Genetic Phenomena Commons^™

Impact Of Revised International Staging System 2 Risk Stratification On Outcomes Of Patients With Multiple Myeloma Receiving Autologous Haematopoietic Stem Cell Transplantation, Kamal Alzahrani, Oren Pasvolsky, Zhongya Wang, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Elisabet E Manasanch, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The second revision of the International Staging System (R2-ISS) is a simple tool to risk-stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective analysis to evaluate the utility of R2-ISS in NDMM patients who underwent up-front autologous haematopoietic stem cell transplantation (auto-HCT). A total of 1291 patients were included, with a median age of 62 years (range 29-83). The distribution of R2-ISS stages was: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III and 131 (10%) stage IV. With a median follow-up of 42.2 months (range 0.3-181.0), the median PFS was 73.0, 65.2, 44.0 …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

A Randomized Trial Of Two Remote Health Care Delivery Models On The Uptake Of Genetic Testing And Impact On Patient-Reported Psychological Outcomes In Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, And Testing (Generate) Study, Nicolette J Rodriguez, C Sloane Furniss, Matthew B Yurgelun, Chinedu Ukaegbu, Pamela E Constantinou, Ileana Fortes, Alyson Caruso, Alison N Schwartz, Jill E Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H Nelson, Sydney Okumura, Alicia Y Zhou, Tara B Coffin, Hajime Uno, Miki Horiguchi, Allyson J Ocean, Florencia Mcallister, Andrew M Lowy, Alison P Klein, Lisa Madlensky, Gloria M Petersen, Judy E Garber, Scott M Lippman, Michael G Goggins, Anirban Maitra, Sapna Syngal

Faculty, Staff and Student Publications

Background & aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session …

Somatic Gene Mutation Patterns And Burden Influence Outcomes With Enasidenib In Relapsed/Refractory Idh2-Mutated Aml, Alberto Risueño, Wendy L See, Iryna Bluemmert, Stéphane De Botton, Courtney D Dinardo, Amir T Fathi, Andre C Schuh, Pau Montesinos, Paresh Vyas, Thomas Prebet, Anita Gandhi, Maroof Hasan

Faculty, Staff and Student Publications

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this …

Azacitidine, Venetoclax, And Gilteritinib In Newly Diagnosed And Relapsed Or Refractory Flt3-Mutated Aml, Nicholas J Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Lewis F Nasr, Walid Macaron, Musa Yilmaz, Gautam Borthakur, Guillermo Montalban-Bravo, Guillermo Garcia-Manero, Ghayas C Issa, Kelly S Chien, Elias Jabbour, Cedric Nasnas, Xuelin Huang, Wei Qiao, Jairo Matthews, Christopher J Stojanik, Keyur P Patel, Regina Abramova, Jennifer Thankachan, Marina Konopleva, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Purpose: Azacitidine plus venetoclax is a standard of care for patients with newly diagnosed AML who are unfit for intensive chemotherapy. However, FLT3 mutations are a common mechanism of resistance to this regimen. The addition of gilteritinib, an oral FLT3 inhibitor, to azacitidine and venetoclax may improve outcomes in patients with FLT3-mutated AML.

Methods: This phase I/II study evaluated azacitidine, venetoclax, and gilteritinib in two cohorts: patients with (1) newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy or (2) relapsed/refractory FLT3-mutated AML (ClinicalTrials.gov identifier: NCT04140487). The primary end points were the maximum tolerated dose …

Survival Disparities In Non-Hispanic Black And White Cervical Cancer Patients Vary By Histology And Are Largely Explained By Modifiable Factors, Calen W Kucera, Nicole P Chappell, Chunqiao Tian, Michael T Richardson, Christopher M Tarney, Chad A Hamilton, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christine Rojas, Collin A Sitler, Lari Wenzel, Ann Klopp, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Timothy D O'Connor, Craig D Shriver, Nicholas W Bateman, Thomas P Conrads, Neil T Phippen, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma …

Automated, High-Throughput Platform To Generate A High-Reliability, Comprehensive Rectal Cancer Database, Neal Bhutiani, Mahmoud M G Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Mark Knafl, Olivia Ratliff, Uditha P Fernando, Anastasia Turin, Fadl A Zeineddine, Jeff Jin, Kristin Alfaro-Munoz, Drew Goldstein, George J Chang, Scott Kopetz, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.

Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and …

Genomic Landscape Of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens For Immunoprevention, Ana M Bolivar, Fahriye Duzagac, Nan Deng, Laura Reyes-Uribe, Kyle Chang, Wenhui Wu, Charles M Bowen, Melissa W Taggart, Selvi Thirumurthi, Patrick M Lynch, Y Nancy You, Jesus Rodriguez-Pascual, Steven M Lipkin, Scott Kopetz, Paul Scheet, Gregory A Lizee, Alexandre Reuben, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Background & aims: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers.

