Genetic Phenomena Commons^™

Associations Between Prostate Cancer And Dementia: A Nationwide Study In Sweden, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Jingkai Wei, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background and objective: Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.

Methods: To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998-2017 and 1 787 460 age-matched control men in Sweden without prior dementia. Cox regression was used to estimate hazard ratios (HRs) for Alzheimer's disease (AD) and vascular dementia (VaD) through 2018. Subanalyses explored differences by …

Celebrating The Fifth Edition Of The International Symposium On Fungal Stress – Isfus, A Decade After Its 2014 Debut, Alene Alder-Rangel, Amanda E A Rangel, Arturo Casadevall, Asiya Gusa, Chaoyang Xue, Charles M Boone, Chris Todd Hittinger, Claudio A Masuda, Consuelo Olivares-Yañez, Deborah Bell-Pedersen, Erica J Washington, Gerhard Braus, Guilhem Janbon, István Pócsi, Jason E Stajich, Jay C Dunlap, Joan W Bennett, Joseph Heitman, Ling Lu, Lucia Landi, Mari L Shinohara, Maurizio Del Poeta, Mavis A Acheampong, Mia R Maltz, Michael C Lorenz, Minou Nowrousian, N Louise Glass, Nichole A Broderick, Nicolás Pedrini, Nir Osherov, R Blake Billmyre, Sabrina Sarrocco, Salomé Leibundgut-Landmann, Vânia Aparecida Vicente, Xiaorong Lin, Xin-Qing Zhao, Yong-Sun Bahn, Zachary A Lewis, Drauzio E N Rangel

Faculty, Staff and Student Publications

The Fifth International Symposium on Fungal Stress (ISFUS) brought together in Brazil many of the leaders in the field of fungal stress responses, from fourteen countries, for four days of outstanding science ranging from basic research to studies with agricultural, medical, industrial, and environmental significance. In addition to the excellent oral and poster presentations, the Symposium organisers ensured that all participants had ample opportunity to engage, socialise, and network to exchange ideas and share research. The conference was enhanced by the world-class venue near Iguazu Falls, probably the greatest natural phenomenon in South America.

12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction And Microthrombi After Subarachnoid Hemorrhage In Mice, Ari Dienel, Sung Ha Hong, Hussein A Zeineddine, Sithara Thomas, Shafeeque C M, Dania A Jose, Kiara Torres, Jose Guzman, Andrew Dunn, P Kumar T, Gadiparthi N Rao, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus, 12/15-LOX is an important target to prevent delayed cerebral ischemia. SAH was induced in C57BL/6 and 12/15-LOX−/− mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed …

Human And Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition And Microglia-Dependent Plaque Response In Aged Mice, Juana Andreo-Lopez, Cristina Nuñez-Diaz, Kelly Do Huynh, Marie Minh Thu Nguyen, Celia Da Cunha, Francisco J Cantero-Molina, Cynthia Campos-Moreno, Stefania Zimbone, Francesco Bellia, Maria Laura Giuffrida, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Miriam Bettinetti-Luque, Nazaret Gamez, Catalina Valdes, Rodrigo Morales, Stefania Forner, Alessandra C Martini, Antonia Gutierrez, Frank M Laferla, David Baglietto-Vargas

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or "seeding" process. These Aβ and tau "seeds" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we employed histological and molecular approaches to determine whether seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates …

Cardiologists' Perceptions Of Cardiogenetic Testing And Management, W H Wilson Tang, Quan M Bui, Allison L Cirino, Lisa Dellefave-Castillo, Brendan J Floyd, Alejandra Guerchicoff, Marianna Guerchicoff, Amit V Khera, Joshua W Knowles, Kristen Lafayette, Andrew P Landstrom, Daria W Ma, Ana Morales, Kate M Orland, Daniel E Pineda-Alvarez, Siddharth K Prakash, Paul Theriot, Melissa Dempsey

Faculty, Staff and Student Publications

Background: Cardiogenetic testing has become clinically relevant as genetic insights increasingly contribute to the understanding and management of cardiovascular diseases of genetic origin. However, utilization of cardiogenetic testing remains variable and underutilized.

