Medical Specialties Commons^™

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

Faculty, Staff and Student Publications

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Artificial Intelligence Uncertainty Quantification In Radiotherapy Applications – A Scoping Review, Kareem A Wahid, Zaphanlene Y Kaffey, David P Farris, Laia Humbert-Vidan, Amy C Moreno, Mathis Rasmussen, Jintao Ren, Mohamed A Naser, Tucker J Netherton, Stine Korreman, Guha Balakrishnan, Clifton D Fuller, David Fuentes, Michael J Dohopolski

Faculty, Staff and Student Publications

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.

Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual …

Improved Robustness For Deep Learning-Based Segmentation Of Multi-Center Myocardial Perfusion Cardiovascular Mri Datasets Using Data-Adaptive Uncertainty-Guided Space-Time Analysis., Dilek M Yalcinkaya, Khalid Youssef, Bobak Heydari, Janet Wei, C Noel Bairey Merz, Robert Judd, Rohan Dharmakumar, Orlando P Simonetti, Jonathan W Weinsaft, Subha V Raman, Behzad Sharif

Heart and Vascular Articles

BACKGROUND: Fully automatic analysis of myocardial perfusion cardiovascular magnetic resonance imaging datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge.

METHODS: Datasets from three medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models …

Hypoalbuminemia In Children With Acute Lymphoblastic Leukemia: Relation To Asparaginase Therapy And Impact On High Dose Methotrexate Elimination., Sophie Rex Christensen, Christina Friis Jensen, Jesper Heldrup, Zachary Taylor, Laura Ramsey, Steen Rosthøj

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: High-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor.

METHODS: To examine the impact of serum albumin we reviewed 325 HDMTX 5 g/m2 courses in a cohort of 51 children treated on the NOPHO ALL 2008 protocol, dividing the courses into four groups with different levels of baseline albumin (A < 25 g/L, B 25-29 g/L, C 30-34 g/L and D ≥ 35 g/L).

RESULTS: Hypoalbuminemia was present in 51% of the courses, mostly in the early phases of chemotherapy while …

Azacitidine As Epigenetic Priming For Chemotherapy Is Safe And Well-Tolerated In Infants With Newly Diagnosed Kmt2a-Rearranged Acute Lymphoblastic Leukemia: Children's Oncology Group Trial Aall15p1, Erin M. Guest, John A Kairalla, Meenakshi Devidas, Emily Hibbitts, Andrew J. Carroll, Nyla A. Heerema, Holly R. Kubaney, Margaret A. August, Sidharth Ramesh, Byunggil Yoo, Midhat S. Farooqi, Melinda G. Pauly, Daniel S. Wechsler, Rodney R. Miles, Joel M. Reid, Cynthia D. Kihei, Lia Gore, Elizabeth A. Raetz, Stephen P. Hunger, Mignon L. Loh, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of failure to achieve remission, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children's Oncology Group trial AALL15P1 tested the safety and tolerability of 5 days of azacitidine treatment immediately prior to the start of chemotherapy on day 6, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was well-tolerated, with only …

Responding To The Workforce Crisis: Consensus Recommendations From The Second Workforce Summit Of The American Society Of Pediatric Nephrology., Danielle E. Soranno, Sandra Amaral, Isa Ashoor, Meredith A. Atkinson, Gina-Marie Barletta, Michael C. Braun, Joann Carlson, Caitlin Carter, Annabelle Chua, Vikas R. Dharnidharka, Keri Drake, Elif Erkan, Dan Feig, Stuart L. Goldstein, David Hains, Lyndsay A. Harshman, Elizabeth Ingulli, Alexander J. Kula, Mary Leonard, Sudha Mannemuddhu, Shina Menon, Zubin J. Modi, Marva Moxey-Mims, Arwa Nada, Victoria Norwood, Michelle C. Starr, Priya S. Verghese, Darcy K. Weidemann, Adam Weinstein, Jodi Smith

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.

OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.

EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …

High Activity Of The New Myeloablative Regimen Of Gemcitabine/Clofarabine/Busulfan For Allogeneic Transplant For Aggressive Lymphomas, Jeremy Ramdial, Ruitao Lin, Peter F Thall, Benigno C Valdez, Chitra Hosing, Samer Srour, Uday Popat, Muzaffar Qazilbash, Amin Alousi, Melissa Barnett, Alison Gulbis, Terri Lynn Shigle, Elizabeth J Shpall, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically. Eligibility: age 12-65, refractory aggressive B-NHL, T-NHL or Hodgkin, with a matched donor. Infusional Gem was dose-escalated on days (d) -6 and -4 (475-975 mg/m2/day), followed by Clo (40 mg/m2/day) and Bu (target AUC, 4000 μMol min/day) (d -6 to -3). CD20+ tumors received rituximab. GVHD prophylaxis …

Cutaneous T Cell Lymphoma Atlas Reveals Malignant Th2 Cells Supported By A B Cell-Rich Tumor Microenvironment, Ruoyan Li, Johanna Strobl, Elizabeth F M Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A Botting, Nina Zila, Elena Prigmore, Nusayhah H Gopee, Marta A Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M Bacon, Sophie C Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J Reynolds, Judith E Allen, Constanze Jonak, Patrick M Brunner, Sarah A Teichmann, Muzlifah Haniffa

Faculty, Staff and Student Publications

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that …

Anti-Programmed Death Ligand 1 Plus Targeted Therapy In Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial, Maria E Cabanillas, Ramona Dadu, Renata Ferrarotto, Maria Gule-Monroe, Suyu Liu, Bryan Fellman, Michelle D Williams, Mark Zafereo, Jennifer R Wang, Charles Lu, Matthew Ning, Brian A Mckinley, Scott E Woodman, Dzifa Duose, Gary B Gunn, Naifa L Busaidy, Rare Tumor Initiative Team

Faculty, Staff and Student Publications

Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.

Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).

Design, setting, and participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus …

Improving The Clinical Meaning Of Surrogate Endpoints: An Empirical Assessment Of Clinical Progression In Phase Iii Oncology Trials, Alexander D Sherry, Timothy A Lin, Zachary R Mccaw, Esther J Beck, Ramez Kouzy, Joseph Abi Jaoude, Adina H Passy, Avital M Miller, Gabrielle S Kupferman, Clifton David Fuller, Charles R Thomas, Eugene J Koay, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable …

Association Between Socioeconomic Disadvantage And Risks Of Early And Recurrent Admissions Among Patients With Newly Diagnosed Heart Failure, Radha Dhingra, Hanzhang Xu, Bradley G Hammill, Scott M Lynch, Jessica S West, Michael D Green, Eric D Peterson, Lesley H Curtis, Matthew E Dupre

Faculty, Staff and Student Publications

Background: Socioeconomic disadvantage is associated with greater risks of hospital readmission and mortality among patients with heart failure (HF). However, it is less clear whether socioeconomic disadvantage has an immediate and lasting impact on the risk of admissions after the diagnosis of HF.

Methods: We used electronic health record data of patients aged 65 years and older with newly diagnosed HF between January 2015 and July 2018 in the Duke University Health System, with up to 8 years of follow-up. We assessed the association between neighborhood-level disadvantage, measured by the area deprivation index (lower, moderate, or higher) and hospital admissions …

Defining Breast Cryoablation Treatment Success: A Guide For The Curative And Palliative Treatment Of Breast Cancer, Monica L Huang, Deanna L Lane, Lauren Q Chang Sen, Rosalind P Candelaria, Henry M Kuerer, Kelly K Hunt, Catherine Akay, Bora Lim, Simona Shaitelman, Rosa F Hwang, Hui Chen, Rajani Katta, Lumarie Santiago

Faculty, Staff and Student Publications

Rationale and objectives: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives.

