Medical Genetics Commons^™

Chronic Eosinophilic Leukemia With A Novel Jak1 Mutation Responds Well To The Jak1/2 Inhibitor Ruxolitinib, Qing Wei, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Radiation Therapy With Or Without Cisplatin For Local Recurrences Of Endometrial Cancer: Results From An Nrg Oncology/Gog Prospective Randomized Multicenter Clinical Trial, Ann H Klopp, Danielle Enserro, Matthew Powell, Marcus Randall, Julian C Schink, Robert S Mannel, Laura Holman, David Bender, Christina L Kushnir, Floor Backes, Susan L Zweizig, Steven Waggoner, Kristin A Bradley, Lana Desouza Lawrence, Parviz Hanjani, Christopher J Darus, William Small, Higinia R Cardenes, Jonathan M Feddock, David S Miller

Faculty, Staff and Student Publications

Purpose: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy.

Materials and methods: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS.

Results: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to …

The Cns Relapse In T-Cell Lymphoma Index Predicts Cns Relapse In Patients With T- And Nk-Cell Lymphomas, Rahul S Bhansali, Fredrik Ellin, Thomas Relander, Miao Cao, Wenrui Li, Qi Long, Nivetha Ganesan, Robert Stuver, Steven M Horwitz, Kitsada Wudhikarn, Steven R Hwang, N Nora Bennani, Julio Chavez, Lubomir Sokol, Hayder Saeed, Frank Duan, Pierluigi Porcu, Priyanka Pullarkat, Neha Mehta-Shah, Jasmine M Zain, Miguel Ruiz, Jonathan E Brammer, Rishab Prakash, Swaminathan P Iyer, Adam J Olszewski, Ajay Major, Peter A Riedell, Sonali M Smith, Caroline Goldin, Bradley Haverkos, Bei Hu, Tony Z Zhuang, Pamela B Allen, Wael Toama, Murali Janakiram, Taylor R Brooks, Deepa Jagadeesh, Nisha Hariharan, Aaron M Goodman, Gabrielle Hartman, Paola Ghione, Fatima Fayyaz, Joanna M Rhodes, Elise A Chong, James N Gerson, Daniel J Landsburg, Sunita D Nasta, Stephen J Schuster, Jakub Svoboda, Mats Jerkeman, Stefan K Barta

Faculty, Staff and Student Publications

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. …

Hur Controls Glutaminase Rna Metabolism, Douglas Adamoski, Larissa M Dos Reis, Ana Carolina Paschoalini Mafra, Felipe Corrêa-Da-Silva, Pedro Manoel Mendes De Moraes-Vieira, Ioana Berindan-Neagoe, George A Calin, Sandra Martha Gomes Dias

Faculty, Staff and Student Publications

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and …

Genomic Determinants Of Response And Resistance To Inotuzumab Ozogamicin In B-Cell All, Yaqi Zhao, Nicholas J Short, Hagop M Kantarjian, Ti-Cheng Chang, Pankaj S Ghate, Chunxu Qu, Walid Macaron, Nitin Jain, Beenu Thakral, Aaron H Phillips, Joseph Khoury, Guillermo Garcia-Manero, Wenchao Zhang, Yiping Fan, Hui Yang, Rebecca S Garris, Lewis F Nasr, Richard W Kriwacki, Kathryn G Roberts, Marina Konopleva, Elias J Jabbour, Charles G Mullighan

Faculty, Staff and Student Publications

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of the response and resistance to InO. Pre- and post-InO-treated patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO-relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation and destabilization) and epitope alteration. Two CD22 mutant cases were post-InO …

Loss Of The Dna Repair Gene Rnase H2 Identifies A Unique Subset Of Ddr-Deficient Leiomyosarcomas, Michael S Nakazawa, Ian M Silverman, Victoria Rimkunas, Artur Veloso, Dominik Glodzik, Adrienne Johnson, Toshiro K Ohsumi, Shreyaskumar R Patel, Anthony P Conley, Christina L Roland, Pamela T Soliman, Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Rossana Lazcano, Dawon Song, Khalida M Wani, Alexander J Lazar, Timothy A Yap, Wei-Lien Wang, J Andrew Livingston

Faculty, Staff and Student Publications

Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR-targeted treatments. Therefore, we designed a protein- and genomic-based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS; 30%, 39/102). In …

A Risk Is Not A Harm: Abortion Exceptions In State Laws, Trevor M Bibler, Alison Suen

Center for Medical Ethics and Health Policy Staff Publications

This letter responds to the article "Beneath the Sword of Damocles: Moral Obligations of Physicians in a Post-Dobbs Landscape," by Anne Drapkin Lyerly, Ruth R. Faden, and Michelle M. Mello, in the May-June 2024 issue of the Hastings Center Report.

Understanding The Genetic Complexity Of Puberty Timing Across The Allele Frequency Spectrum, Katherine A Kentistou, Lena R Kaisinger, Stasa Stankovic, Marc Vaudel, Edson Mendes De Oliveira, Andrea Messina, Robin G Walters, Xiaoxi Liu, Alexander S Busch, Hannes Helgason, Deborah J Thompson, Federico Santoni, Konstantin M Petricek, Yassine Zouaghi, Isabel Huang-Doran, Daniel F Gudbjartsson, Eirik Bratland, Kuang Lin, Eugene J Gardner, Yajie Zhao, Raina Y Jia, Chikashi Terao, Marjorie J Riggan, Manjeet K Bolla, Mojgan Yazdanpanah, Nahid Yazdanpanah, Jonathan P Bradfield, Linda Broer, Archie Campbell, Daniel I Chasman, Diana L Cousminer, Nora Franceschini, Lude H Franke, Giorgia Girotto, Chunyan He, Marjo-Riitta Järvelin, Peter K Joshi, Yoichiro Kamatani, Robert Karlsson, Jian'an Luan, Kathryn L Lunetta, Reedik Mägi, Massimo Mangino, Sarah E Medland, Christa Meisinger, Raymond Noordam, Teresa Nutile, Maria Pina Concas, Ozren Polašek, Eleonora Porcu, Susan M Ring, Cinzia Sala, Albert V Smith, Toshiko Tanaka, Peter J Van Der Most, Veronique Vitart, Carol A Wang, Gonneke Willemsen, Marek Zygmunt, Thomas U Ahearn, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Paul L Auer, Catriona L K Barnes, Matthias W Beckmann, Amy Berrington De Gonzalez, Natalia V Bogdanova, Stig E Bojesen, Hermann Brenner, Julie E Buring, Federico Canzian, Jenny Chang-Claude, Fergus J Couch, Angela Cox, Laura Crisponi, Kamila Czene, Mary B Daly, Ellen W Demerath, Joe Dennis, Peter Devilee, Immaculata De Vivo, Thilo Dörk, Alison M Dunning, Miriam Dwek, Johan G Eriksson, Peter A Fasching, Lindsay Fernandez-Rhodes, Liana Ferreli, Olivia Fletcher, Manuela Gago-Dominguez, Montserrat García-Closas, José A García-Sáenz, Anna González-Neira, Harald Grallert, Pascal Guénel, Christopher A Haiman, Per Hall, Ute Hamann, Hakon Hakonarson, Roger J Hart, Martha Hickey, Maartje J Hooning, Reiner Hoppe, John L Hopper, Jouke-Jan Hottenga, Frank B Hu, Hanna Huebner, David J Hunter, Helena Jernström, Esther M John, David Karasik, Elza K Khusnutdinova, Vessela N Kristensen, James V Lacey, Diether Lambrechts, Lenore J Launer, Penelope A Lind, Annika Lindblom, Patrik K E Magnusson, Arto Mannermaa, Mark I Mccarthy, Thomas Meitinger, Cristina Menni, Kyriaki Michailidou, Iona Y Millwood, Roger L Milne, Grant W Montgomery, Heli Nevanlinna, Ilja M Nolte, Dale R Nyholt, Nadia Obi, Katie M O'Brien, Kenneth Offit, Albertine J Oldehinkel, Sisse R Ostrowski, Aarno Palotie, Ole B Pedersen, Annette Peters, Giulia Pianigiani, Dijana Plaseska-Karanfilska, Anneli Pouta, Alfred Pozarickij, Paolo Radice, Gad Rennert, Frits R Rosendaal, Daniela Ruggiero, Emmanouil Saloustros, Dale P Sandler, Sabine Schipf, Carsten O Schmidt, Marjanka K Schmidt, Kerrin Small, Beatrice Spedicati, Meir Stampfer, Jennifer Stone, Rulla M Tamimi, Lauren R Teras, Emmi Tikkanen, Constance Turman, Celine M Vachon, Qin Wang, Robert Winqvist, Alicja Wolk, Babette S Zemel, Wei Zheng, Ko W Van Dijk, Behrooz Z Alizadeh, Stefania Bandinelli, Eric Boerwinkle, Dorret I Boomsma, Marina Ciullo, Georgia Chenevix-Trench, Francesco Cucca, Tõnu Esko, Christian Gieger, Struan F A Grant, Vilmundur Gudnason, Caroline Hayward, Ivana Kolčić, Peter Kraft, Deborah A Lawlor, Nicholas G Martin, Ellen A Nøhr, Nancy L Pedersen, Craig E Pennell, Paul M Ridker, Antonietta Robino, Harold Snieder, Ulla Sovio, Tim D Spector, Doris Stöckl, Cathie Sudlow, Nic J Timpson, Daniela Toniolo, André Uitterlinden, Sheila Ulivi, Henry Völzke, Nicholas J Wareham, Elisabeth Widen, James F Wilson, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Paul D P Pharoah, Liming Li, Douglas F Easton, Pål R Njølstad, Patrick Sulem, Joanne M Murabito, Anna Murray, Despoina Manousaki, Anders Juul, Christian Erikstrup, Kari Stefansson, Momoko Horikoshi, Zhengming Chen, I Sadaf Farooqi, Nelly Pitteloud, Stefan Johansson, Felix R Day, John R B Perry, Ken K Ong

Faculty, Staff and Student Publications

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, …

Evaluating Automatically Generated Normal Tissue Contours For Safe Use In Head And Neck And Cervical Cancer Treatment Planning, Raphael Douglas, Adenike Olanrewaju, Raymond Mumme, Lifei Zhang, Beth M Beadle, Laurence Edward Court

Faculty, Staff and Student Publications

Purpose: Volumetric-modulated arc therapy (VMAT) is a widely accepted treatment method for head and neck (HN) and cervical cancers; however, creating contours and plan optimization for VMAT plans is a time-consuming process. Our group has created an automated treatment planning tool, the Radiation Planning Assistant (RPA), that uses deep learning models to generate organs at risk (OARs), planning structures and automates plan optimization. This study quantitatively evaluates the quality of contours generated by the RPA tool.

Methods: For patients with HN (54) and cervical (39) cancers, we retrospectively generated autoplans using the RPA. Autoplans were generated using deep-learning and RapidPlan …

Cancer Incidence After Diagnosis Of Abdominal Aortic Aneurysm-Brief Report, Lingfeng Luo, Allen M Haas, Caitlin F Bell, Richard A Baylis, Shaunak S Adkar, Changhao Fu, Ivan Angelov, Sharon H Giordano, Derek Klarin, Nicholas J Leeper, Kevin T Nead

Faculty, Staff and Student Publications

Background: Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic pathogenesis from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors.

Methods: All individuals ≥18 years of age with ≥36 months of …

Breast Cancer (Bc) And Severe Covid-19 (C-19) Outcomes: A Matched Analysis, Marija Sullivan, Xiudong Lei, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Patients with cancer receiving anticancer treatment have a higher risk of severe COVID-19 (C-19) outcomes. We examine the association between breast cancer (BC), recent treatment (systemic therapy, surgery, radiation), and C-19 outcomes.

Methods: Retrospective matched cohort study using the Optum® de-identified C-19 Electronic Health Record dataset (2007-2022). Patients with C-19 were categorized into: no cancer, BC with recent treatment, and BC without recent treatment and matched based on age, C-19 diagnosis date, and comorbidity score. We evaluated 30-day mortality, mechanical ventilation, intensive care unit (ICU) stay, and hospitalization. A composite outcome including all outcomes was analyzed. Multivariable logistic regression …

Sequencing Of Kaposi’S Sarcoma Herpesvirus (Kshv) Genomes From Persons Of Diverse Ethnicities And Provenances With Kshv-Associated Diseases Demonstrate Multiple Infections, Novel Polymorphisms, And Low Intra-Host Variance, Vickie A Marshall, Elena M Cornejo Castro, Charles A Goodman, Nazzarena Labo, Isabella Liu, Nicholas C Fisher, Kyle N Moore, Ananthakrishnan Nair, Taina Immonen, Brandon F Keele, Mark N Polizzotto, Thomas S Uldrick, Yunxiang Mu, Tanuja Saswat, Laurie T Krug, Kevin M Mcbride, Kathryn Lurain, Ramya Ramaswami, Robert Yarchoan, Denise Whitby

Faculty, Staff and Student Publications

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. …

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality: A Prospective Cohort Study Within The Uk Biobank, Fangyu Li, Yukiko Yano, Lola Étiévant, Carrie R Daniel, Shreela V Sharma, Eric L Brown, Ruosha Li, Erikka Loftfield, Qing Lan, Rashmi Sinha, Baharak Moshiree, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank.

Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 …

High-Dimensional Multivariate Analysis Of Variance Via Geometric Median And Bootstrapping, Guanghui Cheng, Ruitao Lin, Liuhua Peng

Faculty, Staff and Student Publications

The geometric median, which is applicable to high-dimensional data, can be viewed as a generalization of the univariate median used in 1-dimensional data. It can be used as a robust estimator for identifying the location of multi-dimensional data and has a wide range of applications in real-world scenarios. This paper explores the problem of high-dimensional multivariate analysis of variance (MANOVA) using the geometric median. A maximum-type statistic that relies on the differences between the geometric medians among various groups is introduced. The distribution of the new test statistic is derived under the null hypothesis using Gaussian approximations, and its consistency …

Exploring The Landscape Of Somatic Asxl2 Mutations In Myeloid Neoplasms: Frequency And Clinical Implications, Tareq Abuasab, Gautam Borthakur, Rashmi Kanagal-Shamanna, Lucia Masarova, Keyur Patel, Koichi Takahashi, Prithviraj Bose, John Villarreal, Sherry Pierce, Tapan Kadia, Guillermo Garcia-Manero, Nicholas J Short, Courtney Dinardo, Naval Daver, Farhad Ravandi, Hagop Kantarjian, Srdan Verstovsek, Musa Yilmaz

Faculty, Staff and Student Publications

No abstract provided.

Health-Related Quality Of Life In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, Bortezomib, And Dexamethasone: Patient-Reported Outcomes From Griffin, Rebecca Silbermann, Jacob Laubach, Jonathan L Kaufman, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Katharine S Gries, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

In the phase 2 GRIFFIN trial (ClinicalTrials.gov identifier: NCT02874742), daratumumab added to lenalidomide, bortezomib, and dexamethasone (D-RVd) improved depth of response and progression-free survival (PFS) versus lenalidomide, bortezomib, and dexamethasone (RVd) alone in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) collected using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30-item (QLQ-C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module 20-item (QLQ-MY20), and EuroQol 5-Dimension 5-Level (EQ-5D-5L) tools on day 1 of cycles 1, 2, and 3; on day 21 of cycle 4 (end of …

Impact Of Apolipoprotein E Genotype On Neurocognitive Function In Patients With Brain Metastases: An Analysis Of Nrg Oncology's Rtog 0614, Jeffrey S Wefel, Snehal Deshmukh, Paul D Brown, David R Grosshans, Erik P Sulman, Jane H Cerhan, Minesh P Mehta, Deepak Khuntia, Wenyin Shi, Mark V Mishra, John H Suh, Nadia N Laack, Yuhchyau Chen, Amarinthia Amy Curtis, Joanna M Laba, Ahmed Elsayed, Anu Thakrar, Stephanie L Pugh, Deborah W Bruner

Faculty, Staff and Student Publications

Purpose: Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT.

Methods and materials: NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/- memantine), performed …

Mitochondrial Health, Physical Functioning, And Daily Affect: Bioenergetic Mechanisms Of Dementia Caregiver Well-Being, E Lydia Wu-Chung, Luis D Medina, Jensine Paoletti-Hatcher, Vincent Lai, Jennifer M Stinson, Itee Mahant, Paul E Schulz, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Objective: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health.

Methods: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. …

Genetic Analysis Of Seven Patients With Inherited Ichthyosis And Nagashima-Type Palmoplantar Keratoderma, Jing Zhang, Yue Yao, Ya Tan, Hua-Ying Hu, Lin-Xi Zeng, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole-exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis-like but distinct clinical manifestations. …

Response-Adapted Ultra-Low-Dose 4 Gy Radiation As Definitive Therapy Of Gastric Malt Lymphoma: A Single-Centre, Pilot Trial, Jillian R Gunther, Jie Xu, Manoop S Bhutani, Paolo Strati, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Wenli Dong, Priya R Bhosale, Christopher R Flowers, Ranjit Nair, Luis Malpica Castillo, Luis Fayad, Swaminathan P Iyer, Simrit Parmer, Michael Wang, Hun Ju Lee, Felipe Samaniego, Jason Westin, Sairah Ahmed, Chijioke C Nze, Preetesh Jain, Sattva S Neelapu, Maria A Rodriguez, Dai Chihara, Loretta J Nastoupil, Chelsea C Pinnix

Faculty, Staff and Student Publications

Background: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach.

Methods: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total …

Lacrimal Gland Adenocarcinoma Clinicopathologic Features And Outcomes Compared With Those Of Lacrimal Gland Adenoid Cystic Carcinoma, Hila Goldberg, Xinyang Jiang, Janet Fan, Jiawei Zhao, Jing Ning, Michelle Williams, Steven Frank, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC).

Methods: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed.

Results: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All …

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Sam Yuen, Tycel J Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R Flowers

Faculty, Staff and Student Publications

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months …

Delivery Of Hereditary Cancer Genetics Services To Patients Newly Diagnosed With Ovarian And Endometrial Cancers At Three Gynecologic Oncology Clinics In The Usa, Brazil, And Mexico, Erica M Bednar, Keiry A Paiz, Karen H Lu, Aline Patricia Soares Dias De Souza, Gabriela Oliveira, Carlos E Eduardo Mattos Da Cunha Andrade, Lenny Gallardo, Jairo Rubio-Cordero, David Cantu-De-León, Jose Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic.

Methods: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer …

Mycophenolate Mofetil Is Associated With Inferior Overall Survival In Cytomegalovirus-Seropositive Patients With Acute Myeloid Leukemia Undergoing Hematopoietic Cell Transplantation, Rima M Saliba, Stephanie J Lee, Paul A Carpenter, Geoffrey R Hill, Catherine J Lee, Amin Alousi, May Daher, George Chen, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall, Rohtesh S Mehta

Faculty, Staff and Student Publications

No abstract provided.

Apoptosis Pathway-Associated Proteins Are Frequently Expressed In Melanoma: A Study Of 32 Cases With Focus On Acral Lentiginous Melanoma, Debora A Ledesma, Mario L Marques-Piubelli, Elsa Li-Ning-Tapia, Courtney Hudgens, Jun Gu, Rossana Lazcano, Sandro Casavilca-Zambrano, Miluska Castillo, Michael A Davies, Wen-Jen Hwu, Phyu P Aung, Alessio Giubellino, Jonathan L Curry, Carlos Torres-Cabala

Faculty, Staff and Student Publications

Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and …

Developing A Fit-For-Purpose Composite Symptom Score As A Symptom Burden Endpoint For Clinical Trials In Patients With Malignant Pleural Mesothelioma, Charles S Cleeland, Karen N Keating, Brian Cuffel, Cem Elbi, Jonathan M Siegel, Christoph Gerlinger, Tara Symonds, Jeff A Sloan, Amylou C Dueck, Andrew Bottomley, Xin Shelley Wang, Loretta A Williams, Tito R Mendoza

Faculty, Staff and Student Publications

We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Variance-Components Tests For Genetic Association With Multiple Interval-Censored Outcomes, Jaihee Choi, Zhichao Xu, Ryan Sun

Faculty, Staff and Student Publications

Massive genetic compendiums such as the UK Biobank have become an invaluable resource for identifying genetic variants that are associated with complex diseases. Due to the difficulties of massive data collection, a common practice of these compendiums is to collect interval-censored data. One challenge in analyzing such data is the lack of methodology available for genetic association studies with interval-censored data. Genetic effects are difficult to detect because of their rare and weak nature, and often the time-to-event outcomes are transformed to binary phenotypes for access to more powerful signal detection approaches. However transforming the data to binary outcomes can …

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Immunotherapy In Locally Advanced Cervical Cancer: Integrating Keynote-A18 Into Management Strategies, Jeffrey A How, Amir A Jazaeri

Faculty, Staff and Student Publications

In locally advanced cervical cancer (LACC), the benefit of PD-1 blockade was unknown. In KEYNOTE-A18, Lorusso et al.1 compared the efficacy and safety of adding pembrolizumab to chemoradiation in LACC and demonstrated favorable outcomes. Given multiple approved indications of pembrolizumab in cervical cancer, strategies for optimal integration into management will be needed to maximize overall survival.