Objectives: The purpose of this study was to assess cardiologists' perceptions of cardiogenetic testing and identify relevant barriers, facilitators, educational needs, and clinical applications.

Methods: We surveyed 161 cardiologists using the American College of Cardiology CardioSurve Panel between March and April 2024.

Results: Among respondents, 80% reported that they have directly ordered or facilitated a referral for cardiogenetic testing for their patients. Generally, cardiologists from our testing group …

Consensus Statement On The Prevention And Management Of Complications Of Fully Ablative Laser Resurfacing Of The Face, Bianca Y Kang, Joel L Cohen, Roy Geronemus, Suzanne L Kilmer, Edward Victor Ross, Elizabeth L Tanzi, Jill S Waibel, Brian J F Wong, Murad Alam, Macrene Alexiades, Kenneth A Arndt, Mathew Avram, Ashish C Bhatia, Brian Stuart Biesman, Jason D Bloom, A Jay Burns, Henry H L Chan, Catherine M Digiorgio, Jeffrey S Dover, Sam Fathizadeh, Sara C Esteves, Michael H Gold, Gerald N Goldberg, Merete Haedersdal, Elika Hoss, Omar A Ibrahimi, H Ray Jalian, Kristen M Kelly, Woraphong Manuskiatti, Lisa A Marks, Girish S Munavalli, Jason N Pozner, Chris W Robb, Anthony M Rossi, Nazanin Saedi, Peter R Shumaker, Kelly Stankiewicz, Molly Wanner, Douglas C Wu, Adam J Wulkan, Arisa Ortiz

Faculty, Staff and Student Publications

Objectives: To achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face.

Materials and methods: Delphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9-point Likert scale (1 = strongly disagree; 9 = strongly agree) and …

Bayesian Counterfactual Machine Learning Individualizes Radiation Modality Selection To Mitigate Immunosuppression, Duo Yu, Michael J Kane, Yiqing Chen, Steven H Lin, Radhe Mohan, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.

Methods: A novel Bayesian causal inferential technique is introduced and applied to a matched retrospective cohort of 510 patients with esophageal cancer undergoing CRT to identify patient profiles …

Development Of A Multi-Institutional Dataset To Validate A Novel Inflammatory Breast Cancer Diagnostic Score, Filipa Lynce, Samuel M Niman, Megumi Kai, Sean Ryan, Elizabeth Troll, Li Li, Kathy D Miller, Reshma Jagsi, Ginny Mason, Beth A Overmoyer, H T Carisa Le-Petross, Faina Nakhlis, Savitri Krishnamurthy, Beth T Harrison, Susie X Sun, Eren D Yeh, Jennifer R Bellon, Laura E Warren, Michael C Stauder, Meredith M Regan, Wendy A Woodward

Faculty, Staff and Student Publications

Background: Susan G. Komen, the Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to propose novel quantitative scoring rubrics for IBC diagnosis. In this study, we developed a multi-institutional clinical dataset to test and validate the proposed scoring system.

Methods: IBC (N = 988) and non-IBC (N = 332) cases were identified at 2 institutions with dedicated multidisciplinary IBC programs. The non-IBC cohort included consecutive cT4b and cT4c patients. Standard operating procedures (SOPs) were developed for all ambiguous findings and languages. Three different methods were used for the imputation of missing data, …

Dynamic Long-Term Prediction With Intermediate Event Information: A Flexible Model With Bivariate Time-Varying Coefficients, Yunyi Wang, Wen Li, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

The integration of time-to-intermediate event data and the evolving characteristics of patients to enhance long-term prediction has garnered significant interest, driven by the wealth of data generated from longitudinal cohorts. In this paper, we propose sequential/dynamic prediction rules by using regression models with time-varying coefficients. We introduce a class of dynamic models that not only incorporates intermediate event information but also leverages information across different landmark times. To address the challenge of right-censoring, we employ an inverse weighting technique in the estimation process. We establish the asymptotic properties of the estimated parameters and conduct extensive simulations to assess the finite …

De-Escalating Local Therapies Without Compromising Outcomes: Lessons From The Collision Trial, Jessica Albuquerque, Noreen S Siddiqi, Van K Morris, Hop Tran Cao, Iwan Paolucci, Bruno C Odisio

Faculty, Staff and Student Publications

No abstract provided.

