Digital Commons Network^™

Outcomes Of Patients Treated With Chemotherapy For Breast Cancer During Pregnancy Compared With Nonpregnant Breast Cancer Patients Treated With Systemic Therapy, Helen M Johnson, Juhee Song, Carla L Warneke, Ashley L Martinez, Jennifer K Litton, Oluchi C Oke

Faculty, Staff and Student Publications

Introduction: Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype.

Methods: PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible. Disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression.

Results: Among 143 PrBC and 285 nonpregnant patients, median follow-up was 11.4 years. …

A Pan-Tumor Review Of The Role Of Poly(Adenosine Diphosphate Ribose) Polymerase Inhibitors, Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh, Zeynep Irem Ozay, Arshit Narang, Tony Crispino, Talia Golan, Jennifer K Litton, Umang Swami, Kathleen N Moore, Neeraj Agarwal

Faculty, Staff and Student Publications

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical …

Outcomes With Bridging Radiation Therapy Prior To Chimeric Antigen Receptor T-Cell Therapy In Patients With Aggressive Large B-Cell Lymphomas, Gohar S Manzar, Chelsea C Pinnix, Stephanie O Dudzinski, Kathryn E Marqueen, Elaine E Cha, Lewis F Nasr, Alison K Yoder, Michael K Rooney, Paolo Strati, Sairah Ahmed, Chijioke Nze, Ranjit Nair, Luis E Fayad, Michael Wang, Loretta J Nastoupil, Jason R Westin, Christopher R Flowers, Sattva S Neelapu, Jillian R Gunther, Bouthaina S Dabaja, Susan Y Wu, Penny Q Fang

Faculty, Staff and Student Publications

Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.

Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney …

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Patterns Of Loco-Regional Progression And Patient Outcomes After Definitive-Dose Radiation Therapy For Anaplastic Thyroid Cancer, Julianna K Bronk, Alexander Augustyn, Abdallah S R Mohamed, C David Fuller, Adam S Garden, Amy C Moreno, Anna Lee, William H Morrison, Jack Phan, Jay P Reddy, David I Rosenthal, Michael T Spiotto, Steven J Frank, Ramona Dadu, Naifa Busaidy, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Renata Ferrarotto, Priyanka C Iyer, Maria E Cabanillas, G Brandon Gunn

Faculty, Staff and Student Publications

Background: The aim of this study is to characterize the patterns of loco-regional progression (LRP) and outcomes after definitive-dose intensity modulated radiation therapy (IMRT) for anaplastic thyroid cancer (ATC) with macroscopic neck disease at the time of IMRT.

Methods: Disease/treatment characteristics and outcomes for patients with unresected or incompletely resected ATC who received IMRT (≥45 Gy) were retrospectively reviewed. For those with LRP after IMRT, progressive/recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration. rGTVs were classified based on established spatial/dosimetric criteria.

Results: Forty patients treated between 2010-2020 formed …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Dedifferentiated Liposarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Experience, Madeline B Torres, Cheuk Hong Leung, Marianne Zoghbi, Rossana Lazcano, Davis Ingram, Khalida Wani, Emily Z Keung, M Alejandra Zarzour, Christopher P Scally, Kelly K Hunt, Anthony Conley, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan Farooqi, Devarati Mitra, Alison K Yoder, Michael S Nakazawa, Dejka Araujo, Andrew Livingston, Ravin Ratan, Shreyaskumar Patel, Vinod Ravi, Alexander J Lazar, Christina L Roland, Neeta Somaiah, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center.

Methods: We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Efficacy Of A Smartphone Application Assisting Home-Based Rehabilitation And Symptom Management For Patients With Lung Cancer Undergoing Video-Assisted Thoracoscopic Lobectomy: A Prospective, Single-Blinded, Randomised Control Trial (Popper Study, Chao Lv, Fangliang Lu, Xiugeng Zhou, Xiang Li, Wenhua Yu, Chune Zhang, Kaishen Chen, Songtao Du, Chao Han, Jia Wang, Yuzhao Wang, Shaolei Li, Liang Wang, Yinan Liu, Shanyuan Zhang, Miao Huang, Dongdong Song, Dachuan Zhao, Bing Liu, Yaqi Wang, Xinrun Cui, Zhiwei Zhou, Shi Yan, Nan Wu

Faculty, Staff and Student Publications

Background: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and postdischarge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation.

Methods: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. The authors screened 265 patients …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Utility Of Pre-Procedural [99mtc]Tcmaa Spect/Ct Multicompartment Dosimetry For Treatment Planning Of 90y Glass Microspheres In Patients With Hepatocellular Carcinoma: Comparison Of Anatomic Versus [99mtc]Tcmaa-Based Segmentation, Marnix Lam, Etienne Garin, Paul Haste, Alban Denys, Brian Geller, S Cheenu Kappadath, Cuneyt Turkmen, Daniel Y Sze, Hamad Saleh Alsuhaibani, Ken Herrmann, Marco Maccauro, Murat Cantasdemir, Matthew Dreher, Kirk D Fowers, Vanessa Gates, Riad Salem

Faculty, Staff and Student Publications

Purpose: Pre-treatment [99mTc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments.

Materials and methods: Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]TcMAA SPECT/CT. Logistic regression and …

Exposure Therapy Consortium: Outcomes Of The Proof-Of-Principle Study, Jasper A J Smits, Jonathan S Abramowitz, Rebecca A Anderson, Joanna J Arch, Daniel Badeja, Snir Barzilay, Amanda N Belanger, Thomas Borchert, Emma Bryant, Alane S Burger, Laura J Dixon, Christina D Dutcher, Hayley E Fitzgerald, Bronwyn M Graham, Anke Haberkamp, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, David Johnson, Baraa Q Kabha, Alex Kirk, Jürgen Margraf, Peter M Mcevoy, Bryan Mcspadden, Jill Newby, Michael W Otto, Santiago Papini, E Marie Parsons, Andre Pittig, Roxana Pittig, Winfried Rief, Svenja Schaumburg, Kiara R Timpano, Lena Waltemate, Andre Wannemüller, Cornelia Weise, Exposure Therapy Consortium

Faculty, Staff and Student Publications

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) …

Moderately Hypofractionated, Preoperative Radiotherapy In Patients With Soft Tissue Sarcomas (Hyport-Sts): Updated Local Control, Late Toxicities, And Patient-Reported Outcomes, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, David M Swanson, Caroline Hempel, Tiara Willis, Chris Pearlnath, Wei-Lien Wang, Ravin Ratan, Neeta Somaiah, Robert S Benjamin, Keila E Torres, Kelly K Hunt, Christopher P Scally, Emily Z Keung, Robert L Satcher, Justin E Bird, Patrick P Lin, Bryan S Moon, Valerae O Lewis, Christina L Roland, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

Background: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes.

Methods: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed …

Sex And Apoe Ε4 Allele Differences In Longitudinal White Matter Microstructure In Multiple Cohorts Of Aging And Alzheimer's Disease, Amalia Peterson, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Kacie D Deters, Niranjana Shashikumar, Kimberly R Pechman, Michael E Kim, Chenyu Gao, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Katherine A Gifford, Jo Ellen Wilson, Francis E Cambronero, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Mohamad Habes, Di Wang, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status.

Results: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.

Discussion: …

Consensus Guidelines For Delineation Of Clinical Target Volumes For Intensity Modulated Radiation Therapy For Intact Cervical Cancer: An Update, Emma C Fields, Walter R Bosch, Kevin V Albuquerque, Rohini Bhatia, Junzo Chino, Brandon Dyer, Beth Erickson, Denise Fabian, David Gaffney, Scott Glaser, Kathy Han, Lara Hathout, I-Chow Hsu, Naresh Jegadeesh, Jenna Kahn, Elizabeth Kidd, Ann Klopp, Eric Leung, Lilie Lin, Michelle Ludwig, Tianjun Ma, Loren Mell, Jyoti Mayadev, Ivy Petersen, Lorraine Portelance, Dominique Rash, Neil Taunk, Akila Viswanathan, Aaron Wolfson, Catheryn Yashar, Anamaria Yeung, Emi Yoshida, Christine M Fisher

Faculty, Staff and Student Publications

Purpose: Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques.