Methods: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 …

Genome-Wide Association Analyses Of Breast Cancer In Women Of African Ancestry Identify New Susceptibility Loci And Improve Risk Prediction, Guochong Jia, Jie Ping, Xingyi Guo, Yaohua Yang, Ran Tao, Bingshan Li, Stefan Ambs, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Dezheng Huo, Esther M John, Christopher I Li, James L Li, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Xiao-Ou Shu, Melissa A Troester, Song Yao, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Huijun Qian, Haoyu Zhang, Christine B Ambrosone, Qiuyin Cai, Jirong Long, Julie R Palmer, Christopher A Haiman, Wei Zheng

Faculty, Staff and Student Publications

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Safety And Tolerability Of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy, Jasmijn M Westerhoff, Lois A Daamen, John P Christodouleas, Erwin L A Blezer, Ananya Choudhury, Rosalyne L Westley, Beth A Erickson, Clifton D Fuller, Shaista Hafeez, Uulke A Van Der Heide, Martijn P W Intven, Anna M Kirby, Susan Lalondrelle, Bruce D Minsky, Stella Mook, Marlies E Nowee, Corrie A M Marijnen, Kristina M Orrling, Arjun Sahgal, Christopher J Schultz, Corinne Faivre-Finn, Robbert J H A Tersteeg, Alison C Tree, Chia-Lin Tseng, Tine Schytte, Dustin M Silk, Dave Eggert, Marco Luzzara, Jochem R N Van Der Voort Van Zyp, Helena M Verkooijen, William A Hall

Faculty, Staff and Student Publications

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy.

Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach).

Design, setting, and participants: This cohort study included adults with solid tumors treated with a …

Artificial Intelligence-Powered Assessment Of Pathologic Response To Neoadjuvant Atezolizumab In Patients With Nsclc: Results From The Lcmc3 Study, Sanja Dacic, William D Travis, Jennifer M Giltnane, Filip Kos, John Abel, Stephanie Hilz, Junya Fujimoto, Lynette Sholl, Jon Ritter, Farah Khalil, Yi Liu, Amaro Taylor-Weiner, Murray Resnick, Hui Yu, Fred R Hirsch, Paul A Bunn, David P Carbone, Valerie Rusch, David J Kwiatkowski, Bruce E Johnson, Jay M Lee, Stephanie R Hennek, Ilan Wapinski, Alan Nicholas, Ann Johnson, Katja Schulze, Mark G Kris, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate.

Methods: We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = …

Financial Hardship And Neighborhood Socioeconomic Disadvantage In Long-Term Childhood Cancer Survivors, Alex J Fauer, Weiyu Qiu, I-Chan Huang, Patricia A Ganz, Jacqueline N Casillas, K Robin Yabroff, Gregory T Armstrong, Wendy Leisenring, Rebecca Howell, Carrie R Howell, Anne C Kirchhoff, Yutaka Yasui, Paul C Nathan

Faculty, Staff and Student Publications

Background: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships.

Methods: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear …

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 …

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), …

Reduced Dose Azacitidine Plus Venetoclax As Maintenance Therapy In Acute Myeloid Leukaemia Following Intensive Or Low-Intensity Induction: A Single-Centre, Single-Arm, Phase 2 Trial, Alexandre Bazinet, Hagop Kantarjian, Alex Bataller, Naveen Pemmaraju, Gautam Borthakur, Kelly Chien, Yesid Alvarado, Prithviraj Bose, Elias Jabbour, Musa Yilmaz, Courtney Dinardo, Ghayas Issa, Guillermo Montalban-Bravo, Nicholas Short, Koji Sasaki, Debra Bull-Linderman, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.

Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible …

Cochlear Implantation After Head And Neck Radiation: A Case Series, Systematic Review, And Meta-Analysis, Jumah G Ahmad, Benjamin D Lovin, Anna Lee, Marc-Elie Nader, Paul W Gidley

Faculty, Staff and Student Publications

Objective: To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in this population through a retrospective cohort review, systematic review, and meta-analysis.

Databases reviewed: PubMed, Cochrane Library, and Embase.

Methods: We retrospectively reviewed all CI cases after head and neck (HN) XRT at our institution, noting intraoperative findings, postoperative complications, and hearing outcomes. Change in speech discrimination scores (SDSs) was the primary outcome measure. Systematic review was performed to identify all cases of CI after HNXRT. A meta-analysis was performed to assess SDS change.

Results: The …

Definitive Single Fraction Spine Stereotactic Radiosurgery For Metastatic Sarcoma: Simultaneous Integrated Boost Is Associated With High Tumor Control And Low Vertebral Fracture Risk, Mihir D Shanker, Adriana P Cavazos, Jing Li, Thomas H Beckham, Debra N Yeboa, Chenyang Wang, Mary Frances Mcaleer, Tina Marie Briere, Behrang Amini, Claudio E Tatsui, Robert Y North, Christopher A Alvarez-Breckenridge, Phillip Cem Cezayirli, Laurence D Rhines, Amol J Ghia, Andrew J Bishop

Faculty, Staff and Student Publications

Introduction: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS).