Isolation And Functional Properties Of Highly-Purified N-Terminal Domain Of Human Napi2b By Scalable “Resin Overload” Technique, Daria Savenkova, Irina Makarenko, Daria Nedorezova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Despite the enthusiasm and advances in the purification of native and engineered full-length membrane proteins, little attention has been paid to their fragments which could serve as attractive inspiration for function, regulation, or targeting of full-length membrane protein with therapeutic antibodies (Abs). Production of recombinant fragments of "therapeutic" membrane proteins for early-stage discovery research requires their purification to near homogeneity. It is important not only for the production of biotherapeutic antibodies but also for structural and functional studies of competitive protein-Abs, protein-protein, and lipid-protein interactions which heavily rely on the purity and quality of the isolated protein fragment of interest. …

Perioperative Durvalumab Plus Chemotherapy Plus New Agents For Resectable Non-Small-Cell Lung Cancer: The Platform Phase 2 Neocoast-2 Trial, Tina Cascone, Laura Bonanno, Florian Guisier, Amelia Insa, Moishe Liberman, Olivier Bylicki, Lorenzo Livi, Thomas Egenod, Romain Corre, Dong-Wan Kim, Maria Rosario Garcia Campelo, Mariano Provencio Pulla, Byoung Yong Shim, Giulio Metro, Jaafar Bennouna, Agata A Bielska, Alula R Yohannes, Yun He, Adam Dowson, Gozde Kar, Lara Mcgrath, Rakesh Kumar, Italia Grenga, Jonathan Spicer, Patrick M Forde

Faculty, Staff and Student Publications

In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA–IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody–drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) …

2025 European Leukemianet Recommendations For The Management Of Chronic Myeloid Leukemia, Jane F Apperley, Dragana Milojkovic, Nicholas C P Cross, Henrik Hjorth-Hansen, Andreas Hochhaus, Hagop Kantarjian, Jeffrey H Lipton, Hemant Malhotra, Dietger Niederwieser, Jerald Radich, Philippe Rousselot, Susanne Saussele, Charles A Schiffer, Richard Silver, Simona Soverini, Leif Stenke, Anna Turkina, Luis Felipe Casado, Fausto Castagnetti, Francisco Cervantes, Richard E Clark, Jorge Cortes, Michael Deininger, Timothy P Hughes, Jeroen Janssen, Qian Jiang, Dong-Wook Kim, Richard A Larson, Francois X Mahon, Michael Mauro, Jiri Mayer, Franck E Nicolini, Fabrizio Pane, Delphine Rea, Johan Richter, Gianantonio Rosti, Giuseppe Saglio, Rüdiger Hehlmann

Faculty, Staff and Student Publications

In this 5th version of the European LeukemiaNet guidance for adult patients, there are important changes in several areas of management based on evidence available since 2020, including the World Health Organisation's reclassification of CML as a biphasic disease. Previous advice to switch the tyrosine kinase inhibitor (TKI) on failure of molecular milestones, is modified to better account for individual patient circumstances. Our recommendations are summarized in tables designed to be read in conjunction with the text which offers justification and additional advice. We describe decision-making for first-line treatment, both in available drugs and their initial dosing. Similarly we elaborate …

Addressing Challenges In Developing Treatments For Inherited Retinal Diseases: Recommendations From The Third Monaciano Symposium, Debra A Thompson, K Thiran Jayasundera, Oleg Alekseev, Robin R Ali, Alessia Amato, Vadim Y Arshavsky, Isabelle S Audo, Alberto Auricchio, James W B Bainbridge, Eyal Banin, Cagri G Besirli, David G Birch, Kari E Branham, Artur V Cideciyan, Stephen P Daiger, Jacque L Duncan, Abigail T Fahim, John G Flannery, Roberto Gattegna, John R Heckenlively, Elise Héon, Alessandro Iannaccone, Naheed W Khan, Samer Khateb, Henry J Klassen, Bart P Leroy, Dario Marangoni, Michel Michaelides, David C Musch, Mark E Pennesi, Simon M Petersen-Jones, Eric A Pierce, Rajesh C Rao, José-Alain Sahel, Paul A Sieving, Enrica Strettoi, Cameron R Strong, Thomas J Wubben, Paul Yang, David N Zacks

