Life Sciences Commons^™

Plain Language Summary Of The Foenix-Cca2 Study: Futibatinib For People With Advanced Bile Duct Cancer, Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W Valle, Chigusa Morizane, Thomas B Karasic, Thomas A Abrams, Junji Furuse, Robin Katie Kelley, Philippe A Cassier, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Yoshito Komatsu, Daniel H Ahn, Robert S Epstein, Abdel-Baset Halim, Volker Wacheck, Yaohua He, Mei Liu, Karim A Benhadji, John A Bridgewater, Foenix-Cca2 Study Investigators

Faculty, Staff and Student Publications

What is this summary about?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their …

Impact Of P53-Associated Acute Myeloid Leukemia Hallmarks On Metabolism And The Immune Environment, Monika Chomczyk, Luca Gazzola, Shubhankar Dash, Patryk Firmanty, Binsah S George, Vakul Mohanty, Hussein A Abbas, Natalia Baran

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML …

Rural Racial Disparities And Barriers In Mammography Utilization Among Medicare Beneficiaries In Texas: A Longitudinal Study, Zhaoli Liu, Yong Shan, Yong-Fang Kuo, Sharon H Giordano

Faculty, Staff and Student Publications

This study examined rural racial/ethnic disparities in long-term mammography screening practices among Medicare beneficiaries. A retrospective longitudinal study was conducted using 100% Texas Medicare data for women aged 65-74 who enrolled in Medicare between 2010-2013. Of the 114,939 eligible women, 21.2% of Hispanics, 33.3% of non-Hispanic Blacks (NHB), and 38.4% non-Hispanic Whites (NHW) in rural areas were regular users of mammography, compared to 33.5%, 44.9%, and 45.3% of their counterparts in urban areas, respectively. Stratification analyses showed rural Hispanics and NHB were 33% (95% CI, 25% - 40%) and 22% (95% CI, 6% - 36%) less likely to be regular …

Screening For Food And Nutrition Insecurity In The Healthcare Setting: A Cross-Sectional Survey Of Non-Medicaid Insured Adults In An Integrated Healthcare Delivery System, Carmen Byker Shanks, Nancy P Gordon

Faculty, Staff and Student Publications

OBJECTIVES: Healthcare screening identifies factors that impact patient health and well-being. Hunger as a Vital Sign (HVS) is widely applied as a screening tool to assess food security. However, there are no common practice screening questions to identify patients who are nutrition insecure or acquire free food from community-based organizations. This study used self-reported survey data from a non-Medicaid insured adult population approximately one year after the start of the COVID-19 pandemic (2021). The survey examined the extent to which the HVS measure might have under-estimated population-level food insecurity and/or nutrition insecurity, as well as under-identified food and nutrition insecurity …

A Brief But Comprehensive Three-Item Social Connectedness Screener For Use In Social Risk Assessment Tools, Nancy P Gordon, Matthiew C Stiefel

Faculty, Staff and Student Publications

BACKGROUND: The 2014 IOM report "Capturing Social and Behavioral Domains and Measures in Electronic Health Records" described three subdomains of social relationships that affect patient health and well-being. However, most social risk screeners currently assess only one subdomain, frequency of social connections. We are proposing a three-item Brief Social Connectedness (SC) screener that additionally assesses risks in social/emotional support and loneliness/social isolation subdomains.

METHODS: For this cross-sectional study, we used data from a 2021 Kaiser Permanente Northern California (KPNC) social risk survey for 2244 members ages 35-85 years. The survey included three validated questions that covered the SC subdomains (frequencies …

Healthcare Resource Utilization, Costs And Treatment Associated With Myasthenia Gravis Exacerbations Among Patients With Myasthenia Gravis In The Usa: A Retrospective Analysis Of Claims Data, Julia Pisc, Angela Ting, Michelle Skornicki, Omar Sinno, Edward Lee

Faculty, Staff and Student Publications

Aim: There are limited data on the clinical and economic burden of exacerbations in patients with myasthenia gravis (MG). We assessed patient clinical characteristics, treatments and healthcare resource utilization (HCRU) associated with MG exacerbation. Patients & methods: This was a retrospective analysis of adult patients with MG identified by commercial, Medicare or Medicaid insurance claims from the IBM® MarketScan® database. Eligible patients had two or more MG diagnosis codes, without evidence of exacerbation or crisis in the baseline period (12 months prior to index [first eligible MG diagnosis]). Clinical characteristics were evaluated at baseline and 12 weeks before each exacerbation. …