Methods and materials: Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) …

The Primary Cilia: Orchestrating Cranial Neural Crest Cell Development, Hiroyuki Yamaguchi, Matthew D Meyer, William B Barrell, Maryam Faisal, Rebecca Berdeaux, Karen J Liu, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Primary cilia (hereafter "cilia") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies. However, the detailed pathological mechanisms of craniofacial ciliopathies remain unclear. This perspective discusses our current understanding of the role of cilia in cranial neural crest cells. We also describe potential mechanisms of ciliogenesis in cranial neural crest cells, which may contribute to unraveling the complex pathogenesis of craniofacial ciliopathies.

Long-Term Follow-Up Of A Phase 2 Study Of All-Trans Retinoic Acid, Arsenic Trioxide, And Gemtuzumab Ozogamicin In Acute Promyelocytic Leukemia, Wei-Ying Jen, Jennifer Marvin-Peek, Hagop M Kantarjian, Yesid Alvarado, Gautam Borthakur, Elias Jabbour, William Wierda, Tapan M Kadia, Naval G Daver, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Steven Kornblau, Musa Yilmaz, Maro Ohanian, David Mccue, Jan Burger, Danielle Hammond, Keyur Patel, Ghayas C Issa, Naveen Pemmaraju, Koji Sasaki, Abhishek Maiti, Hussein A Abbas, Kelly Chien, Koichi Takahashi, Fadi Haddad, Prithviraj Bose, Lucia Masarova, Guillermo Montalban-Bravo, Mahesh Swaminathan, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.

Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence.

Results: …

Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio

Faculty, Staff and Student Publications

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strategies to manage therapy-induced immune dysfunction. This review also provides detailed information about the interactions between neutrophils and other immune elements …

Comprehensive Genomic Analysis Reveals Molecular Heterogeneity In Pediatric Alk-Positive Anaplastic Large Cell Lymphoma, Timothy I Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S Lim, Vasiliki Leventaki

Faculty, Staff and Student Publications

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription …

Global Research Trends And Focus On Immunotherapy For Endometrial Cancer: A Comprehensive Bibliometric Insight And Visualization Analysis (2012–2024), Yachen Xu, Tao Wang, Xiaojing Liang, Jie Yang, Yuxiang Zhang, Shan Bao

Faculty, Staff and Student Publications

Background: This study conducted a novel systematic bibliometric and visualization analysis of global literature on immunotherapy for endometrial cancer (EC) to explore dynamic trends, research hotspots, and emerging topics, providing valuable references for future research.

Methods: Articles and reviews on EC immunotherapy published between 2012 and August 2024 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric tools, CiteSpace and VOSviewer, were used to analyze clustering patterns and research dynamics.

Results: A total of 861 articles were contributed by 5,331 authors from 1,392 institutions across 58 countries or regions, involving 1,823 keywords. China demonstrated outstanding performance in this …

Long-Term Symptom Burden In A Young, Ambulatory Cohort After The Omicron Outbreak In China, Simeng Ren, Yumeng Tan, Hongkun Xu, Mian Wang, Rumei Xiang, Jiayue Jin, Baojin Han, Jiaheng Shi, Jingyu Zhang, Jinliang Yang, Xin Tian, Ying Li, Jiaojiao Chen, Wenzheng Zhang, Jingqi Yang, Xin Shelley Wang, Qiuling Shi, Jie Liu

Faculty, Staff and Student Publications

Introduction: At the end of 2022, an outbreak of the Omicron BF.7 and BA.5.2 subvariants of SARS-CoV-2 occurred in China. In this prospective cohort study, we investigated the pattern of development of major symptom burden and influencing factors in infected Chinese patients.

