Medical Genetics Commons^™

Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 Years, Gypsyamber D'Souza, Sakshi R Tewari, Tanya Troy, Jennifer Webster-Cyriaque, Dorothy J Wiley, Cecile Delille Lahiri, Frank Joseph Palella, Maura L Gillison, Howard D Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M Weber, Carole Fakhry

Faculty, Staff and Student Publications

Background: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.

Methods: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).

Results: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but …

Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉

Faculty, Staff and Students Publications

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as …

Author Correction: Automating Data Analysis For Hydrogen/Deuterium Exchange Mass Spectrometry Using Data-Independent Acquisition Methodology, Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D Alex Crowder, Morgan F Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A Tainer, Susan P Lees-Miller, David C Schriemer

Faculty, Staff and Student Publications

No abstract provided.

Social And Behavior Factors Of Alzheimer's Disease And Related Dementias: A National Study In The Us, David Ciciora, Elizabeth Vásquez, Edward Valachovic, Lifang Hou, Yinan Zheng, Hua Xu, Xiaoqian Jiang, Kun Huang, Kelley Pettee Gabriel, Hong-Wen Deng, Mary P Gallant, Kai Zhang

Faculty, Staff and Student Publications

Introduction: Considerable research has linked many risk factors to Alzheimer's Disease and Related Dementias (ADRD). Without a clear etiology of ADRD, it is advantageous to rank the known risk factors by their importance and determine if disparities exist. Statistical-based ranking can provide insight into which risk factors should be further evaluated.

Methods: This observational, population-based study assessed 50 county-level measures and estimates related to ADRD in 3,155 counties in the U.S. using data from 2010 to 2021. Statistical analysis was performed in 2022-2023. The machine learning method, eXtreme Gradient Boosting, was utilized to rank the importance of these variables by …

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Premastectomy Radiotherapy And Immediate Breast Reconstruction: A Randomized Clinical Trial, Mark V Schaverien, Puneet Singh, Benjamin D Smith, Wei Qiao, Catherine L Akay, Elizabeth S Bloom, Mariana Chavez-Macgregor, Carrie K Chu, Mark W Clemens, Jessica S Colen, Richard A Ehlers, Rosa F Hwang, Melissa M Joyner, Rene D Largo, Alexander F Mericli, Melissa P Mitchell, John W Shuck, Nina Tamirisa, Debasish Tripathy, Mark T Villa, Wendy A Woodward, Rensi Zacharia, Henry M Kuerer, Karen E Hoffman

Faculty, Staff and Student Publications

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

The Tudor-Knot Domain Of Kat5 Regulates Nucleosomal Substrate Acetylation, Fan Xuan, Hongwen Xuan, Mengying Huang, Wei He, Han Xu, Xiaobing Shi, Hong Wen

Faculty, Staff and Student Publications

The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in …

Flexible Bayesian Product Mixture Models For Vector Autoregressions, Suprateek Kundu, Joshua Lukemire

Faculty, Staff and Student Publications

Bayesian non-parametric methods based on Dirichlet process mixtures have seen tremendous success in various domains and are appealing in being able to borrow information by clustering samples that share identical parameters. However, such methods can face hurdles in heterogeneous settings where objects are expected to cluster only along a subset of axes or where clusters of samples share only a subset of identical parameters. We overcome such limitations by developing a novel class of product of Dirichlet process location-scale mixtures that enables independent clustering at multiple scales, which results in varying levels of information sharing across samples. First, we develop …

Fear Antiviral Response Pathway Is Independent Of Interferons And Countered By Poxvirus Proteins, Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger, Neal M Alto, Flávio Guimarães Da Fonseca, Robert Orchard, Dustin C Hancks, Don B Gammon

Faculty, Staff and Student Publications

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 …

Delta Radiomic Features Predict Resection Margin Status And Overall Survival In Neoadjuvant-Treated Pancreatic Cancer Patients, Kai Wang, John D Karalis, Ahmed Elamir, Alessandro Bifolco, Megan Wachsmann, Giovanni Capretti, Paola Spaggiari, Sebastian Enrico, Kishore Balasubramanian, Nafeesah Fatimah, Giada Pontecorvi, Martina Nebbia, Adam Yopp, Ravi Kaza, Ivan Pedrosa, Herbert Zeh, Patricio Polanco, Alessandro Zerbi, Jing Wang, Todd Aguilera, Matteo Ligorio

Faculty, Staff and Student Publications

Background: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions.

