Biomedical Informatics Commons^™

Predicting Sinonasal Inverted Papilloma Attachment Using Machine Learning: Current Lessons And Future Directions, Sean P Mckee, Xiaomin Liang, William C Yao, Brady Anderson, Jumah G Ahmad, David Z Allen, Salman Hasan, Andy J Chua, Chinmay Mokashi, Samia Islam, Amber U Luong, Martin J Citardi, Luca Giancardo

Faculty, Staff and Student Publications

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed. The tumor attachment site was manually segmented on CT scans by the operating surgeon. We used a nnU-Net model, a state-of-the-art deep learning-based segmentation algorithm that automatically configures image preprocessing, network architecture, training, and post-processing to identify the IP attachment site. The model was trained and evaluated using a 5-fold cross …

Empathy Unmasked: Patient Perception Of Physician Empathy In An Oncologic Emergency Setting A Randomized Controlled Trial Comparing Personal Protective Equipment Wear Versus Unmasked Video Communication, Kathryn J Burk, John J Stroh, Kelly Larkin, Patrick Chaftari, Denise M Langabeer, Jazmin R Menendez, Jeanie F Woodruff, Jan Hargrave, Hongxu Zhu, James P Long, Sai-Ching J Yeung, Kumar Alagappan, Aiham Qdaisat

Faculty, Staff and Student Publications

Background: Amidst the COVID-19 pandemic, telemedicine emerged as an important option that supports and facilitates clinical practice, however, its usefulness in emergency settings that treat patients with cancer is unclear.

Objective: To evaluate patient perception of physician empathy in an emergency oncology setting, comparing video interaction to an in-person with personal protective equipment (PPE) approach.

Methods: In this single-center, prospective, cross-sectional, survey-based randomized controlled trial, patients were randomized 1:1 for the concluding conversation done in-person which included either interacting with physicians wearing PPE or video interaction with physicians without PPE (virtual). Patients' perceptions of the physicians' relational empathy were assessed …

Weighted Hypoxemia Index: An Adaptable Method For Quantifying Hypoxemia Severity, Diane C Lim, Cheng-Bang Chen, Ankita Paul, Yujie Wang, Jinyoung Kim, Soonhyun Yook, Emily Y Kim, Edison Q Kim, Anup Das, Medhi Wangpaichitr, Virend K Somers, Chi Hang Lee, Phyllis C Zee, Toshihiro Imamura, Hosung Kim

Faculty, Staff and Student Publications

Objective: To quantitate hypoxemia severity.

Methods: We developed the Weighted Hypoxemia Index to be adapted to different clinical settings by applying 5 steps to the oxygen saturation curve: (1) Identify desaturation/resaturation event [Formula: see text] by setting the upper threshold; (2) Exclude events as artifact by setting a lower threshold; (3) Calculate weighted area for each [Formula: see text] as [Formula: see text]; (4) Calculate a normalization factor [Formula: see text] for each subject; (5) Calculate the Weighted Hypoxemia Index as the summation of all weighted areas multiplied by [Formula: see text]. We assessed the Weighted Hypoxemia Index predictive value …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Epidemiology Of Patient Record Duplication, Onur Sahin, Audrey Zhao, Reuben Joseph Applegate, Todd R Johnson, Elmer V Bernstam

Faculty, Staff and Student Publications

Objectives: Duplicate patient records can increase costs and medical errors. We assessed the association between demographic factors, comorbidities, health care usage, and duplicate electronic health records.

Methods: We analyzed the association between duplicate patient records and multiple demographic variables (race, Hispanic ethnicity, sex, and age) as well as the Charlson Comorbidity Index (CCI), number of diagnoses, and number of health care encounters. The study population included 3,018,413 patients seen at a large urban academic medical center with at least one recorded diagnosis. Duplication of patient medical records was determined by using a previously validated enterprise Master Person Index.

Results: Unknown …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ella Ariza-Heredia, Ying Jiang, Roy F Chemaly

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

Disparities In Breast Cancer Detection Modalities And Outcomes Among Geriatric Female Cancer Patients, Zhaoli Liu, Mathilda Nicot-Cartsonis, Biai D E Digbeu, Daoqi Gao, Sharon H Giordano, Yong-Fang Kuo