Methods: First-time infected outpatients were enrolled from December 7, 2022, to January 11, 2023 (N = 355). The prevalence of symptoms was monitored by a repeated patient-reported quantitative symptom survey over nine months.

Results: At the onset of the infection, the most prevalent symptoms (score ≥1 on a 0-10 numeric rating scale) were fatigue (91.8%), cough (91.8%), …

Characterization Of Additive Gene-Environment Interactions For Colorectal Cancer Risk, Claire E Thomas, Yi Lin, Michelle Kim, Eric S Kawaguchi, Conghui Qu, Caroline Y Um, Brigid M Lynch, Bethany Van Guelpen, Kostas Tsilidis, Robert Carreras-Torres, Franzel J B Van Duijnhoven, Lori C Sakoda, Peter T Campbell, Yu Tian, Jenny Chang-Claude, Stéphane Bézieau, Arif Budiarto, Julie R Palmer, Polly A Newcomb, Graham Casey, Loic Le Marchandz, Marios Giannakis, Christopher I Li, Andrea Gsur, Christina Newton, Mireia Obón-Santacana, Victor Moreno, Pavel Vodicka, Hermann Brenner, Michael Hoffmeister, Andrew J Pellatt, Robert E Schoen, Niki Dimou, Neil Murphy, Marc J Gunter, Sergi Castellví-Bel, Jane C Figueiredo, Andrew T Chan, Mingyang Song, Li Li, D Timothy Bishop, Stephen B Gruber, James W Baurley, Stephanie A Bien, David V Conti, Jeroen R Huyghe, Anshul Kundaje, Yu-Ru Su, Jun Wang, Temitope O Keku, Michael O Woods, Sonja I Berndt, Stephen J Chanock, Catherine M Tangen, Alicja Wolk, Andrea Burnett-Hartman, Anna H Wu, Emily White, Matthew A Devall, Virginia Díez-Obrero, David A Drew, Edward Giovannucci, Akihisa Hidaka, Andre E Kim, Juan Pablo Lewinger, John Morrison, Jennifer Ose, Nikos Papadimitriou, Bens Pardamean, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Xuechen Chen, Duncan C Thomas, Elizabeth A Platz, W James Gauderman, Ulrike Peters, Li Hsu

Faculty, Staff and Student Publications

Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

Results: There was no evidence of multiplicative interaction …

Integrative Multi-Omics Approach For Improving Causal Gene Identification, Austin King, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nisha Rathi, Nicole Hensch, Vera De La Cruz, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

Nrg Oncology White Paper On The Relative Biological Effectiveness In Proton Therapy, Harald Paganetti, Charles B Simone, Walter R Bosch, Daphne Haas-Kogan, David G Kirsch, Heng Li, Xiaoying Liang, Wei Liu, Anita Mahajan, Michael D Story, Paige A Taylor, Henning Willers, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Home Dialysis For Latinx Individuals Living With Kidney Failure: A Qualitative Study Of Interdisciplinary Dialysis Clinicians, Katherine Rizzolo, Rebeca Gonzalez Jauregui, Jade Teakell, Michel Chonchol, Sushrut S Waikar, Lilia Cervantes

Faculty, Staff and Student Publications

Key Points:

1. Individual-level advocacy to overcome structural barriers to home dialysis is key in improving home dialysis access for Latinx individuals.

2. Acknowledging patient influences on dialysis modality choice is critical for Latinx individuals with kidney failure.

3. Early, repeated education from a trusted source is important for Latinx individuals with kidney failure.

Background: Latinx individuals experience two times the incidence of kidney failure compared with non-Latinx individuals and are less likely to use home dialysis therapies. In this qualitative study, interdisciplinary home dialysis clinicians were interviewed to understand the key factors and strategies used by clinicians to improve home dialysis uptake …