Neoplasms Commons^™

Targeted Variant Assessments Of Human Endogenous Retroviral Regions In Whole Genome Sequencing Data Reveal Retroviral Variants Associated With Papillary Thyroid Cancer, Erik Stricker, Erin C Peckham-Gregory, Stephen Y Lai, Vlad C Sandulache, Michael E Scheurer

Faculty, Staff and Students Publications

Papillary thyroid cancer (PTC) is one of the fastest-growing cancers worldwide, lacking established causal factors or validated early diagnostics. Human endogenous retroviruses (HERVs), comprising 8% of human genomes, have potential as PTC biomarkers due to their comparably high baseline expression in healthy thyroid tissues, indicating homeostatic roles. However, HERV regions are often overlooked in genome-wide association studies because of their highly repetitive nature, low sequence coverage, and decreased sequencing quality. Using targeted whole-genome sequence analysis in conjunction with high sequencing depth to overcome methodological limitations, we identified associations of specific HERV variants with PTC. Analyzing WGS data from 138 patients …

What Do Cancer Genetic Providers Want Us To Know About Variant Reclassification And Recontact That We Are Not Asking? A Thematic Analysis Of Open-Ended Survey Responses, Kerri Brown, Marisel Ponton, Elenita Davidson, Banu Arun, Robert J Volk, Sanjay Shete, Susan K Peterson, Sukh Makhnoon

Faculty, Staff and Student Publications

BACKGROUND: Accurate variant classification and relaying reclassified results to patients is critical for hereditary cancer care delivery. Over a 5- to 10-year period, 6%-15% of variants undergo reclassification. As the frequency of reclassifications increases, the issue of whether, how, when, and which providers should recontact patients becomes important but remains contentious.

METHODS: The authors used inductive thematic analysis to analyze open-ended comments offered by oncologists and genetic counselors (GCs) from a large national survey.

RESULTS: Of the 634 oncologists and cancer GCs, 126 (20%) offered substantive free-text comments. Four thematic areas emerged: 1) ambiguity over professional responsibility to recontact, 2) …

Survival In Patients With Rheumatoid Arthritis And Early Breast Cancer Treated With Tumor Necrosis Factor Inhibitors, Juan I Ruiz, Xiudong Lei, Wu Chi-Fang, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Background: There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis.

Methods: We identified patients in two datasets: (1) Optum's de-identified Clinformatics® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs …

Impact Of Artificial Intelligence-Based Autosegmentation Of Organs At Risk In Low- And Middle-Income Countries, Solomon Kibudde, Awusi Kavuma, Yao Hao, Tianyu Zhao, Hiram Gay, Jacaranda Van Rheenen, Pavan Mukesh Jhaveri, Minjmaa Minjgee, Enkhsetseg Vanchinbazar, Urdenekhuu Nansalmaa, Baozhou Sun

Faculty, Staff and Students Publications

PURPOSE: Radiation therapy (RT) processes require significant human resources and expertise, creating a barrier to rapid RT deployment in low- and middle-income countries (LMICs). Accurate segmentation of tumor targets and organs at risk (OARs) is crucial for optimal RT. This study assessed the impact of artificial intelligence (AI)-based autosegmentation of OARs in 2 LMICs.

METHODS AND MATERIALS: Ten patients, comprising 5 head and neck (HN) cancer patients and 5 prostate cancer patients, were randomly selected. Planning computed tomography images were subjected to autosegmentation using an Food and Drug Administration-approved AI software tool and manual segmentation by experienced radiation oncologists from …

Paraneoplastic Acral Vascular Syndrome In A Patient With Advanced Oropharyngeal Squamous Cell Carcinoma; Case Report And Literature Review, Ancuța Năstac, Lucian Negreanu, Alexandru Constantinescu, Octavian Andronic, Andreea Dobromirescu

Journal of Mind and Medical Sciences

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from …

Micrornas Are Enriched At Covid-19 Genomic Risk Regions, And Their Blood Levels Correlate With The Covid-19 Prognosis Of Cancer Patients Infected By Sars-Cov-2, Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A Calin

Faculty, Staff and Student Publications

Background: Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.

Patients and methods: Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in …

Molecular And Clinical Features Of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series, Ashwathy Balachandran Pillai, Mahmoud Yousef, Abdelrahman Yousef, Kristin D Alfaro-Munoz, Brandon G Smaglo, Jason Willis, Robert A Wolff, Shubham Pant, Mark W Hurd, Anirban Maitra, Huamin Wang, Matthew Harold G Katz, Laura R Prakash, Ching-Wei D Tzeng, Rebecca Snyder, Luca F Castelnovo, Anthony Chen, Andrey Kravets, Kseniia Kudriavtseva, Artem Tarasov, Kirill Kryukov, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023-2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing …

A Rare Case Of Metachronous Gastric Lymphoma And Gastric Adenocarcinoma, Rofinna Johnkennedy Md, Mph, Cheng-Hung Tai, Alexa Plato Md, Department Of Medicine,, Caroline Loeser

Posters

Reports of metachronous primary gastric lymphoma and gastric adenocarcinoma exist in the literature, but it remains a rare entity. We present a rare case of metachronous gastric adenocarcinoma in a patient diagnosed initially with primary gastric lymphoma.

Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini

Faculty, Staff and Students Publications

BACKGROUND:NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.

METHODS: Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two

RESULTS AND DISCUSSION: Incubation of degron cells with the small compound dTAG-13 …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

A Systematic Review On The Techniques, Long-Term Outcomes, And Complications Of Partial Breast Irradiation After Breast-Conserving Surgery For Early-Stage Breast Cancer, Jing Ning, Guanghui Cheng, Ning Wu

Faculty, Staff and Student Publications

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk …

The P-Myh9/Usp22/Hif-1Α Axis Promotes Lenvatinib Resistance And Cancer Stemness In Hepatocellular Carcinoma, Qiaonan Shan, Lu Yin, Qifan Zhan, Jiongjie Yu, Sheng Pan, Jianyong Zhuo, Wei Zhou, Jiaqi Bao, Lincheng Zhang, Jiachen Hong, Jianan Xiang, Qingyang Que, Kangchen Chen, Shengjun Xu, Jingrui Wang, Yangbo Zhu, Bin He, Jingbang Wu, Haiyang Xie, Shusen Zheng, Tingting Feng, Sunbin Ling, Xiao Xu

Faculty, Staff and Student Publications

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples …

Frequent Chd1 Deletions In Prostate Cancers Of African American Men Is Associated With Rapid Disease Progression, Miklos Diossy, Viktoria Tisza, Hua Li, Pranshu Sahgal, Jia Zhou, Zsofia Sztupinszki, Denise Young, Darryl Nousome, Claire Kuo, Jiji Jiang, Yongmei Chen, Reinhard Ebner, Isabell A Sesterhenn, Joel T Moncur, Gregory T Chesnut, Gyorgy Petrovics, Gregory T Klus, Gabor Valcz, Pier Vitale Nuzzo, Dezso Ribli, Judit Börcsök, Aurel Prosz, Marcin Krzystanek, Thomas Ried, David Szuts, Kinza Rizwan, Salma Kaochar, Shailja Pathania, Alan D D'Andrea, Istvan Csabai, Shiv Srivastava, Matthew L Freedman, Albert Dobi, Sandor Spisak, Zoltan Szallasi

Faculty, Staff and Students Publications

We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR …

Adaptation Of The Socioecological Model To Address Disparities In Engagement Of Black Men In Prostate Cancer Genetic Testing, Amy Leader, Timothy Rebbeck, William Oh, Alpa Patel, Eric Winer, Leeann Bailey, Leonard Gomella, Crystal Lumpkins, Isla Garraway, Lisa Aiello, Monica Baskin, Heather H Cheng, Kathleen Cooney, Amanda Ganzak, Daniel George, Susan Halabi, Feighanne Hathaway, Claire Healy, Joseph W Kim, Michael Leapman, Stacy Loeb, Kara Maxwell, Christopher Mcnair, Todd Morgan, Breanne Prindeville, Howard R Soule, Whitney Steward, Sakinah Suttiratana, Mary-Ellen Taplin, Kosj Yamoah, Thierry Fortune, Kris Bennett, Joshua Blanding-Godbolt, Laura Gross, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT.

METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa …

A Smart Water Bottle And Companion App (Hidratespark 3) To Improve Bladder-Filling Compliance In Patients With Prostate Cancer Receiving Radiotherapy: Nonrandomized Trial Of Feasibility And Acceptability, William Jin, Christopher Montoya, Benjamin James Rich, Crystal Seldon Taswell, Miguel Noy, Deukwoo Kwon, Benjamin Spieler, Brandon Mahal, Matthew Abramowitz, Raphael Yechieli, Alan Pollack, Alan Dal Pra

Faculty, Staff and Student Publications

Background: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE).

Objective: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE.

Methods: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both …

Mitochondrial Reprogramming By Activating Oxphos Via Glutamine Metabolism In African American Patients With Bladder Cancer, Karthik Reddy Kami Reddy, Danthasinghe Waduge Badrajee Piyarathna, Jun Hyoung Park, Vasanta Putluri, Chandra Sekhar Amara, Abu Hena Mostafa Kamal, Jun Xu, Daniel Kraushaar, Shixia Huang, Sung Yun Jung, Livia S Eberlin, Jabril R Johnson, Rick A Kittles, Leomar Y Ballester, Krishna Parsawar, M Minhaj Siddiqui, Jianjun Gao, Adriana Langer Gramer, Roni J Bollag, Martha K Terris, Yair Lotan, Chad J Creighton, Seth P Lerner, Arun Sreekumar, Benny Abraham Kaipparettu, Nagireddy Putluri