Faculty, Staff and Student Publications

This study examined racial and geographic disparities in breast cancer detection modalities (screening-, diagnostic-, or non-mammography) with cancer stage and mortality. A retrospective cohort study was conducted using Texas Cancer Registry-Medicare linkage data for geriatric women. Cancers detected through screening and diagnostic mammography had 43 % (95 % CI, 39 %-46 %, p < .0001) and 31 % (95 % CI, 27 %-35 %, p < .0001) lower all-cause mortality, and 49 % (95 % CI, 41 %-54 %, p < .0001) and 37 % (95 % CI, 32 %-43 %, p < .0001) lower cancer-specific mortality, respectively, compared to non-mammography-detected breast cancers. Patients from rural areas were 17 % (95 % CI, 1.06 - 1.29) more likely to be diagnosed with mid- (p = .0023) and advanced stage (p = .003) cancers compared to their urban counterparts. Racial or geographic disparities in cancer detection modalities with associated mortality no longer exist after adjusting for covariates. Healthcare professionals can leverage these findings to promote rural cancer health equity.

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Faculty, Staff and Student Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Survival Analysis Of Clear Cell Renal Cell Carcinoma Based On Radiomics And Deep Learning Features From Ct Images, Zhennan Lu, Sijia Wu, Dan Ni, Meng Zhou, Tao Wang, Xiaobo Zhou, Liyu Huang, Yu Yan

Faculty, Staff and Student Publications

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator. Then the selected features formed a fusion signature, which was assessed by Cox proportional hazard regression model method, Kaplan-Meier analysis, receiver operating characteristic curves, and concordance index (C-index) …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

Transcriptomic Clustering Of Chronic Lymphocytic Leukemia: Molecular Subtypes Based On Bruton’S Tyrosine Kinase Expression Levels, Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L Ayres, Lakesla R Iles, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples …

Clinical Use Of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging In Patients On Extracorporeal Membrane Oxygenation: Results From The Multicenter Safe Mri Ecmo Study, Sung-Min Cho, Shivalika Khanduja, Christopher Wilcox, Kha Dinh, Jiah Kim, Jin Kook Kang, Ifeanyi David Chinedozi, Zachary Darby, Matthew Acton, Hannah Rando, Jessica Briscoe, Errol L Bush, Haris I Sair, John Pitts, Lori R Arlinghaus, Audrey-Carelle N Wandji, Elena Moreno, Glenda Torres, Bindu Akkanti, Jose Gavito-Higuera, Steven Keller, Huimahn A Choi, Bo Soo Kim, Aaron Gusdon, Glenn J Whitman

Faculty, Staff and Student Publications

Background: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI.

Methods: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive …

Automated Segmentation Of Mri White Matter Hyperintensities In 8421 Patients With Acute Ischemic Stroke, Hosung Kim, Wi-Sun Ryu, Dawid Schellingerhout, Jonghyeok Park, Jinyong Chung, Sang-Wuk Jeong, Dong-Seok Gwak, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyung Bok Lee, Tai Hwan Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Man Seok Park, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

Background and purpose: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction; this issue is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction using multisite data sets involving 8421 patients with acute ischemic stroke.

Materials and methods: We included 8421 patients with stroke from 9 centers in Korea. 2D UNet and squeeze-and-excitation (SE)-UNet models were trained using 2408 FLAIR MRIs from 3 hospitals and validated using 6013 FLAIR …

Integrative Multi-Omics Analysis Uncovers Tumor-Immune-Gut Axis Influencing Immunotherapy Outcomes In Ovarian Cancer, Spencer R Rosario, Mark D Long, Shanmuga Chilakapati, Eduardo Cortes Gomez, Sebastiano Battaglia, Prashant K Singh, Jianmin Wang, Katy Wang, Kristopher Attwood, Suzanne M Hess, A J Robert Mcgray, Kunle Odunsi, Brahm H Segal, Gyorgy Paragh, Song Liu, Jennifer A Wargo, Emese Zsiros

Faculty, Staff and Student Publications

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We …

Clonal Landscape And Clinical Outcomes Of Telomere Biology Disorders: Somatic Rescue And Cancer Mutations, Fernanda Gutierrez-Rodrigues, Emma M Groarke, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Luiz Fernando B Catto, Marena R Niewisch, Ruba Shalhoub, Lisa J Mcreynolds, Diego V Clé, Bhavisha A Patel, Xiaoyang Ma, Dalton Hironaka, Flávia S Donaires, Nina Spitofsky, Barbara A Santana, Tsung-Po Lai, Lemlem Alemu, Sachiko Kajigaya, Ivana Darden, Weiyin Zhou, Paul V Browne, Subrata Paul, Justin Lack, David J Young, Courtney D Dinardo, Abraham Aviv, Feiyang Ma, Michel Michels De Oliveira, Ana Paula De Azambuja, Cynthia E Dunbar, Malgorzata Olszewska, Emmanuel Olivier, Eirini P Papapetrou, Neelam Giri, Blanche P Alter, Carmem Bonfim, Colin O Wu, Guillermo Garcia-Manero, Sharon A Savage, Neal S Young, Simona Colla, Rodrigo T Calado

