Genetic Phenomena Commons^™

Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth

Faculty, Staff and Student Publications

Purpose: To evaluate the safety and efficacy of vertebral augmentation (VA) and radiofrequency ablation (RFA) for treating pathologic spinal fractures in patients with cancer and adjacent fracture risk following treatment.

Materials and Methods: This single-institution retrospective study, conducted from January 2017 to September 2020, included patients with cancer who underwent percutaneous VA with or without spine RFA for pathologic spine compression fractures. The primary outcome was pain reduction, assessed using the 10-point visual analog scale before the procedure, at first follow-up, and 2–4 weeks after the procedure. Logistic regression was performed to identify factors associated with epidural cement leak.

Results: …

Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet

Faculty, Staff and Student Publications

Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.

Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.

Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes and measures: Oral microbiome …

Defining The Optimal Radiation-Induced Lymphopenia Metric To Discern Its Survival Impact In Esophageal Cancer, Pim J J Damen, Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Purpose: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Methods and materials: Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) …

T2-Weighted Imaging Of Rectal Cancer Using A 3d Fast Spin Echo Sequence With And Without Deep Learning Reconstruction: A Reader Study, Dan Nguyen, Sarah Palmquist, Ken-Pin Hwang, Jingfei Ma, Usama Salem, Jia Sun, Xinzeng Wang, Jong Bum Son, Randy Ernst, Peng Wei, Harmeet Kaur, Nir Stanietzky

Faculty, Staff and Student Publications

Purpose: To compare image quality and clinical utility of a T2-weighted (T2W) 3-dimensional (3D) fast spin echo (FSE) sequence using deep learning reconstruction (DLR) versus conventional reconstruction for rectal magnetic resonance imaging (MRI).

Methods: The study included 50 patients with rectal cancer who underwent rectal MRI consecutively between July 7, 2020 and January 20, 2021 using a T2W 3D FSE sequence with DLR and conventional reconstruction. Three radiologists reviewed the two sets of images, scoring overall SNR, motion artifacts, and overall image quality on a 3-point scale and indicating clinical preference for DLR or conventional reconstruction based on those three …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

Faculty, Staff and Student Publications

Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

Use Of Natural Language Processing To Identify Patients With Inflammatory Breast Cancer Across A Health-Care System, Ramez Kouzy, Megumi Kai, Huong T Le-Petross, Sadia Saleem, Wendy A Woodward

Faculty, Staff and Student Publications

Early identification and referral of inflammatory breast cancer remains challenging within large health-care systems, limiting access to specialized care. We developed and evaluated an artificial intelligence-driven platform integrating natural language processing (NLP) with electronic health records to systematically identify potential inflammatory breast cancer patients across 5 campuses. Our platform analyzed 8 623 494 clinical notes, implementing a sequential review process: NLP screening followed by human validation and multidisciplinary confirmation. Initial NLP screening achieved 55.4% positive predictive value, improving to 78.4% with human-in-the-loop review. Notably, among 255 confirmed patients with inflammatory breast cancer, our system demonstrated 92.2% sensitivity, identifying 57 patients …

Trends In Medicare Payments Within The First Year Of Cervical Cancer Diagnosis, 2010–2019, Mohammad A Karim, Ning Zhang, Hui Zhao, Ya-Chen Tina Shih, Lakshmi S M Kodali, Sharon H Giordano, Sanjay Shete

Faculty, Staff and Student Publications

Assessing Medicare payment trends for cervical cancer care is important to mitigate the financial impact on Medicare. This multiyear cross-sectional study included 65 years and older cervical cancer patients in SEER registries diagnosed between 2010 and 2019 who had continuous Part A and B Medicare coverage at least 6 months before diagnosis and at least within the first year of diagnosis and were not enrolled in any Health Maintenance Organization (HMO) in this duration. The main outcomes were trends in total and service-specific mean monthly Medicare payments within the first year of a cervical cancer diagnosis. This study included 2147 …

Improved Overall Survival In An Anti-Pd-L1 Treated Cohort Of Newly Diagnosed Glioblastoma Patients Is Associated With Distinct Immune, Mutation, And Gut Microbiome Features: A Single Arm Prospective Phase I/Ii Trial, Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V Damania, Mark Knafl, Brian Mckinley, Heather Lin, Rebecca A Harrison, Nazanin K Majd, Barbara J O'Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W K Alfred Yung, Luisa M Solis Soto, Dipen M Maru, Ignacio Wistuba, Edwin R Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A Wargo, Katja Schulze, Walter C Darbonne, Nadim J Ajami, Scott E Woodman, John F De Groot

Faculty, Staff and Student Publications

This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab and TMZ in newly diagnosed glioblastoma (GBM) patients and to identify pre-treatment correlates with outcome (N = 60). Trial number: NCT03174197. The primary outcome was overall survival (OS) whereas secondary outcomes were retrospective global-omics analyses to identify pre-treatment immune and genetic tumor features that correlated with survival. Concurrent use of atezolizumab with radiation and TMZ demonstrated OS in line with published trials for newly diagnosed GBM. Tumor genomic (WES and/or targeted NGS panel), transcriptomic (RNAseq) and tissue microenvironment …

