Medical Specialties Commons^™

Durable Remission After Targeted Therapy In Braf V600e–Mutant Metastatic Colorectal Cancer: Case Report, Daniel A Fox, Deepak Bhamidipati, Scott Kopetz, David S Hong

Faculty, Staff and Student Publications

BRAF mutation leads to constitutive activation of the MAPK pathway and is associated with the immune-activating molecular subtype of colorectal cancer. Targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (CRC) has significantly improved outcomes for these patients when combined with anti–epithelial growth factor receptor (EGFR) therapy. However, most patients ultimately develop disease progression. We report a case of a patient with metastatic-deficient mismatch repair, BRAF V600E–mutated CRC, who achieved a durable complete response to vemurafenib plus cetuximab and chemotherapy despite initial high burden of disease, including peritoneal involvement. Recent clinical trials of combined anti-EGFR/anti–BRAF V600E therapy in …

A Phase Ib Trial Of Selinexor In Combination With Immune Checkpoint Blockade In Patients With Advanced Renal Cell Carcinoma, Omar Alhalabi, Mohamed A Gouda, Denái R Milton, Hassan Ahmed Momin, Bulent Yilmaz, Bettzy Stephen, Chinenye Lynette Ejezie, Justin Tyler Moyers, Serdar A Gurses, Jeffrey How, Siqing Fu, Jordi Rodon, David S Hong, Sarina A Piha-Paul, Vivek Subbiah, Ecaterina Elena Dumbrava, Daniel D Karp, Filip Janku, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.

Methods: NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL + NIVO and SEL …

Hsp90: Bringing It All Together, Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Faculty, Staff and Student Publications

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs most other machines in the cell in sophistication. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …

Best Practices For Delivering Neoadjuvant Therapy In Pancreatic Ductal Adenocarcinoma, Jordan M Cloyd, Angela Sarna, Matthew J Arango, Susan E Bates, Manoop S Bhutani, Mark Bloomston, Vincent Chung, Efrat Dotan, Cristina R Ferrone, Patricia F Gambino, Ajit H Goenka, Karyn A Goodman, William A Hall, Jin He, Melissa E Hogg, Shiva Jayaraman, Avinash Kambadakone, Matthew H G Katz, