Genetic Phenomena Commons^™

Targeted Accurate Rna Consensus Sequencing (Tarc-Seq) Reveals Mechanisms Of Replication Error Affecting Sars-Cov-2 Divergence, Catherine C Bradley, Chen Wang, Alasdair J E Gordon, Alice X Wen, Pamela N Luna, Matthew B Cooke, Brendan F Kohrn, Scott R Kennedy, Vasanthi Avadhanula, Pedro A Piedra, Olivier Lichtarge, Chad A Shaw, Shannon E Ronca, Christophe Herman

Duncan NRI Faculty and Staff Publications

RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error-prone. Monitoring replication errors is crucial for understanding the virus’s evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here, we introduce a new targeted Accurate RNA Consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples. Our findings show an average of 2.68×10−5 new errors per cycle with a C>T bias that cannot be solely attributed to APOBEC …

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 …

Supporting Career Development For Early- And Mid-Career Professionals Working In The Bipolar Disorder Field: Key Initiatives To Be Implemented By The International Society For Bipolar Disorders Early- And Mid-Career Committee, Katie M Douglas, Sarah H Sperry, Olivia M Dean, Gabriel R Fries, Fabiano A Gomes, Joanna Jiménez Pavón, Emma Morton, Rachel H B Mitchell, Tamsyn E Van Rheenen, Norma Verdolini, Ni Xu, Georgina M Hosang, Rebekah S Huber

Faculty, Staff and Student Publications

No abstract provided.

Management And Outcomes Of Patients With Refractory Solitary Plasmacytoma After Treatment With Definitive Radiation Therapy, Penny Fang, Chelsea C Pinnix, Susan Y Wu, Hans C Lee, Krina K Patel, Neeraj Saini, Melody R Becnel, Gregory Kaufman, Sheeba K Thomas, Robert Z Orlowski, Behrang Amini, Pei Lin, Bouthaina S Dabaja, Jillian R Gunther

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes.

Methods and materials: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes.

Results: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT …

Intermittent Fasting And Its Impact On Toxicities, Symptoms And Quality Of Life In Patients On Active Cancer Treatment, Robert Li Sucholeiki, Casey L Propst, David S Hong, Goldy C George

Faculty, Staff and Student Publications

Intermittent fasting is a dietary intervention that is increasingly being tested for positive outcomes in patients receiving cancer treatment. In this review, we examine the impact of intermittent fasting on symptoms, toxicities, and quality of life in patients undergoing cancer therapy and highlight unmet investigative areas to prompt future research. While current evidence is preliminary and conclusions mixed, some promising clinical studies suggest that intermittent fasting interventions may improve fatigue and reduce gastrointestinal toxicities in certain patients with cancer. Emerging clinical evidence also demonstrates that intermittent fasting may reduce off-target DNA damage, and induce favorable cellular-level immune remodeling. Furthermore, intermittent …

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 …

Assessing The Impact Of The Covid-19 Pandemic On Training At The Md Anderson Cancer Center Anatomical Pathology Fellowship Program, Yiannis P Dimopoulos, Donghyang Kwon, Denái R Milton, Paula I Iaeger, Donna E Hansel, Victor G Prieto, Kareen E Chin, Phyu P Aung

Faculty, Staff and Student Publications

Context: To provide high-quality, safe training during the COVID-19 pandemic, our anatomic pathology fellowship program implemented a hybrid virtual/in-person training model with supplemental digital material.

Objective: To evaluate the impact of this model.

Design: We examined Accreditation Council for Graduate Medical Education survey results and board pass rates for fellows before the pandemic (group 1); during the pandemic peak (group 2); and early and late after the pandemic peak (groups 3 and 4). Additionally, we distributed an online survey, including questions related to performance as attending physicians and fellowship experience, to recent graduates.

Results: Information loss during handover, supervision and …

Optimized Scoring Of End-To-End Dosimetry Audits For Passive Motion Management – A Simulation Study Using The Iroc Thorax Phantom, Alex Burton, Mathieu Gaudreault, Nicholas Hardcastle, Jessica Lye, Sabeena Beveridge, Stephen F Kry, Rick Franich

Faculty, Staff and Student Publications

Dosimetry audits for passive motion management require dynamically-acquired measurements in a moving phantom to be compared to statically calculated planned doses. This study aimed to characterise the relationship between planning and delivery errors, and the measured dose in the Imaging and Radiation Oncology Core (IROC) thorax phantom, to assess different audit scoring approaches. Treatment plans were created using a 4DCT scan of the IROC phantom, equipped with film and thermoluminescent dosimeters (TLDs). Plans were created on the average intensity projection from all bins. Three levels of aperture complexity were explored: dynamic conformal arcs (DCAT), low-, and high-complexity volumetric modulated arcs …

Updates On Who Classification For Small Round Cell Tumors: Ewing Sarcoma Vs Everything Else, Carina A Dehner, Alexander J Lazar, John S A Chrisinger

Faculty, Staff and Student Publications

The WHO Classification of Soft Tissue and Bone Tumours currently recognizes four categories of undifferentiated small round cell sarcoma: Ewing sarcoma, round cell sarcoma with EWSR1-non-ETS fusions including NFATc2 and PATZ1, CIC-rearranged sarcoma, and sarcoma with BCOR genetic alterations. These neoplasms frequently pose significant diagnostic challenges due to rarity and overlapping morphologic and immunohistochemical findings. Further, molecular testing, with accompanying pitfalls, may be needed to establish a definitive diagnosis. This review summarizes the clinical, histologic, immunohistochemical, and molecular features of these neoplasms. In addition, differential diagnosis and areas of uncertainty and ongoing investigation are discussed.

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 …

Cross-Vendor Multiparametric Mapping Of The Human Brain Using 3d-Qalas: A Multicenter And Multivendor Study, Shohei Fujita, Borjan Gagoski, Ken-Pin Hwang, Akifumi Hagiwara, Marcel Warntjes, Issei Fukunaga, Wataru Uchida, Yuya Saito, Towa Sekine, Rina Tachibana, Tomoya Muroi, Toshiya Akatsu, Akihiro Kasahara, Ryo Sato, Tsuyoshi Ueyama, Christina Andica, Koji Kamagata, Shiori Amemiya, Hidemasa Takao, Yasunobu Hoshino, Yuji Tomizawa, Kazumasa Yokoyama, Berkin Bilgic, Nobutaka Hattori, Osamu Abe, Shigeki Aoki

Faculty, Staff and Student Publications

Purpose: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping.

Methods: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions …

Mapping Genotypes To Chromatin Accessibility Profiles In Single Cells, Franco Izzo, Robert M Myers, Saravanan Ganesan, Levan Mekerishvili, Sanjay Kottapalli, Tamara Prieto, Elliot O Eton, Theo Botella, Andrew J Dunbar, Robert L Bowman, Jesus Sotelo, Catherine Potenski, Eleni P Mimitou, Maximilian Stahl, Sebastian El Ghaity-Beckley, Joann Arandela, Ramya Raviram, Daniel C Choi, Ronald Hoffman, Ronan Chaligné, Omar Abdel-Wahab, Peter Smibert, Irene M Ghobrial, Joseph M Scandura, Bridget Marcellino, Ross L Levine, Dan A Landau

Faculty, Staff and Student Publications

In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates1-3. Therefore, somatic mutations are likely to alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. Here, to chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed genotyping of targeted loci with single-cell chromatin accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution across thousands of cells within a single assay. …

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.

A West African Ancestry-Associated Snp On 8q24 Predicts A Positive Biopsy In African American Men With Suspected Prostate Cancer Following Psa Screening, Jian Gu, Lisly Chery, Graciela M Nogueras González, Chad Huff, Sara Strom, Jeffrey A Jones, Donald P Griffith, Steven E Canfield, Xuemei Wang, Xuelin Huang, Pamela Roberson, Qing H Meng, Patricia Troncoso, Michael Ittmann, Michael Covinsky, Michael Scheurer, Margarita Irizarry Ramirez, Curtis A Pettaway

Faculty, Staff and Student Publications

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, …

Dynamics Of Karyotype Evolution, Elena Kuzmin, Toby M Baker, Peter Van Loo, Leon Glass

Faculty, Staff and Student Publications

In the evolution of species, the karyotype changes with a timescale of tens to hundreds of thousand years. In the development of cancer, the karyotype often is modified in cancerous cells over the lifetime of an individual. Characterizing these changes and understanding the mechanisms leading to them has been of interest in a broad range of disciplines including evolution, cytogenetics, and cancer genetics. A central issue relates to the relative roles of random vs deterministic mechanisms in shaping the changes. Although it is possible that all changes result from random events followed by selection, many results point to other non-random …