Materials and methods: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, …

Sleep Disturbances Based On Patient Reported Outcomes In Patients With Breast Cancer, Saadia A Faiz, Ashley S Knox, Bryan Fellman, Bibi Aneesah Jaumally, G Nancy Pacheco, Aneesa Das, Reeba Mathew, Rashmi Murthy, Jennifer K Litton, Diwakar D Balachandran, Lara Bashoura

Faculty, Staff and Student Publications

Purpose: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders.

Methods: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed. Clinical characteristics, PROs using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and PSG data were reviewed.

Results: 404 patients were identified with 43% early, 30% locally advanced and 17% metastatic disease. PSQI revealed poor sleep in 75%, and ESS …

Cams In Command: Aging Brain Macrophages Fine-Tune Stroke Immune Responses, Rodney M Ritzel, Danye Jiang, Louise D Mccullough

Faculty, Staff and Student Publications

Central nervous system-associated macrophages (CAMs) are a unique subset of immune cells located at the interface between the blood and the brain parenchyma. In a recent study in mice, Levard and colleagues found that CAMs regulate immune cell trafficking, endothelial activation, and antigen presentation following stroke exclusively in aged animals, underscoring the importance of using translationally relevant models for studying age-related diseases.

Redox Regulation Of Proteostasis, Long Duy Duong, James D West, Kevin A Morano

Faculty, Staff and Student Publications

Oxidants produced through endogenous metabolism or encountered in the environment react directly with reactive sites in biological macromolecules. Many proteins, in particular, are susceptible to oxidative damage, which can lead to their altered structure and function. Such structural and functional changes trigger a cascade of events that influence key components of the proteostasis network. Here, we highlight recent advances in our understanding of how cells respond to the challenges of protein folding and metabolic alterations that occur during oxidative stress. Immediately after an oxidative insult, cells selectively block the translation of most new proteins and shift molecular chaperones from folding …

Outcomes Of Mechanical Thrombectomy In Anticoagulated Patients With Acute Distal And Medium Vessel Stroke, Hamza Salim, Basel Musmar, Nimer Adeeb, Vivek Yedavalli, Dhairya Lakhani, Sahibjot Singh Grewal, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw, Mad Mt Investigators

Faculty, Staff and Student Publications

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood.

Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, …

Evaluating Novel In Silico Tools For Accurate Pathogenicity Classification In Epilepsy-Associated Genetic Missense Variants, Ludovica Montanucci, Tobias Brünger, Christian M Boßelmann, Alina Ivaniuk, Eduardo Pérez-Palma, Samden Lhatoo, Costin Leu, Dennis Lal

Faculty, Staff and Student Publications

Objective: Determining the pathogenicity of missense variants in clinical genetic tests for individuals with epilepsy is crucial for guiding personalized treatment. However, achieving a definitive pathogenic classification remains challenging, with most missense variants still classified as variants of uncertain significance (VUS) and with the availability of many computational tools which may provide conflicting predictions. Here, we aim to evaluate the performance of state-of-the-art computational tools in pathogenicity prediction of missense variants in epilepsy-associated genes. This will assist in selecting the most appropriate tool and critically assess their use in clinical setting.

Methods: We assessed the performance of nine in silico …

Research Prioritization In Hernia Surgery: A Modified Delphi Achqc And Vhoc Expert Consensus, Daphne Remulla, Mazen R Al-Mansour, Christopher Schneider, Sharon Phillips, William W Hope, Joel F Bradley Iii, Richard A Pierce, Luis Arias-Espinosa, Karla Bernardi, Julie L Holihan, Michelle Loor, Mike K Liang, Benjamin T Miller

Faculty, Staff and Student Publications

Purpose: Numerous clinical practice guidelines and consensus statements have been published in hernia surgery, however, there is still a need for high-quality evidence to address remaining unanswered questions. The aim of this study was to conduct research priority setting through a modified Delphi process to identify a list of top research priorities in hernia surgery.