Association Between Symptom Burden And Early Lymphatic Abnormalities After Regional Nodal Irradiation For Breast Cancer, Alison K Yoder, Tianlin Xu, Peter Youssef, Sarah Desnyder, Kathryn E Marqueen, Lynn Isales, Ruitao Lin, Benjamin D Smith, Wendy A Woodward, Michael C Stauder, Eric A Strom, Melissa B Aldrich, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRF-LI) signals preclinical lymphedema that precedes the development of volumetrically defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI).

METHODS AND MATERIALS: Patients with breast cancer planned for axillary dissection and RNI prospectively underwent perometry, NIRF-LI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey [LSIDS] and QuickDASH) at baseline, after surgery, and at 6, 12, and 18 months after radiation. Clinical lymphedema was defined as an arm volume increase ≥5% over baseline. Trends …

Effect Of S-Ketamine On Postoperative Nausea And Vomiting In Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial, Yu Qi, Meiyan Zhou, Wenting Zheng, Yaqi Dong, Weihua Li, Long Wang, Haijun Xu, Miao Zhang, Dunpeng Yang, Liwei Wang, Hai Zhou

Faculty, Staff and Student Publications

PURPOSE: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy.

PATIENTS AND METHODS: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine …

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …

Stereotactic Body Radiation Therapy For Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review, Colton Ladbury, Mark H Sueyoshi, Nellie M Brovold, Ritesh Kumar, Therese Y Andraos, Emile Gogineni, Minsun Kim, Ann Klopp, Kevin Albuquerque, Charles Kunos, Eric Leung, Constantine Mantz, Tithi Biswas, Sushil Beriwal, William Small, Beth Erickson, David Gaffney, Simon S Lo, Akila N Viswanathan

Faculty, Staff and Student Publications

Purpose: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients.

Methods and materials: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

RESULTS: One hundred ninety-two patients had a median follow-up of 82 …

Multifactorial Exercise Intervention Decreases Falls Risk In High-Risk And Low-Risk Older Adults, Amanda Estep, Steven Morrison, Shane V. Caswell, Jatin P. Ambegaonkar, João R. Vaz, Nelson Cortes

Rehabilitation Sciences Faculty Publications

Background: Each year, 1 in 4 people over the age of 65 years of age will experience a fall. It is important to identify and address modifiable risk factors that are associated with falls in adults at high and low risk for falls.

Hypothesis: Falls risk improves in both high-risk and low-risk participants with the implementation of Stay Active and Independent for Life (SAIL).

Study Design: Cohort study.

Level of Evidence: Level 3.

Methods: Seventy-eight older adults (age, 70.9 ± 5.1 years) were included in this study and categorized into high risk and low risk for falling based on the …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Rab1a Haploinsufficiency Phenocopies The 2p14-P15 Microdeletion And Is Associated With Impaired Neuronal Differentiation, Jonathan J Rios, Yang Li, Nandina Paria, Ryan J Bohlender, Chad Huff, Jill A Rosenfeld, Pengfei Liu, Weimin Bi, Kentaro Haga, Mitsunori Fukuda, Shayal Vashisth, Kiran Kaur, Maria H Chahrour, Michael B Bober, Angela L Duker, Farah A Ladha, Neil A Hanchard, Kristhen Atala, Anas M Khanshour, Linsley Smith, Carol A Wise, Mauricio R Delgado

Faculty, Staff and Student Publications

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and …

Stereotactic Body Radiotherapy With Or Without Selective Dismutase Mimetic In Pancreatic Adenocarcinoma: An Adaptive, Randomised, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial, Cullen M Taniguchi, Jessica M Frakes, Todd A Aguilera, Manisha Palta, Brian Czito, Manoop S Bhutani, Lauren E Colbert, Joseph Abi Jaoude, Vincent Bernard, Shubham Pant, Ching-Wei D Tzeng, Dae Won Kim, Mokenge Malafa, James Costello, Geena Mathew, Neal Rebueno, Eugene J Koay, Prajnan Das, Ethan B Ludmir, Matthew H G Katz, Robert A Wolff, Sam Beddar, Gabriel O Sawakuchi, Shalini Moningi, Rebecca S Slack Tidwell, Ying Yuan, Peter F Thall, Robert A Beardsley, Jon Holmlund, Joseph M Herman, Sarah E Hoffe

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma.

METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six …

Influence Of Treatment Intensity And Medical Comorbidities In Older Adults With Peripheral T Cell Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V Danilov, Swaminathan Iyer, Sharon H Giordano

Faculty, Staff and Student Publications

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N …

Outcome Of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia In The United States Since The Introduction Of Imatinib Therapy–The Surveillance, Epidemiology, And End Results Database, 2000–2019, Koji Sasaki, Fadi G Haddad, Nicholas J Short, Nitin Jain, Ghayas Issa, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: Since the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs) in 2000, the treatment of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) has improved significantly.

Methods: This study aimed to evaluate Ph-positive CML outcomes in the TKI therapy era, considering factors like age, ethnicity, and income. Using the Surveillance, Epidemiology, and End Results (SEER) database, 2857 patients with Ph-positive CML diagnosed from 2000 to 2019 were analyzed.

Results: The overall 5-year survival rates in Ph-positive CML increased to above 80%, compared with pre-TKIs historical data reporting 5-year overall survival (OS) rates of less than 50%. The 5-year OS rate was …

Skin Cancers In Medicare Beneficiaries With Actinic Keratoses, Cassandra Mohr, Yao Li, Lucy J Navsaria, Candice L Hinkston, Sanjay S Shete, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Importance: Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown.

Objective: To calculate the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs.

Design, setting, and participants: This retrospective cohort study was performed using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries from 2009 through 2018. Patients with treated AKs were …

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery Of 187 Novel Risk Variants, Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, David E Neal, Jenny L Donovan, Freddie C Hamdy, Richard M Martin, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A Clements, Wayne Tilly, Gail P Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M Dunning, Maya Ghoussaini, Ruth C Travis, Tim J Key, Elio Riboli, Jong Y Park, Thomas A Sellers, Hui-Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B Cook, Lorelei A Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J Hunter, Kathryn L Penney, Constance Turman, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, Robert J Hamilton, Neil E Fleshner, Antonio Finelli, Marie-Élise Parent, Janet L Stanford, Elaine A Ostrander, Stella Koutros, Laura E Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L Andriole, Robert N Hoover, Mitchell J Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J Blot, Wei Zheng, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-Chao Zhao, Zan Sun, Stephen N Thibodeau, Shannon K Mcdonnell, Daniel J Schaid, Catharine M L West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M John, Eli Marie Grindedal, Lovise Maehle, Kay-Tee Khaw, Sue A Ingles, Mariana C Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S Rosenstein, Sarah L Kerns, Harry Ostrer, Manuel R Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T Bensen, Ebonee N Butler, James L Mohler, Jack A Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C Teerlink, Chad D Huff, Patrick Pilie, Yao Yu, Ryan J Bohlender, Jian Gu, Sara S Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A Klein, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Jeri Kim, Susan L Neuhausen, Linda Steele, Yuan Chun Ding, William B Isaacs, Barbara Nemesure, Anselm J M Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Lisa F Newcomb, Daniel W Lin, Jay H Fowke, Christine M Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A Townsend, Claire Aukim-Hastie, William S Bush, Melinda C Aldrich, Dana C Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P Chokkalingam, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M Gundell, Monique J Roobol, Guido Jenster, Ron H N Van Schaik, Jennifer J Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean-Cowdin, Mina Torres, Michael H Preuss, Ruth J F Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K Van Den Eeden, Douglas F Easton, Stefan Ambs, Todd L Edwards, Reedik Mägi, Timothy R Rebbeck, Lars Fritsche, Stephen J Chanock, Sonja I Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S Witte, J Michael Gaziano, Amy C Justice, Nick Mancuso, Chikashi Terao, Rosalind A Eeles, Zsofia Kote-Jarai, Ravi K Madduri, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in …

Outcomes Of Autologous Stem Cell Transplantation In Patients With Ultra-High-Risk Multiple Myeloma, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Adeel Masood, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM). This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT). We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by …