Pet Imaging Of Metabolism, Perfusion, And Hypoxia: Fdg And Beyond, Austin R Pantel, Seong-Woo Bae, Elizabeth J Li, Sophia R O'Brien, H Charles Manning

Faculty, Staff and Student Publications

Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Caron A Jacobson, Sairah Ahmed, David B Miklos, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

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 = …

Discovering Genetic Biomarkers For Targeted Cancer Therapeutics With Explainable Artificial Intelligence, Debaditya Chakraborty, Elizabeth Gutierrez-Chakraborty, Cristian Rodriguez-Aguayo, Hakan Başağaoğlu, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

No abstract provided.

Survival Outcomes Of Patients With Her2/Neu-Positive Breast Cancer With Germline Brca Mutations, Fatma Nihan Akkoc Mustafayev, Mihir Amitabh Shukla, Amanda Lanier, Denái R Milton, Angelica M Gutierrez, Stephen K Gruschkus, John E Lewis, Rashmi K Murthy, Banu K Arun

Faculty, Staff and Student Publications

Background: Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations.

Methods: This was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu-positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were …

A Novel Sik2 Inhibitor Sic-19 Exhibits Synthetic Lethality With Parp Inhibitors In Ovarian Cancer, Fang Wang, Xuejiao Yu, Jun Qian, Yumin Cao, Shunli Dong, Shenghua Zhan, Zhen Lu, Robert C Bast, Qingxia Song, Youguo Chen, Yi Zhang, Jinhua Zhou

Faculty, Staff and Student Publications

Purpose: Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer.

Methods: The SIK2 protein was modeled using a Molecular Operating Environment (MOE), and the most favorable model was selected based on a GBVI/WSA dG scoring function. The Chembridge Compound Library was screened, and the top 20 candidate compounds were tested for their interaction with SIK2 and downstream substrates, …

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 …

Culturally Competent Education And Human Papillomavirus Self-Sampling Achieves Healthy People 2030 Cervical Screening Target Among Low-Income Non-Hispanic Black And Hispanic Women, Surendra S Shastri, Lorna H Mcneill, Sanjay Shete

Faculty, Staff and Student Publications

Purpose: Disparities in cervical cancer screening, incidence, and mortality exist in the United States. Cervical cancer incidence and mortality rates in Texas are 20% and 32% higher, respectively, than national averages. Within Texas, these rates are significantly higher among non-Hispanic (NH) Black and Hispanic women. Cervical cancer screening uptake is lower among NH Black and Hispanic women (72.9% and 75.9%, respectively) compared with White women (85.5%) in Texas.

Methods: During March-August 2023, we conducted a pilot study that offered culturally competent education and human papillomavirus (HPV) self-sampling kits to women in two public housing projects in Houston, TX, that have …

Fungi In Cancer, Jessica Galloway-Peña, Iliyan D Iliev, Florencia Mcallister

Faculty, Staff and Student Publications

Both the gut and the tumour microbiome are now established as crucial regulators of cancer phenotypes and have been implicated in cancer initiation, progression and therapy response. Although the role of bacteria in these processes is beginning to be unravelled, the relevance of fungi is only just emerging. In this Viewpoint, we asked experts to discuss the current knowledge on the mycobiome–cancer connection and share their opinion on how to best solve open questions.

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 …

Impact Of Pretransplant Minimal Residual Disease In Patients With Multiple Myeloma And A Very Good Partial Response Or Better Receiving Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Sarah Pasyar, Roland L Bassett, Hina N Khan, 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

Background: The prognostic significance of minimal residual disease (MRD) status before autologous hematopoietic stem cell transplantation (autoHCT) in patients with multiple myeloma (MM) has not been clearly elucidated.

Methods: Retrospective single-center study of adult MM patients who achieved ≥very good partial response (VGPR) after induction therapy from 2015 to 2021 received upfront autoHCT and had available pretransplant MRD status by next-generation flow cytometry. The cohort was divided into pretransplant MRD-negative (MRDneg) and MRD-positive (MRDpos) groups.

Results: A total of 733 patients were included in our analysis; 425 were MRDneg and 308 MRDpos at autoHCT. In the MRDpos group, more patients …