Methods: A structured literature review of clinical practice guidelines was performed by the steering committee. Topics considered clinically significant, practical to study and lacking strong evidence were extracted and refined into a comprehensive list, then entered into a two-round Delphi survey for prioritization at the …

Prediction Of Pathological Complete Response To Chemotherapy For Breast Cancer Using Deep Neural Network With Uncertainty Quantification, Bowen Jing, Kai Wang, Erich Schmitz, Shanshan Tang, Yunxiang Li, You Zhang, Jing Wang

Faculty, Staff and Student Publications

Background: The I-SPY 2 trial is a national-wide, multi-institutional clinical trial designed to evaluate multiple new therapeutic drugs for high-risk breast cancer. Previous studies suggest that pathological complete response (pCR) is a viable indicator of long-term outcomes of neoadjuvant chemotherapy for high-risk breast cancer. While pCR can be assessed during surgery after the chemotherapy, early prediction of pCR before the completion of the chemotherapy may facilitate personalized treatment management to achieve an improved outcome. Notably, the acquisition of dynamic contrast-enhanced magnetic resonance (DCEMR) images at multiple time points during the I-SPY 2 trial opens up the possibility of achieving early …

Excess Risk Of Chronic Health Conditions In Black Adolescent And Young Adult Cancer Survivors, Amy M Berkman, Eunju Choi, Christabel K Cheung, John M Salsman, Susan K Peterson, Clark R Andersen, Qian Lu, J A Livingston, Aryce Battle, Michelle A T Hildebrandt, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Background: The US population of adolescent and young adult (age 15-39 years at diagnosis) cancer survivors is growing. Previous studies have identified racial and ethnic disparities in survival and health outcomes in racially minoritized survivors, including Black survivors, compared with White survivors. However, comparisons should be made between those of the same race or ethnicity with and without a history of AYA cancer to fully understand the association of a cancer diagnosis with socioeconomic status (SES) and health outcomes within a minoritized population.

Methods: Non-Hispanic Black AYA cancer survivors and non-Hispanic Black age- and sex-matched controls were identified from self-reported …

Drug And Biomarker Tissue Levels In A Randomized Presurgical Trial On Exemestane Alternative Schedules, Davide Serrano, Harriet Johansson, Bjørn-Erik Bertelsen, Sara Gandini, Gunnar Mellgren, Parijatham Thomas, Katherine D Crew, Nagi B Kumar, Debora Macis, Valentina Aristarco, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Mauro D'Amico, Tania Buttiron-Webber, Irene Maria Briata, Stefano Spinaci, Viviana Galimberti, Lana A Vornik, Eduardo Villar-Sanchez, Powel H Brown, Brandy M Heckman-Stoddard, Eva Szabo, Bernardo Bonanni, Andrea Decensi

Faculty, Staff and Student Publications

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a presurgical study of alternative exemestane schedules. Postmenopausal women candidates for breast surgery for estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg once daily (QD), 25 mg 3 times/week (TIW), or 25 mg per week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the …

Association Between Chronotype And Chronic Neuropathic Pain Sensitivity: A Pilot Prospective, Observational, Single-Center, Cross-Sectional Study, Michael Kim, Yuri C Martins, Kishan Patel, Chiu-Hsieh Hsu, Mohab Ibrahim, Vasudha Goel, Amol M Patwardhan, Sejal Jain

Faculty, Staff and Student Publications

Background: Chronotype defines an organism's biological preference for timing of activity and sleep. Being a morning chronotype (i.e., tending to wake up early and go to bed earlier at night) is associated with protection against chronic musculoskeletal pain and headaches, but the relationship between chronotype and neuropathic pain sensitivity remains unclear.

Objectives: The aim of this pilot study was to explore the relationship among chronotype, neuropathic pain sensitivity, and pain interference in patients with chronic neuropathic pain disorders.