Faculty, Staff and Student Publications

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, …

Diet And Immune Effects Trial (Diet)- A Randomized, Double-Blinded Dietary Intervention Study In Patients With Melanoma Receiving Immunotherapy, Rachel M Farias, Yan Jiang, Erma J Levy, Cindy Hwang, Jian Wang, Elizabeth M Burton, Lorenzo Cohen, Nadim Ajami, Jennifer A Wargo, Carrie R Daniel, Jennifer L Mcquade

Faculty, Staff and Student Publications

Background: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and …

Trajectory, Interactions, And Predictors Of Higher Symptom Burden During Induction Therapy For Multiple Myeloma, Mona Kamal, Qiuling Shi, Shu-En Shen, Charles Cleeland, Xin Shelley Wang

Faculty, Staff and Student Publications

Background: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus …

Private-Sector Readmissions For Inpatient Surgery In Veterans Health Administration Hospitals, Mary Vaughan Sarrazin, Yubo Gao, Carly A Jacobs, Michael A Jacobs, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Andrea L Strayer, John Cashy, George Wehby, Paula K Shireman, Daniel E Hall

Faculty, Staff and Student Publications

Importance: The Veterans Health Administration (VHA) reports multiple indicators of hospital surgical performance, including hospital risk-standardized 30-day readmission rates (RSRRs). Currently, most routinely reported measures do not include readmissions that occur outside VHA hospitals. The impact of readmissions outside the VHA on hospital RSRR is not known.

Objective: To measure the impact of including non-VHA readmissions on VHA hospital performance rankings for 30-day readmission.

Design, setting, and participants: This retrospective cohort study included patients aged at least 65 years from 2013 to 2019 from the Veterans Affairs Surgical Quality Improvement Program linked to patient-level data from the VHA and Medicare. …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …

High Activity Of The New Myeloablative Regimen Of Gemcitabine/Clofarabine/Busulfan For Allogeneic Transplant For Aggressive Lymphomas, Jeremy Ramdial, Ruitao Lin, Peter F Thall, Benigno C Valdez, Chitra Hosing, Samer Srour, Uday Popat, Muzaffar Qazilbash, Amin Alousi, Melissa Barnett, Alison Gulbis, Terri Lynn Shigle, Elizabeth J Shpall, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically. Eligibility: age 12-65, refractory aggressive B-NHL, T-NHL or Hodgkin, with a matched donor. Infusional Gem was dose-escalated on days (d) -6 and -4 (475-975 mg/m2/day), followed by Clo (40 mg/m2/day) and Bu (target AUC, 4000 μMol min/day) (d -6 to -3). CD20+ tumors received rituximab. GVHD prophylaxis …

Anti-Programmed Death Ligand 1 Plus Targeted Therapy In Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial, Maria E Cabanillas, Ramona Dadu, Renata Ferrarotto, Maria Gule-Monroe, Suyu Liu, Bryan Fellman, Michelle D Williams, Mark Zafereo, Jennifer R Wang, Charles Lu, Matthew Ning, Brian A Mckinley, Scott E Woodman, Dzifa Duose, Gary B Gunn, Naifa L Busaidy, Rare Tumor Initiative Team

Faculty, Staff and Student Publications

Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.

Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).

Design, setting, and participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus …

Association Between Socioeconomic Disadvantage And Risks Of Early And Recurrent Admissions Among Patients With Newly Diagnosed Heart Failure, Radha Dhingra, Hanzhang Xu, Bradley G Hammill, Scott M Lynch, Jessica S West, Michael D Green, Eric D Peterson, Lesley H Curtis, Matthew E Dupre

Faculty, Staff and Student Publications

Background: Socioeconomic disadvantage is associated with greater risks of hospital readmission and mortality among patients with heart failure (HF). However, it is less clear whether socioeconomic disadvantage has an immediate and lasting impact on the risk of admissions after the diagnosis of HF.

Methods: We used electronic health record data of patients aged 65 years and older with newly diagnosed HF between January 2015 and July 2018 in the Duke University Health System, with up to 8 years of follow-up. We assessed the association between neighborhood-level disadvantage, measured by the area deprivation index (lower, moderate, or higher) and hospital admissions …