Materials and methods: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective …

Disease Progression, Survival, And Molecular Disparities In Black And White Patients With Endometrioid Endometrial Carcinoma In Real-World Registries And Gog/Nrg Oncology Randomized Phase Iii Clinical Trials, Zachary A Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T Phippen, Christopher M Tarney, Erica R Hope, Stuart S Winkler, Suzanne Jokajtys, Calen W Kucera, John K Chan, Michael T Richardson, Daniel S Kapp, Chad A Hamilton, Charles A Leath, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Angeles Alvarez Secord, Casey M Cosgrove, Matthew A Powell, Ann Klopp, Joan L Walker, Gini F Fleming, Nicholas W Bateman, Thomas P Conrads, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

A Randomized, Non-Comparative Phase 2 Study Of Neoadjuvant Immune-Checkpoint Blockade In Retroperitoneal Dedifferentiated Liposarcoma And Extremity/Truncal Undifferentiated Pleomorphic Sarcoma, Christina L Roland, Elise F Nassif Haddad, Emily Z Keung, Wei-Lien Wang, Alexander J Lazar, Heather Lin, Manoj Chelvanambi, Edwin R Parra, Khalida Wani, B Ashleigh Guadagnolo, Andrew J Bishop, Elizabeth M Burton, Kelly K Hunt, Keila E Torres, Barry W Feig, Christopher P Scally, Valerae O Lewis, Justin E Bird, Ravin Ratan, Dejka Araujo, M Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P Conley, J Andrew Livingston, Vinod Ravi, Hussein A Tawbi, Patrick P Lin, Bryan S Moon, Robert L Satcher, Bilal Mujtaba, Russell G Witt, Raymond S Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M Mohammad, Randy A Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A Wargo, Neeta Somaiah

Faculty, Staff and Student Publications

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

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 …

Understanding Heterogeneity In Individual Responses To Digital Lifestyle Intervention Through Self-Monitoring Adherence Trajectories In Adults With Overweight Or Obesity: Secondary Analysis Of A 6-Month Randomized Controlled Trial, Shiyu Li, Yan Du, Hongyu Miao, Kumar Sharma, Chengdong Li, Zenong Yin, Bradley Brimhall, Jing Wang

Faculty, Staff and Student Publications

Background: Achieving clinically significant weight loss through lifestyle interventions for obesity management is challenging for most individuals. Improving intervention effectiveness involves early identification of intervention nonresponders and providing them with timely, tailored interventions. Early and frequent self-monitoring (SM) adherence predicts later weight loss success, making it a potential indicator for identifying nonresponders in the initial phase.

Objective: This study aims to identify clinically meaningful participant subgroups based on longitudinal adherence to SM of diet, activity, and weight over 6 months as well as psychological predictors of participant subgroups from a self-determination theory (SDT) perspective.

Methods: This was a secondary data …

Prediabetes And Associated Risk Of Cardiovascular Events And Chronic Kidney Disease Among Adult Survivors Of Childhood Cancer In The St Jude Lifetime Cohort, Stephanie B Dixon, Fang Wang, Lu Lu, Carmen L Wilson, Daniel M Green, Thomas E Merchant, Deo Kumar Srivastava, Angela Delaney, Rebecca M Howell, John L Jefferies, Leslie L Robison, Kirsten K Ness, Melissa M Hudson, Wassim Chemaitilly, Gregory T Armstrong

Faculty, Staff and Student Publications

Purpose: Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors.

Methods: Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) and diabetes was clinically assessed in 3,529 adults ≥5 years from childhood cancer diagnosis and 448 controls stratified by age. Cox proportional hazards regression estimated progression from prediabetes to diabetes, and risk of future cardiac events, stroke, CKD, and death.

Results: Among survivors, median age 30 years (IQR, 18-65), and the prevalence of prediabetes was 29.2% (95% CI, 27.7 to 30.7) …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Surrogate Endpoints In Clinical Trials Of P16-Positive Squamous Cell Carcinoma Of The Oropharynx: An Individual Patient Data Meta-Analysis, Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell, Christopher U Jones, Darrion L Mitchell, Greg Krempl, John A Ridge, Michael F Gensheimer, James A Bonner, Edith Filion, Neal E Dunlap, William A Stokes, Quynh-Thu Le, Pedro Torres-Saavedra, Michelle Mierzwa, Matthew J Schipper

Faculty, Staff and Student Publications

Background: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy.

Methods: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as …

Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Student Publications

Background: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined.

Objectives: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales.

Methods: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020.

Results: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with …

A Study Of Dietary Patterns Derived By Cluster Analysis And Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients, Xiaotao Zhang, Carrie R Daniel, Valeria Soltero, Ximena Vargas, Shilpa Jain, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Student Publications

Introduction: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity.

Methods: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. …