Study design: This was a prospective, observational, single-center, cross-sectional study.

Setting: Patients were recruited from pain management clinics.

Methods: The Morningness-Eveningness Questionnaire …

Datopotamab-Deruxtecan In Early-Stage Breast Cancer: The Sequential Multiple Assignment Randomized I-Spy22 Phase 2 Trial, Katia Khoury, Jane L Meisel, Christina Yau, Hope S Rugo, Rita Nanda, Marie Davidian, Butch Tsiatis, A Jo Chien, Anne M Wallace, Mili Arora, Mariya Rozenblit, Dawn L Hershman, Alexandra Zimmer, Amy S Clark, Heather Beckwith, Anthony D Elias, Erica Stringer-Reasor, Judy C Boughey, Chaitali Nangia, Christos Vaklavas, Coral Omene, Kathy S Albain, Kevin M Kalinsky, Claudine Isaacs, Jennifer Tseng, Evanthia T Roussos Torres, Brittani Thomas, Alexandra Thomas, Amy Sanford, Ronald Balassanian, Cheryl Ewing, Kay Yeung, Candice Sauder, Tara Sanft, Lajos Pusztai, Meghna S Trivedi, Ashton Outhaythip, Wen Li, Natsuko Onishi, Adam L Asare, Philip Beineke, Peter Norwood, Lamorna Brown-Swigart, Gillian L Hirst, Jeffrey B Matthews, Brian Moore, W Fraser Symmans, Elissa Price, Carolyn Beedle, Jane Perlmutter, Paula Pohlmann, Rebecca A Shatsky, Angela Demichele, Douglas Yee, Laura J Van 'T Veer, Nola M Hylton, Laura J Esserman

Faculty, Staff and Student Publications

Among the goals of patient-centric care are the advancement of effective personalized treatment, minimising toxicity. The phase-2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimising individual outcomes. Here we tested datopotamab-deruxtecan (Dato-Dxd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomisation trial (SMART) design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent (Block A), a taxane-based regimen tailored to the tumour subtype (Block B), and doxorubicin/cyclophosphamide (Block C). Patients are randomised into …

Keratinocyte Carcinomas In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Christina Boull, Yan Chen, Cindy Im, Alan Geller, Yadav Sapkota, James E Bates, Rebecca Howell, Michael A Arnold, Miriam Conces, Louis S Constine, Leslie Robison, Yutaka Yasui, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established.

Objective: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS.

Methods: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed < 21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics.

Results: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted …

A Multiple X-Ray-Source Array (Mxa) System With A Planar Two-Dimensional Source Distribution For Digital Breast Tomosynthesis, Alejandro Sisniega, Andrew M Hernandez, Shadi A Shakeri, Elizabeth A Morris, John M Boone, Jeffrey H Siewerdsen, Paul R Schwoebel

Faculty, Staff and Student Publications

Background: Digital breast tomosynthesis (DBT) has outpaced digital mammography in clinical adoption in the United States; however, substantial technological limitations remain to image quality in DBT, including undersampling from a one-dimensional (1D) scan geometry, x-ray source motion during acquisition, and patient motion artifacts from long exam times.

Purpose: A thermionic cathode x-ray system employing two-dimensional (2D, planar) multiple x-ray-source arrays (MXA) is proposed to improve DBT image quality.