Faculty, Staff and Students Publications

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Neoadjuvant Parpi Or Chemotherapy In Ovarian Cancer Informs Targeting Effector Treg Cells For Homologous-Recombination-Deficient Tumors, Yikai Luo, Yu Xia, Dan Liu, Xiong Li, Huayi Li, Jiahao Liu, Dongchen Zhou, Yu Dong, Xin Li, Yiyu Qian, Cheng Xu, Kangjia Tao, Guannan Li, Wen Pan, Qing Zhong, Xingzhe Liu, Sen Xu, Zhi Wang, Ronghua Liu, Wei Zhang, Wanying Shan, Tian Fang, Siyuan Wang, Zikun Peng, Ping Jin, Ning Jin, Shennan Shi, Yuxin Chen, Mengjie Wang, Xiaofei Jiao, Mengshi Luo, Wenjian Gong, Ya Wang, Yue Yao, Yi Zhao, Xinlin Huang, Xuwo Ji, Zhaoren He, Guangnian Zhao, Rong Liu, Mingfu Wu, Gang Chen, Li Hong, Cocpo Consortium, Ding Ma, Yong Fang, Han Liang, Qinglei Gao

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD …

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

Landmark-Based Auto-Contouring Of Clinical Target Volumes For Radiotherapy Of Nasopharyngeal Cancer, Carlos Sjogreen, Tucker J Netherton, Anna Lee, Moaaz Soliman, Skylar S Gay, Callistus Nguyen, Raymond Mumme, Ivan Vazquez, Dong Joo Rhee, Carlos E Cardenas, Mary K Martel, Beth M Beadle, Laurence Edward Court

Faculty, Staff and Student Publications

Background: The delineation of clinical target volumes (CTVs) for radiotherapy for nasopharyngeal cancer is complex and varies based on the location and extent of disease.

Purpose: The current study aimed to develop an auto-contouring solution following one protocol guidelines (NRG-HN001) that can be adjusted to meet other guidelines, such as RTOG-0225 and the 2018 International guidelines.

Methods: The study used 2-channel 3-dimensional U-Net and nnU-Net framework to auto-contour 27 normal structures in the head and neck (H&N) region that are used to define CTVs in the protocol. To define the CTV-Expansion (CTV1 and CTV2) and CTV-Overall (the outer envelope of …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Factorial Trial To Optimize An Internet-Delivered Intervention For Sexual Health After Breast Cancer: Protocol For The Wf-2202 Sexual Health And Intimacy Enhancement (Shine) Trial, Kelly M. Shaffer, Jennifer Barsky Reese, Emily V. Dressler, Jillian V. Glazer, Wendy Cohn, Shayna L. Showalter, Anita H. Clayton, Suzanne C. Danhauer, Michelle Loch, Mai Kadi, Caleigh Smith, Kathryn E. Weaver, Glenn J. Lesser, Lee M. Ritterband

School of Medicine Faculty Publications

Background: Although most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake. Objective: Guided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention …

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

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 …

Application Of Geographic Information Systems (Gis) In The Study Of Prostate Cancer Disparities: A Systematic Review, Christiane J. El Khoury

Department of Medical Oncology Faculty Papers

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature, and propose alternative approaches. Methods: This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through …

Exposure To Light At Night And Risk Of Cancer: A Systematic Review, Meta-Analysis, And Data Synthesis, Samuel Ma, Yossef Alsabawi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Emerging interest surrounds the role of environmental factors, notably exposure to light at night (LAN), as a potential cause of cancer. The aim of this study was to conduct a systematic review and, if possible, meta-analysis of observational studies on LAN and cancer risk of multiple types.

METHODS: A systematic literature search in PubMed, Web of Science, and Embase, spanning from inception to May 2023, was conducted. Studies focusing on the association between LAN exposure and cancer risk in adult populations were included. We used random effects models to calculate pooled risk estimates (RR) and 95% confidence intervals (CI). …

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 …

Assessing Breast Disease With Deep Learning Model Using Bimodal Bi-View Ultrasound Images And Clinical Information, Fengping Liang, Yihua Song, Xiaoping Huang, Tong Ren, Qiao Ji, Yanan Guo, Xiang Li, Yajuan Sui, Xiaohui Xie, Lanqing Han, Yuanqing Li, Yong Ren, Zuofeng Xu

Faculty, Staff and Students Publications

Breast cancer is the second leading cause of carcinoma-linked death in women. We developed a multi-modal deep-learning model (BreNet) to differentiate breast cancer from benign lesions. BreNet was constructed and trained on 10,108 images from one center and tested on 3,762 images from two centers in three steps. The diagnostic ability of BreNet was first compared with that of six radiologists; a BreNet-aided scheme was constructed to improve the diagnostic ability of the radiologists; and the diagnosis of real-world radiologists' scheme was then compared with the BreNet-aided scheme. The diagnostic performance of BreNet was superior to that of the radiologists …

Central Nervous System Prophylaxis Utilization In Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within A Large Community Health System, Michael J. Williams, Sol D. Atienza, Renee H. Aranda, Kayleigh B. Flint, Sherjeel Sana, Stephen C. Medlin, Zartash Gul, Federico A. Sanchez, Michael A. Thompson

Journal of Patient-Centered Research and Reviews

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score.

Methods: We …