Faculty, Staff and Student Publications

Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to provide safe and effective therapies for these rare conditions. Although several ongoing programs remain poised for success, numerous challenges have negatively impacted the ability to obtain regulatory approvals. The present position paper briefly summarizes recent advances and challenges in developing therapeutics for inherited retinal diseases, and presents a set of recommendations for moving the field forward. The priorities identified are discussed in terms of progress …

A Phase 2 Trial Of Cpx-351 Combined With Venetoclax In Relapsed Or Refractory Acute Myeloid Leukemia, Tapan M Kadia, Wei-Ying Jen, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Elias Jabbour, Wei Qiao, Nicholas J Short, Koichi Takahashi, Ghayas C Issa, Courtney D Dinardo, Guillermo Montalban-Bravo, Naveen Pemmaraju, Andrew Tran, Vanthana Bharathi, Sanam Loghavi, Amin M Alousi, Uday Popat, Naval G Daver, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Master Protocol Design With Hybrid Control For Efficient Early-Phase Trial Consolidation, Alexander M Kaizer, Xiaojiang Zhan, Eric Baron, Rui Sammi Tang, David S Hong, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Master protocols represent transformations, enabling multiple therapies or diseases under a single protocol. These designs streamline therapeutic development by reducing redundancies. Suited for evolving fields such as oncology and global emergencies such as the COVID-19 pandemic, master protocols have been exemplified by studies such as RECOVERY, Solidarity, and I-SPY 2, which accelerated effective treatment identification (with I-SPY 2 focused on molecular subtypes). Recent oncology examples, such as MORPHEUS, evaluate immunotherapy combinations with shared controls. Despite advantages, their application in early-phase oncology remains underutilized amid growing regulatory emphasis on randomization for robust evidence.

Methods: US Food and Drug Administration (FDA) …

Film Measurements Of Kilovoltage X-Ray Percentage Depth Doses For Different Energies And Field Sizes, Tze Yee Lim, Dershan Luo, Jamshid Moradi-Kurdestany, Xin Wang, Ramesh Tailor

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Objectives: Kilovoltage x-ray therapy, which includes superficial x-rays and orthovoltage x-rays, is particularly suited for treatments near the skin surface. Radiation dose deposition at depth is typically characterized by percentage depth dose (PDD) curves. However, PDD data are difficult to obtain in kilovoltage x-ray therapy, hence clinics often rely on British Journal of Radiology Supplement 25 (BJR-25) archival data. This study measured PDD for different energies and field sizes on the Xstrahl 300 kilovoltage x-ray therapy unit for comparison with BJR-25 data.

Methods: We irradiated EBT3 film in water using different energy and field size combinations, then, compared the acquired …

Orp2 Regulates Free Cholesterol Accumulation In Hepatocytes During Mash, Jin Wu, Yudi Zhao, Liwen Qiu, Qiaoli Chen, Xiaowei Wang, Jingwen Gu, Yan Liang, Yingjie Zhang, Hong-Yu Wang, Yang Liu, Xiaoqin Wu, Shuai Chen, Feng-Jung Chen, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

Background: Cholesterol crystals in hepatocytes are known to strongly associate with human metabolic dysfunction-associated steatohepatitis. However, it remains unclear which molecular pathway(s) regulates free cholesterol accumulation and the formation of cholesterol crystals in hepatocytes. In cultured cell lines, oxysterol-binding protein-related protein 2 (ORP2) functions to deliver cholesterol to the plasma membrane from endosomal compartments.

Methods: Here, we generated liver-specific ORP2 knockout (ORP2-LKO) mice and characterized their metabolic phenotypes on chow and high-fat diet.

Results: The ORP2-LKO mice developed much more severe hepatic steatosis than floxed control mice after high-fat diet feeding. They also demonstrated more severe liver inflammation and damage. …

Excellent Response Following Palliative Radiation For Locally Advanced Epidemic/Aids-Associated Kaposi Sarcoma Of The Lower Extremity: A Case Report, Anushka S Mandalapu, Alison K Yoder, Xin Wang, Devarati Mitra, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan S Farooqi

Faculty, Staff and Student Publications

No abstract provided.