Building A Pre-Surgical Multiparametric-Mri-Based Morphologic, Qualitative, Semiquantitative, First And High-Order Radiomic Predictive Treatment Response Model For Undifferentiated Pleomorphic Sarcoma To Replace Recist, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Robert S Benjamin, Jingfei Ma, Ken-Pin Hwang, R Jason Stafford, Dejka Araujo, Andrew J Bishop, Ravin Ratan, Wei-Lien Wang, Jossue Espinoza, Pia V Valenzuela, Chengyue Wu, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Background: Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response.

Methods: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves …

A Pioneering Artificial Intelligence Tool To Predict Treatment Outcomes In Ovarian Cancer Via Diagnostic Laparoscopy, Xiaotian Ma, Yu-Chun Hsu, Amma Asare, Kai Zhang, Deanna Glassman, Katelyn F Handley, Katherine Foster, Khwahish Sharma, Shannon Westin, Amir Jazaeri, Nicole D Fleming, Pratip K Bhattacharya, Xiaoqian Jiang, Anil K Sood, Shayan Shams

Faculty, Staff and Student Publications

Ovarian cancer is associated with high rates of patient mortality and morbidity. Laparoscopic assessment of tumor localization can be used for treatment planning in newly diagnosed high-grade serous ovarian carcinoma (HGSOC). While spread to multiple intra-abdominal areas is correlated with worse outcomes, whether other morphological tumor differences are also associated with patient outcomes is unknown. Given the large volume of visual information in laparoscopic videos, we investigated whether deep-learning models can capture implicit features and predict treatment outcomes. We developed a novel deep-learning framework using pre-treatment laparoscopic images to assess clinical outcomes following upfront standard treatment, defined as short progression-free …

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Reduced Venetoclax Exposure To 7 Days Vs Standard Exposure With Hypomethylating Agents In Newly Diagnosed Aml Patients, Christophe Willekens, Alexandre Bazinet, Samy Chraibi, Alex Bataller, Justine Decroocq, Naszrin Arani, Benjamin Carpentier, Caitlin Rausch, Delphine Lebon, Abhishek Maiti, Nicolas Gauthier, Nicholas Short, Sarah Bonnet, Koji Sasaki, Sabine Khalife-Hachem, Mahesh Swaminathan, Jean-Baptiste Micol, Florence Pasquier, Christophe Marzac, Damien Roos-Weil, Laurent Pascal, Naval Daver, Tapan Kadia, Didier Bouscary, Farhad Ravandi, Arnaud Pages, Hagop Kantarjian, Stéphane De Botton, Courtney Dinardo

Faculty, Staff and Student Publications

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) …

Kras Mutation Detection By Liquid Biopsy For Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7-4.3, P <  0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Integrated Analysis Of Molecular And Clinical Features Associated With Overall Survival In Melanoma Patients With Brain Metastasis, Swaminathan Kumar, Meredith S Pelster, Merve Hasanov, Renato A Guerrieri, Courtney W Hudgens, Debora A Ledesma, Fuchenchu Wang, Grant M Fischer, Julie M Simon, Lauren E Haydu, Kalman V Katlowitz, Y N Vashisht Gopal, Jennifer L Mcquade, Lawrence N Kwong, Jason T Huse, Alexander J Lazar, Michael T Tetzlaff, Jeffrey E Gershenwald, Aron Y Joon, Ken Chen, Ziyi Li, Prahlad T Ram, Sherise D Ferguson, Michael A Davies

Faculty, Staff and Student Publications

Melanoma brain metastases (MBMs) are diagnosed in up to 60% of metastatic melanoma patients. Previous studies have identified clinical factors that correlate with overall survival (OS) after MBM diagnosis. However, molecular and immune features associated with OS are poorly understood. An improved understanding of the molecular and immune correlates of OS could provide insights into MBM patient outcomes and guide therapeutic development. Thus, we analyzed clinical features and outcomes of 74 melanoma patients who underwent surgical resection (via craniotomy) between 1991 and 2015 at our institution with RNA-seq data generated from their MBMs. The median post-operative OS was 8.6 months …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Her2-Selective Tyrosine Kinase Inhibitor, Zongertinib (Bi 1810631), In Patients With Advanced/Metastatic Solid Tumors With Her2 Alterations: A Phase Ia Dose-Escalation Study, John V Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto

Faculty, Staff and Student Publications

Purpose: Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors.