Methods: A 1D MXA, consisting of a linear array of thermionic cathodes was used to simulate a 2D MXA. The 1D MXA included 11 focal spots separated by a distance of Δd …

Radiation-Induced Macrovessel/Microvessel Disease, Jun-Ichi Abe, Bryan G Allen, Andreas M Beyer, David Lewandowski, Kranti A Mapuskar, Vikram Subramanian, Michelle R Tamplin, Isabella M Grumbach

Faculty, Staff and Student Publications

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from …

Safety And Clinical Outcomes Of Endovascular Therapy Versus Medical Management In Late Presentation Of Large Ischemic Stroke, Adnan Mujanovic, Daniel Strbian, Jelle Demeestere, João Pedro Marto, Volker Puetz, Raul G Nogueira, Mohamad Abdalkader, Simon Nagel, Jean Raymond, Marc Ribo, Patrik Michel, Shinichi Yoshimura, Osama O Zaidat, Simon Winzer, Santiago Ortega-Gutierrez, Sunil A Sheth, James E Siegler, Anne Dusart, Diogo C Haussen, Hilde Henon, Bettina L Serrallach, Mahmoud H Mohammaden, Markus A Möhlenbruch, Marta Olive-Gadea, Ajit S Puri, Nobuyuki Sakai, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Tomas Dobrocky, Nicolas Martinez-Majander, Stefania Nannoni, Flavio Bellante, Aaron Rodriguez-Calienes, Sergio Salazar-Marioni, Pekka Virtanen, Daniel Po Kaiser, Rita Ventura, Jessica Jesser, Alicia C Castonguay, Muhammad M Qureshi, Hesham E Masoud, Milagros Galecio-Castillo, Manuel Requena, Riikka Lauha, Wei Hu, Eugene Lin, Zhongrong Miao, Daniel Roy, Hiroshi Yamagami, David J Seiffge, Davide Strambo, Peter A Ringleb, Robin Lemmens, Urs Fischer, Thanh N Nguyen, Johannes Kaesmacher

Faculty, Staff and Student Publications

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.

Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed …

Ras-Mutant Leukaemia Stem Cells Drive Clinical Resistance To Venetoclax, Junya Sango, Saul Carcamo, Maria Sirenko, Abhishek Maiti, Hager Mansour, Gulay Ulukaya, Lewis E Tomalin, Nataly Cruz-Rodriguez, Tiansu Wang, Malgorzata Olszewska, Emmanuel Olivier, Manon Jaud, Bettina Nadorp, Benjamin Kroger, Feng Hu, Lewis Silverman, Stephen S Chung, Elvin Wagenblast, Ronan Chaligne, Ann-Kathrin Eisfeld, Deniz Demircioglu, Dan A Landau, Piro Lito, Elli Papaemmanuil, Courtney D Dinardo, Dan Hasson, Marina Konopleva, Eirini P Papapetrou

Faculty, Staff and Student Publications

Cancer driver mutations often show distinct temporal acquisition patterns, but the biological basis for this, if any, remains unknown. RAS mutations occur invariably late in the course of acute myeloid leukaemia, upon progression or relapsed/refractory disease1-6. Here, by using human leukaemogenesis models, we first show that RAS mutations are obligatory late events that need to succeed earlier cooperating mutations. We provide the mechanistic explanation for this in a requirement for mutant RAS to specifically transform committed progenitors of the myelomonocytic lineage (granulocyte-monocyte progenitors) harbouring previously acquired driver mutations, showing that advanced leukaemic clones can originate from a different cell type …

Psychophysical And Functional Outcomes In Chemotherapy-Induced Peripheral Neuropathy After Spinal Cord Stimulation: A Narrative Review And Case Series, Peter D Vu, Kathleen Erin Mcdonough, Patrick M Dougherty, Ryan S D'Souza, Saba Javed

Faculty, Staff and Student Publications

Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a complication that may occur after treatment with various anticancer drugs. In refractory CIPN cases, spinal cord stimulation (SCS) has garnered increased attention. The use of gait analysis and psychophysical quantitative sensory testing (QST) as an objective measurement of CIPN-related damage has burgeoned; however, these changes have not been reported for patients with CIPN after SCS implantation using either burst or tonic stimulation.

Materials and methods: This manuscript encompasses two parts: 1) a presentation of pain improvement in a series of patients who underwent tonic vs burst SCS for CIPN measured by gait and …