Repeated Encounters For Actinic Keratoses In Medicare Patients: A Retrospective Cohort Study, Nasim Khalfe, Lucy J Navsaria, Yao Li, Malgorzata K Nowakowska, Carly F Stender, Candice L Hinkston, Sharon H Giordano, Sanjay S Shete, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy In Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial, Yongwoo David Seo, Hailing Lu, Graeme Black, Kimberly Smythe, Yuexin Yu, Cynthia Hsu, Juliana Ng, Pedro Hermida De Viveiros, E Houston Warren, Brett A Schroeder, Ryan B O'Malley, Lee D Cranmer, Elizabeth T Loggers, Michael J Wagner, Lynn Bonham, Venu G Pillarisetty, Gabrielle Kane, Peter Berglund, Frank J Hsu, Xinlei Mi, Borislav A Alexiev, Robert H Pierce, Stanley R Riddell, Robin L Jones, Jan Ter Meulen, Edward Y Kim, Seth M Pollack

Faculty, Staff and Student Publications

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts.

Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions.

Design, setting, and participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis …

Case Of New-Onset Scleromyxoedema-Scleroedema Spectrum Disorder In A Patient With Cll, Yuanteng Jeff Li, Victor G Prieto, Jean Tayar

Faculty, Staff and Student Publications

No abstract provided.

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

A Longitudinal Study Of Polygenic Score And Cognitive Function Decline Considering Baseline Cognitive Function, Lifestyle Behaviors, And Diabetes Among Middle-Aged And Older Us Adults, Tingting Liu, Changwei Li, Ruiyuan Zhang, Eugenia Flores Millender, Hongyu Miao, Michael Ormsbee, Jinzhen Guo, Adrianna Westbrook, Yang Pan, Jing Wang, Tanika N Kelly

Faculty, Staff and Student Publications

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment.

Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 …

Venetoclax Abrogates The Prognostic Impact Of Splicing Factor Gene Mutations In Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Samuel Urrutia, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Abhishek Maiti, Hussein A Abbas, Naval G Daver, Naveen Pemmaraju, Sherry Pierce, Kelly S Chien, Koji Sasaki, Tapan M Kadia, Danielle E Hammond, Gautam Borthakur, Keyur Patel, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Courtney D Dinardo

Faculty, Staff and Student Publications

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Gail Davies, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Faculty, Staff and Student Publications

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Characteristics And Clinical Outcomes Of Patients With Myeloid Malignancies And Ddx41 Variants, Alex Bataller, Sanam Loghavi, Yoheved Gerstein, Alexandre Bazinet, Koji Sasaki, Kelly S Chien, Danielle Hammond, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas Short, Ghayas C Issa, Tapan M Kadia, Naval Daver, Guilin Tang, Andres Quesada, Keyur P Patel, Farhad Ravandi, Warren Fiskus, Cristopher P Mill, Hagop M Kantarjian, Kapil Bhalla, Guillermo Garcia-Manero, Betul Oran, Courtney D Dinardo

Faculty, Staff and Student Publications

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides …

Remotely Delivered Cancer Genetic Testing In The Making Genetic Testing Accessible (Magenta) Trial: A Randomized Clinical Trial, Elizabeth M Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Barbara M Norquist, Tara Coffin, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie N Bakkum-Gamez, Stephanie V Blank, Mark F Munsell, Denise Nebgen, Gini F Fleming, Olufunmilayo I Olopade, Sherman Law, Alicia Zhou, Douglas A Levine, Alan D'Andrea, Karen H Lu

Faculty, Staff and Student Publications

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, setting, and participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US …

Primary Tumor Site For Localized Merkel Cell Carcinoma Drives Different Management Strategies Without Impacting Oncologic Outcomes, Samuel Cass, Brandon Cope, Andrew J Bishop, Yi-Ju Chiang, B Ashleigh Guadagnolo, Ahsan Farooqi, William Morrison, Russell G Witt, Riyad N H Seervai, Adam S Garden, Clifton D Fuller, Ryan P Goepfert, Merrick Ross, Jeffrey E Gershenwald, Michael Wong, Phyu P Aung, Emily Z Keung, Devarati Mitra

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Clinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era.

MATERIALS AND METHODS: Patterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014-2021.

RESULTS: Of 80 patients who met inclusion criteria, the primary tumor anatomic site was head …