty, Staff and Students Publications

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic …

Long-Term Survival Follow-Up For Tebentafusp In Previously Treated Metastatic Uveal Melanoma, Joseph Sacco, Richard Carvajal, Marcus Butler, Alexander N Shoushtari, Jessica Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep Piulats, Matthew Rioth, Douglas B Johnson, Jason Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Chris Holland, Takami Sato

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. …

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

Practical Guidance On Establishing A Molecular Testing Pathway For Alterations In Homologous Recombination Repair Genes In Clinical Practice For Patients With Metastatic Prostate Cancer, Martin Schostak, Angela Bradbury, Alberto Briganti, David Gonzalez, Leonard Gomella, Joaquin Mateo, Frédérique Penault-Llorca, Albrecht Stenzinger, Alexander Wyatt, Anders Bjartell

Department of Urology Faculty Papers

CONTEXT: Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach.

OBJECTIVE: To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate …

Escalated-Dose Radiotherapy For Unresected Locally Advanced Pancreatic Cancer: Patterns Of Care And Survival In The United States, Christopher Shi, Brian De, Hop S Tran Cao, Suyu Liu, Marcus A Florez, Ramez Kouzy, Adam J Grippin, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Michael P Kim, Sunyoung Lee, Jason Willis, Sonal S Noticewala, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes.

METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 …

Risk Factors For Early Mortality From Lung Cancer: Evolution Over The Last 20 Years In The French Nationwide Kbp Cohorts, T C T Hoang, D Debieuvre, A-S Bravard, S Martinez, G Le Garff, S Jeandeau, L Petit, D Marquette, K Amrane, P Demontrond, M Tiercin, B Jarjour, A Turlotte, P Masson, M Jaafar, P-A Hauss, H Morel

Faculty, Staff and Students Publications

BACKGROUND: The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years.

MATERIALS AND METHODS: The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. …

Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller

Kimmel Cancer Center Faculty Papers

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.

METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local …

T-Cell Redirecting Bispecific Antibodies: A Review Of A Novel Class Of Immuno-Oncology For Advanced Prostate Cancer, Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick Mille, William Tester, William Kelly, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor …

Glioblastoma Disrupts Cortical Network Activity At Multiple Spatial And Temporal Scales, Jochen Meyer, Kwanha Yu, Estefania Luna-Figueroa, Benjamin Deneen, Jeffrey Noebels

Faculty, Staff and Students Publications

The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and …

A Multi-Institutional Meningioma Mri Dataset For Automated Multi-Sequence Image Segmentation, Dominic Labella, Omaditya Khanna, Shan Mcburney-Lin, Ryan Mclean, Pierre Nedelec, Arif Rashid, Nourel Hoda Tahon, Talissa Altes, Ujjwal Baid, Radhika Bhalerao, Yaseen Dhemesh, Scott Floyd, Devon Godfrey, Fathi Hilal, Anastasia Janas, Anahita Kazerooni, Collin Kent, John Kirkpatrick, Florian Kofler, Kevin Leu, Nazanin Maleki, Bjoern Menze, Maxence Pajot, Zachary Reitman, Jeffrey Rudie, Rachit Saluja, Yury Velichko, Chunhao Wang, Pranav Warman, Nico Sollmann, David Diffley, Khanak Nandolia, Daniel Warren, Ali Hussain, John Pascal Fehringer, Yulia Bronstein, Lisa Deptula, Evan Stein, Mahsa Taherzadeh, Eduardo Portela De Oliveira, Aoife Haughey, Marinos Kontzialis, Luca Saba, Benjamin Turner, Melanie Brüßeler, Shehbaz Ansari, Athanasios Gkampenis, David Maximilian Weiss, Aya Mansour, Islam Shawali, Nikolay Yordanov, Joel Stein, Roula Hourani, Mohammed Yahya Moshebah, Ahmed Magdy Abouelatta, Tanvir Rizvi, Klara Willms, Dann Martin, Abdullah Okar, Gennaro D'Anna, Ahmed Taha, Yasaman Sharifi, Shahriar Faghani, Dominic Kite, Marco Pinho, Muhammad Ammar Haider, Michelle Alonso-Basanta, Javier Villanueva-Meyer, Andreas Rauschecker, Ayman Nada, Mariam Aboian, Adam Flanders, Spyridon Bakas, Evan Calabrese

Department of Radiology Faculty Papers

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by …

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer

Kimmel Cancer Center Faculty Papers

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of …

First-In-Human Phase I Study Of Tinengotinib (Tt-00420), A Multiple Kinase Inhibitor, As A Single Agent In Patients With Advanced Solid Tumors, Sarina A Piha-Paul, Binghe Xu, Ecaterina E Dumbrava, Siqing Fu, Daniel D Karp, Funda Meric-Bernstam, David S Hong, Jordi A Rodon, Apostolia M Tsimberidou, Kanwal Raghav, Jaffer A Ajani, Anthony P Conley, Frank Mott, Ying Fan, Jean Fan, Peng Peng, Hui Wang, Shumao Ni, Caixia Sun, Xiaoyan Qiang, Wendy J Levin, Brenda Ngo, Qinhua Cindy Ru, Frank Wu, Milind M Javle

Faculty, Staff and Student Publications

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors.

PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy.

RESULTS: Forty-eight patients were enrolled (dose escalation, …

Prediction Of Cancer Incidence And Mortality In Korea, 2024, Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo

Faculty, Staff and Student Publications

PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden.

MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Stat5 Induces Androgen Receptor (Ar) Gene Transcription In Prostate Cancer And Offers A Druggable Pathway To Target Ar Signaling, Cristina Maranto, Lavannya Sabharwal, Vindhya Udhane, Samuel P. Pitzen, Braedan Mccluskey, Songyan Qi, Christine O'Connor, Savita Devi, Scott Johnson, Kenneth Jacobsohn, Anjishnu Banerjee, Kenneth A. Iczkowski, Liang Wang, Scott M. Dehm, Marja T. Nevalainen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, …

Simultaneous Detection Of Helicobacter Pylori Infection Comparing Between White Light And Image-Enhanced Endoscopy, Boonyaorn Chatrangsun, Natsuda Aumpan, Bubpha Pornthisarn, Soonthorn Chonprasertsuk, Sith Siramolpiwat, Patommatat Bhanthumkomol, Pongjarat Nunanan, Navapan Issariyakulkarn, Varocha Mahachai, Yoshio Yamaoka, Ratha-Korn Vilaichone

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection.

METHODS: This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand …

Canadian French Translation And Validation Of The Neck Dissection Impairment Index: A Quality Of Life Measure For The Surgical Oncology Population, Michel Khoury, William Guertin, Cameo Hao, Mikhail Saltychev, Tareck Ayad, Eric Bissada, Apostolos Christopoulos, Sami Moubayed, Marie-Jo Olivier, Douglas Chepeha, Stephen Y Lai, Anastasios Maniakas

Faculty, Staff and Student Publications

BACKGROUND: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French.

METHODS: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session …

A Multi-Institutional Natural Language Processing Pipeline To Extract Performance Status From Electronic Health Records, Arash Maghsoudi, Yvonne H Sada, Sara Nowakowski, Danielle Guffey, Huili Zhu, Sudha R Yarlagadda, Ang Li, Javad Razjouyan

Faculty, Staff and Students Publications

PURPOSE: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes.

PATIENTS AND METHODS: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train …

Risk Stratification Model For Hepatocellular Cancer In Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Jennifer R Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.

METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating …

Neurologic Outcomes For Adult Spinal Cord Ependymomas Stratified By Tumor Location: A Retrospective Cohort Study And 2-Year Outlook, Keanu Chee, Grégoire P Chatain, Michael W Kortz, Stephanie Serva, Keshari Shrestha, Timothy H Ung, Jens-Peter Witt, Michael Finn

Department of Neurosurgery Faculty Papers

Determine whether craniocaudal spinal cord tumor location affects long-term neurologic outcomes in adults diagnosed with spinal ependymomas (SE). A retrospective cohort analysis of patients aged ≥ 18 years who underwent surgical resection for SE over a ten-year period was conducted. Tumor location was classified as cervical, thoracic, or lumbar/conus. Primary endpoints were post-operative McCormick Neurologic Scale (MNS) scores at < 3 days, 6 weeks, 1 year, and 2 years. One-way ANOVA was performed to detect significant differences in MNS scores between tumor locations. Twenty-eight patients were identified. The average age was 44.2 ± 15.4 years. Sixteen were male, and 13 were female. There were 10 cervical-predominant SEs, 13 thoracic-predominant SEs, and 5 lumbar/conus-predominant SEs. No significant differences were observed in pre-operative MNS scores between tumor locations (p = 0.73). One-way ANOVA testing demonstrated statistically significant differences in post-operative MNS scores between tumor locations at < 3 days (p = 0.03), 6 weeks (p = 0.009), and 1 year (p = 0.003); however, no significant difference was observed between post-operative MNS scores at 2 years (p = 0.13). The mean MNS score for patients with thoracic SEs were higher at all follow-up time points. Tumors arising in the thoracic SE are associated with worse post-operative neurologic outcomes in comparison to SEs arising in other spinal regions. This is likely multifactorial in etiology, owing to both anatomical differences including spinal cord volume as well as variations in tumor characteristics. No significant differences in 2-year MNS scores were observed, suggesting that patients ultimately recover from neurological insult sustained at the time of surgery.

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 …

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 …

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, …

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 …

Epidemiology Of Cancer-Associated Venous Thromboembolism In Patients With Solid And Hematologic Neoplasms In The Veterans Affairs Health Care System, Kylee L Martens, Ang Li, Jennifer La, Sarah B May, Kaitlin N Swinnerton, Hannah Tosi, Danne C Elbers, Nhan V Do, Mary T Brophy, J Michael Gaziano, Saran Lotfollahzadeh, Vipul Chitalia, Katya Ravid, Nathanael R Fillmore

Faculty, Staff and Students Publications

IMPORTANCE: Identifying changes in epidemiologic patterns of the incidence and risk of cancer-associated thrombosis (CAT), particularly with evolving cancer-directed therapy, is essential for risk stratification.

OBJECTIVE: To assess the incidence of CAT over time and to determine pertinent patient-specific, cancer-specific, and treatment-specific factors associated with its risk.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, retrospective cohort study was conducted from 2006 to 2021. Duration of follow-up was from the date of diagnosis until first venous thromboembolism (VTE) event, death, loss of follow-up (defined as a 90-day gap without clinical encounters), or administrative censoring on April 1, 2022. The study took place …

Pyridoxamine Treatment Ameliorates Large Artery Stiffening And Cerebral Artery Endothelial Dysfunction In Old Mice, Emily H Reeve, Elise K Kronquist, Julia R Wolf, Byron Lee, Aleena Khurana, Hanson Pham, Abigail E Cullen, Jessica A Peterson, Antonio Meza, R Colton Bramwell, Laura Villasana, Daniel R Machin, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old …