Methods: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). …

Recurrent Lymphoid And Myeloid Relapses Due To Treatment Cessations Reveal Natural History Of Ph-Positive B-All And Pose A Diagnostic Challenge, Shimin Hu, Elias J Jabbour, Collin Y Hu, Guilin Tang, Wei Wang, L Jeffrey Medeiros, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

No abstract provided.

Bone Marrow-Restricted Aberrant Myeloperoxidase Expression In B-Acute Lymphoblastic Leukemia: A Diagnostic Dilemma And Mimicry Of Mixed Phenotype Acute Leukemia, Wei J Wang, Brandon T Gehris, Daniel Rivera, Sibel Ak, David Feng, Wei Wang, Zhihong Hu

Faculty, Staff and Student Publications

Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B-acute lymphoblastic leukemia (B-ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review. Furthermore, we emphasize the necessity of conducting a comprehensive analysis for the accurate diagnosis of MPO-positive B-ALL cases.

Diagnostic Utility Of Immunohistochemistry In Detection Of Npm1 Mutations In Acute Myeloid Leukemia With A Patchy Distribution, Qing Wei, Sa A Wang, Sanam Loghavi, Hong Fang, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

Nucleophosmin 1 (NPM1) mutations occur in approximately one‐third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Alk-Positive Histiocytosis Of External Auditory Canal In A 3-Year-Old Boy, Shu-Hsien Wang, Hsuan-Ying Huang, L Jeffrey Medeiros, Kung-Chao Chang

Faculty, Staff and Student Publications

No abstract provided.

Socioeconomic Status And Chronic Health Conditions In Asian Survivors Of Adolescent And Young Adult Cancers, Amy M Berkman, Eunju Choi, Christabel K Cheung, John M Salsman, Susan K Peterson, Clark R Andersen, Qian Lu, J Andrew Livingston, Michelle A T Hildebrandt, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Purpose: While there are known disparities in socioeconomic status (SES) and health outcomes among racially and ethnically minoritized adolescent and young adult (AYA; ages 15-39 years at diagnosis) cancer survivors compared with White survivors, outcomes in the Asian survivor population are understudied. To better understand the association of an AYA cancer diagnosis with SES and health outcomes within a minoritized population, the current study makes comparisons between individuals of the same race or ethnicity with and without a history of AYA cancer.

Methods: Non-Hispanic, Asian AYA cancer survivors and non-Hispanic, Asian age- and sex-matched controls were identified from self-reported data …

Temporal Changes In Treatment And Late Mortality And Morbidity In Adult Survivors Of Childhood Glioma: A Report From The Childhood Cancer Survivor Study, Peter M K De Blank, Katharine R Lange, Mengqi Xing, Sedigheh Mirzaei Salehabadi, Deokumar Srivastava, Tara M Brinkman, Kirsten K Ness, Kevin C Oeffinger, Joseph Neglia, Kevin R Krull, Paul C Nathan, Rebecca Howell, Lucie M Turcotte, Wendy Leisenring, Gregory T Armstrong, M Fatih Okcu, Daniel C Bowers

Faculty, Staff and Student Publications

Pediatric glioma therapy has evolved to delay or eliminate radiation for low-grade tumors. This study examined these temporal changes in therapy with long-term outcomes in adult survivors of childhood glioma. Among 2,501 5-year survivors of glioma in the Childhood Cancer Survivor Study diagnosed 1970-1999, exposure to radiation decreased over time. Survivors from more recent eras were at lower risk of late mortality (≥5 years from diagnosis), severe/disabling/life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs). Adjusting for treatment exposure (surgery only, chemotherapy, or any cranial radiation) attenuated this risk (for example, CHCs (1990s versus 1970s), relative risk (95% confidence interval), …