Patient, Physician, And Assessor Blinding In Phase Iii Randomized Trials In Oncology: A Meta-Epidemiological Analysis, Gabrielle Brown, Pavlos Msaouel, Avital M Miller, Ramez Kouzy, Timothy A Lin, Joseph Abi Jaoude, Ethan B Ludmir, Alexander D Sherry

Faculty, Staff and Student Publications

Background: Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression-free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints.

Methods: Two-arm, superiority-design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.gov with no date limitation. Trials were required to have a PFS primary endpoint. The study outcomes were the presence of double-blind designs and blinded independent central review (BICR) for the primary endpoint. Ninety-five percent credible intervals for binary outcomes were estimated from beta distributions, and multivariable logistic …

Single-Cell Proteomic Analysis Reveals Multiple Myeloma Heterogeneity And The Dynamics Of The Tumor Immune Microenvironment In Precursor And Advanced States, Mohamed Kamal, Stephanie N Shishido, Jeremy Mason, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) is an aggressive hematologic malignancy arising from plasma cell (PC) proliferation in the bone marrow, progressing from its precursor states MGUS and SMM. Despite therapeutic advances, MM remains incurable, underscoring the need for better risk stratification and early detection. Tumor heterogeneity and dynamic immune microenvironment changes drive progression, yet bulk analyses overlook rare subpopulations critical to disease evolution and resistance. This study employed multiplexed targeted proteomics to characterize bone marrow aspirates (BMA) from 22 patients to observe the change in the distribution of PCs and tumor immune microenvironment (TiME) cells across MM disease states and controls. Bone …

Acquired Resistance In Cancer: Towards Targeted Therapeutic Strategies, Alice Soragni, Erik S Knudsen, Thomas N O'Connor, Cristina E Tognon, Jeffrey W Tyner, Beatrice Gini, Donghwa Kim, Trever G Bivona, Xingxing Zang, Agnieszka K Witkiewicz, David W Goodrich, Dadi Jiang, Seth T Gammon, Christopher D Willey, Paul C Boutros, Vlad C Sandulache, Abdullah A Osman, Jeffrey N Myers, Kamiya Mehla, Pankaj K Singh, Keith S Chan, Hongbo Gao, Himangi Marathe

Faculty, Staff and Student Publications

Development of acquired therapeutic resistance limits the efficacy of cancer treatments and accounts for therapeutic failure in most patients. How resistance arises, varies across cancer types and differs depending on therapeutic modalities is incompletely understood. Novel strategies that address and overcome the various and complex resistance mechanisms necessitate a deep understanding of the underlying dynamics. We are at a crucial time when innovative technologies applied to patient-relevant tumour models have the potential to bridge the gap between fundamental research into mechanisms and timing of acquired resistance and clinical applications that translate these findings into actionable strategies to extend therapy efficacy. …

Provider Attitudes And Perspectives On Rehabilitation For Pediatric Cancer Patients, Maria C Swartz, Eduardo Gonzalez Villarreal, Keri Schadler, Donna Kelly, Alakh P Rajan, Clark Andersen, Shiming Zhang, Stephanie J Wells, Amy Heaton, Karen M Moody

Faculty, Staff and Student Publications

PurposeTwenty percent of childhood cancer survivors experience physical function impairments, and ∼75% develop a chronic health condition. Physical and occupational therapists (PT/OTs) can mitigate these late effects, yet few children receive cancer rehabilitation (CR). This research aimed to identify provider attitudes and perspectives towards CR services for children across inpatient and outpatient settings at a cancer center.MethodsThree cardiac rehabilitation instruments were adapted to evaluate knowledge, attitudes, and perceptions regarding CR delivery. Descriptive statistics were used to summarize participant survey results.ResultsTwenty administrators, 20 physicians/advanced practice providers (APPs), and 20 PT/OTs completed surveys. All disciplines strongly agreed on the value of CR …

Author Correction: The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

No abstract provided.