Materials and methods: Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); …

Phase 2 Trial Of Ibrutinib And Nivolumab In Patients With Relapsed Cns Lymphomas, Dai Chihara, Raphael E Steiner, Ranjit Nair, Lei Feng, Sairah Ahmed, Paolo Strati, Luis Malpica, Donna P Griffith, Shivon A Mathew, Wirt Montinez, Gita Masand, Felipe Samaniego, Maria A Rodriguez, Fredrick B Hagemeister, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Sattva S Neelapu, Christopher R Flowers, Jason R Westin

Faculty, Staff and Student Publications

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years …

A Phase Ii Trial Of Sitravatinib + Nivolumab After Progression On Immune Checkpoint Inhibitor In Patients With Metastatic Clear Cell Rcc, Andrew W Hahn, Nabil Adra, Ulka Vaishampayan, Lianchun Xiao, Nazli Dizman, Ying Yuan, Sagar S Mukhida, Matthew T Campbell, Jianjun Gao, Amado J Zurita, Eric Jonasch, Nizar M Tannir, Amishi Y Shah, Pavlos Msaouel

Faculty, Staff and Student Publications

Background: Sitravatinib, an oral multi-kinase inhibitor targeting VEGFR, TAM, and MET, has been shown to resensitize the tumor microenvironment to immune checkpoint inhibitors (ICI) by reducing immune-suppressive myeloid cells in metastatic clear cell RCC (ccRCC). ICI is the standard first-line (1L) treatment of metastatic ccRCC, and there is unmet need for improved treatment outcomes after progression on ICI. We hypothesized that sitravatinib plus nivolumab would revert an immunosuppressive tumor microenvironment (TME) to improve clinical outcomes.

Methods: In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into 3 …

Long-Term Patient-Reported Bowel And Urinary Quality Of Life In Patients Treated With Intensity-Modulated Radiotherapy Versus Intensity-Modulated Proton Therapy For Localized Prostate Cancer, Kimberly R Gergelis, Miao Bai, Jiasen Ma, David M Routman, Bradley J Stish, Brian J Davis, Thomas M Pisansky, Thomas J Whitaker, Richard Choo

Faculty, Staff and Student Publications

Purpose: This study aimed to compare long-term patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) for localized prostate cancer.

Methods and materials: Patients with clinical T1-T2 prostate cancer receiving IMRT or IMPT at a tertiary cancer center from 2015-2018 were analyzed to determine the changes in the prospectively collected bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26. The mean changes in EPIC-26 scores were evaluated from pretreatment to 24 months post-radiotherapy for each modality. A score change >50% of the baseline standard deviation was considered a …

Diet And Survival After A Diagnosis Of Ovarian Cancer: A Pooled Analysis From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Renhua Na, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice Lee, Valerie Mcguire, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Joellen M Schildkraut, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm C Pike, Celeste Leigh Pearce, Penelope M Webb, Multidisciplinary Ovarian Cancer Outcomes Group And Ovarian Cancer Association Consortium

Faculty, Staff and Student Publications

Background: Prognosis after a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent.

Objectives: This study aims to pool data from studies conducted around the world to evaluate the relationships among dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer.

Methods: This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their prediagnosis diet. Adjusted hazard ratios (aHRs) …

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Micah J Marshall, Chelsea Caspell-Garcia, Michael C Brumm, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Receptor Tyrosine Kinase Fusion-Mediated Resistance To Egfr Tki In Egfr-Mutant Nsclc: A Multi-Center Analysis And Literature Review, Yang Xia, Kaiwen Wang, Jing Zhao, Zhaohui Arter, Yongchang Zhang, Jiaqi Zhou, Yuefei Lu, Liang Zeng, Robyn Du, Jennifer A Owens, Yasir Y Elamin, Carl M Gay, Ferdinandos Skoulidis, Anne S Tsao, Charles Lu, Tina Cascone, Don L Gibbons, Jianjun Zhang, Olivia Chen, Kevin K S Mok, Misako Nagasaka, Wen Li, John V Heymach, Sai-Hong Ignatius Ou, Molly Li, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Drug resistance remains a major clinical challenge in EGFR-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition.

Methods: We queried clinical databases from multiple institutions to identify patients who had RTK fusions detected on next-generation sequencing testing results from …

Efficacy And Safety Of Denileukin Diftitox-Cxdl, An Improved Purity Formulation Of Denileukin Diftitox, In Patients With Relapsed Or Refractory Cutaneous T-Cell Lymphoma, Francine M Foss, Youn H Kim, H Miles Prince, Oleg E Akilov, Christiane Querfeld, Lucia Seminario-Vidal, David C Fisher, Timothy M Kuzel, Costas K Yannakou, Larisa J Geskin, Tatyana Feldman, Lubomir Sokol, Pamela Blair Allen, Nam Hoang Dang, Fernando Cabanillas, Henry K Wong, Chean Eng Ooi, Dongyuan Xing, Nicholas Sauter, Preeti Singh, Myron Czuczman, Madeleine Duvic

Faculty, Staff and Student Publications

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. …