Survival Outcomes And Toxicity Of Adjuvant Immunotherapy After Definitive Concurrent Chemotherapy With Proton Beam Radiation Therapy For Patients With Inoperable Locally Advanced Non-Small Cell Lung Carcinoma, Kelsey L Corrigan, Ting Xu, Yuki Sasaki, Ruitao Lin, Aileen B Chen, James W Welsh, Steven H Lin, Joe Y Chang, Matthew S Ning, Saumil Gandhi, Michael S O'Reilly, Carl M Gay, Mehmet Altan, Charles Lu, Tina Cascone, Efstratios Koutroumpakis, Ajay Sheshadri, Xiaodong Zhang, Li Liao, X Ronald Zhu, John V Heymach, Quynh-Nhu Nguyen, Zhongxing Liao

Faculty, Staff and Student Publications

Introduction: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC.

Materials and methods: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated …

Loss-Of-Function Mutation In Prmt9 Causes Abnormal Synapse Development By Dysregulation Of Rna Alternative Splicing, Lei Shen, Xiaokuang Ma, Yuanyuan Wang, Zhihao Wang, Yi Zhang, Hoang Quoc Hai Pham, Xiaoqun Tao, Yuehua Cui, Jing Wei, Dimitri Lin, Tharindumala Abeywanada, Swanand Hardikar, Levon Halabelian, Noah Smith, Taiping Chen, Dalia Barsyte-Lovejoy, Shenfeng Qiu, Yi Xing, Yanzhong Yang

Faculty, Staff and Student Publications

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between …

Oral Decitabine And Cedazuridine Plus Venetoclax For Older Or Unfit Patients With Acute Myeloid Leukaemia: A Phase 2 Study, Alexandre Bazinet, Guillermo Garcia-Manero, Nicholas Short, Yesid Alvarado, Alex Bataller, Tareq Abuasab, Rabiul Islam, Kathryn Montalbano, Ghayas Issa, Abhishek Maiti, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Guillermo Montalban-Bravo, Caitlin R Rausch, Sherry Pierce, Courtney D Dinardo, Tapan Kadia, Naval Daver, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax.

Methods: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. …

Trajectories Of Health Care Contact Days For Patients With Stage Iv Non-Small Cell Lung Cancer, Arjun Gupta, Paul Nguyen, Danielle Kain, Andrew G Robinson, Amit A Kulkarni, David H Johnson, Carolyn J Presley, Anne H Blaes, Gabrielle B Rocque, Ishani Ganguli, Christopher M Booth, Timothy P Hanna

Faculty, Staff and Student Publications

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC.

Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice.

Design, setting, and participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 …

Author Correction: An Atlas Of Epithelial Cell States And Plasticity In Lung Adenocarcinoma, Guangchun Han, Ansam Sinjab, Zahraa Rahal, Anne M Lynch, Warapen Treekitkarnmongkol, Yuejiang Liu, Alejandra G Serrano, Jiping Feng, Ke Liang, Khaja Khan, Wei Lu, Sharia D Hernandez, Yunhe Liu, Xuanye Cao, Enyu Dai, Guangsheng Pei, Jian Hu, Camille Abaya, Lorena I Gomez-Bolanos, Fuduan Peng, Minyue Chen, Edwin R Parra, Tina Cascone, Boris Sepesi, Seyed Javad Moghaddam, Paul Scheet, Marcelo V Negrao, John V Heymach, Mingyao Li, Steven M Dubinett, Christopher S Stevenson, Avrum E Spira, Junya Fujimoto, Luisa M Solis, Ignacio I Wistuba, Jichao Chen, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

No abstract provided.