The Significance Of Detecting An Unusual Myeloblast Immunophenotype In A Presumptive Clinical Diagnosis Of Myelodysplastic Syndromes, Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but …

Bard: A Seamless Two-Stage Dose Optimization Design Integrating Backfill And Adaptive Randomization, Yixuan Zhao, Rachael Liu, Jianchang Lin, Ying Yuan

Faculty, Staff and Student Publications

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose, followed by a randomization stage where patients are assigned to two or more doses to further assess and compare their risk-benefit profiles to identify the optimal dose. A limitation of this approach is its requirement for a relatively large sample size. To address this challenge, we propose a seamless two-stage design, BARD (Backfill and Adaptive Randomization for Dose Optimization), which incorporates two key features to reduce sample size and shorten trial duration. The first feature is the integration of …

Characterization Of The Germline Pathogenic Mutational Landscape And Oncologic Outcomes Among 877 Patients With Invasive Lobular Carcinoma, Victoria D Huynh, Jason Mouabbi, Henry M Kuerer, Kerollos Nashat Wanis, Hiam M Abdel-Salam, Angelica M Gutierrez, Helen M Johnson, Anthony Lucci, Kelly K Hunt, Banu K Arun

Faculty, Staff and Student Publications

Purpose: There is a paucity of literature on germline pathogenic variants (gPVs) in patients with invasive lobular carcinoma (ILC). This study characterizes the landscape and compares clinicopathologic variables and treatment outcomes between those with and without gPVs.

Methods: A prospectively maintained institutional database was used to identify all patients diagnosed with nonmetastatic ILC who had germline genetic testing. Clinicopathologic characteristics and time to recurrence, contralateral cancer, and death were compared for patients with and without gPVs. Conditional hazard ratios, computed by Cox proportional hazards models, described associations between clinicopathologic factors, including gPV status, and cancer events.

Results: Of 4398 patients …

Computed Tomography Radiomics-Based Cross-Sectional Detection Of Mandibular Osteoradionecrosis In Head And Neck Cancer Survivors, Serageldin Kamel, Laia Humbert-Vidan, Zaphanlene Kaffey, Sarah Mirbahaeddin, Abdulrahman Abusaif, David T A Fuentes, Kareem Wahid, Cem Dede, Mohamed A Naser, Renjie He, Ahmed W Moawad, Khaled M Elsayes, Melissa M Chen, Adegbenga O Otun, Jillian Rigert, Mark S Chambers, Andrew Hope, Erin Watson, Kristy K Brock, Katherine Hutcheson, Lisanne Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Abdallah S R Mohamed, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

Purpose: This study aims to identify radiomic features from contrast-enhanced CT (CECT) scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in head and neck cancer (HNC) patients treated with radiotherapy (RT).

Materials and methods: CECT images from 150 patients with confirmed ORN diagnosis (2008-2018) at MD Anderson Cancer Center (MDACC) were analyzed (80 % train, 20 % test). Radiomic features were extracted using PyRadiomics from manually segmented ORN regions and automated contralateral healthy mandible regions. Correlation analysis (r > 0.95) reduced features for model training. A random Forest (RF) classifier with Recursive Feature Elimination identified discriminative features. Explainability was assessed …

Management Of Aromatase Inhibitor-Associated Bone Loss (Aibl) In Women With Hormone-Sensitive Breast Cancer: An Updated Joint Position Statement Of The Iof, Cabs, Ects, Ieg, Esceo, Ims, And Siog, Peyman Hadji, Matty Aapro, Nasser Al-Dagri, Majed Alokail, Emmanuel Biver, Jean-Jacques Body, Maria Luisa Brandi, Janet Brown, Cyrille Confavreux, Bernard Cortet, Matthew Drake, Peter Ebeling, Erik Fink Eriksen, Ghada El-Hajj Fuleihan, Theresa A Guise, Nick C Harvey, Andreas Kurth, Bente Langdahl, Willem Lems, Radmila Matijevic, Eugene Mccloskey, Rossella Nappi, Santiago Palacios, Georg Pfeiler, Jean-Yves Reginster, René Rizzoli, Daniele Santini, Sansin Tuzun, Catherine Van Poznak, Tobias De Villiers, M Carola Zillikens, Robert Coleman

Faculty, Staff and Student Publications

Background: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.

Patients and methods: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the …