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Clinical Management, Monitoring, And Prophylaxis Of Adverse Events Of Special Interest Associated With Datopotamab Deruxtecan, Rebecca S Heist, Jacob Sands, Aditya Bardia, Toshio Shimizu, Aaron Lisberg, Ian Krop, Noboru Yamamoto, Takahiro Kogawa, Saba Al-Hashimi, Simon S M Fung, Anat Galor, Francesca Pisetzky, Priyanka Basak, Cindy Lau, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in …

Surgical Outcomes After Chemotherapy Plus Nivolumab And Chemotherapy Plus Nivolumab And Ipilimumab In Patients With Non-Small Cell Lung Cancer, Hope Feldman, Boris Sepesi, Cheuk H Leung, Heather Lin, Annikka Weissferdt, Apar Pataer, William N William, Garrett L Walsh, David C Rice, Jack A Roth, Reza J Mehran, Wayne L Hofstetter, Mara B Antonoff, Ravi Rajaram, Don L Gibbons, J Jack Lee, John V Heymach, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone

Faculty, Staff and Student Publications

Objective: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab.

Methods: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab …

Neuroendocrine Neoplasms Of The Ovary: A Review Of 63 Cases, Alejandra Flores Legarreta, Reem Saab, Naomi R Gonzales, Gary B Chisholm, Shannon N Westin, R Tyler Hillman, Michael Frumovitz

Faculty, Staff and Student Publications

Objective: To describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry.

Methods: This is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine neoplasms. We excluded patients with small cell carcinoma not otherwise specified, small cell hypercalcemic type, and those with neuroendocrine 'features' or 'differentiation.' Clinicopathological characteristics were described in two separate groups: patients with carcinoid tumors and patients with neuroendocrine carcinomas. Progression-free and overall survival were estimated with the Kaplan-Meier product-limit estimator in these two groups, and multivariable analysis was done to identify predictors of survival for neuroendocrine carcinomas …

Cytogenetic And Molecular Associations With Outcomes In Higher-Risk Myelodysplastic Syndromes Treated With Hypomethylating Agents Plus Venetoclax, Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M Kadia, Gautam Borthakur, Courtney D Dinardo, Naval G Daver, Elias J Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood.

Experimental design: We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations …

Analysis Of Microbiome Data, Christine B Peterson, Satabdi Saha, Kim-Anh Do

Faculty, Staff and Student Publications

The microbiome represents a hidden world of tiny organisms populating not only our surroundings but also our own bodies. By enabling comprehensive profiling of these invisible creatures, modern genomic sequencing tools have given us an unprecedented ability to characterize these populations and uncover their outsize impact on our environment and health. Statistical analysis of microbiome data is critical to infer patterns from the observed abundances. The application and development of analytical methods in this area require careful consideration of the unique aspects of microbiome profiles. We begin this review with a brief overview of microbiome data collection and processing and …

Prognostic Value Of Tumor Volume Doubling Time In Lung-Metastatic Adenoid Cystic Carcinoma, Eduardo A Dal Lago, Luana G Sousa, Zixi Yang, Camilla O Hoff, Flavia Bonini, Matthew Sawyer, Kaiwen Wang, Whitney Lewis, Kareem A Wahid, Ehab Y Hanna, Adel El-Naggar, Clifton D Fuller, Suprateek Kundu, Myrna Godoy, Renata Ferrarotto

Faculty, Staff and Student Publications

Objectives: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT).

Methods: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), …

Exploring Ferroptosis-Inducing Therapies For Cancer Treatment: Challenges And Opportunities, Guang Lei, Boyi Gan

Faculty, Staff and Student Publications

Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis-an iron-dependent regulated cell death triggered by lipid peroxide accumulation-has gained prominence in cancer research in recent years. Ferroptosis-inducing therapies hold promise for overcoming resistance encountered with conventional treatments. However, challenges, including the lack of distinctive ferroptosis markers and the intricate role of ferroptosis within the tumor microenvironment, currently hinder the clinical translation of these therapies. This perspective article critically outlines these hurdles and highlights …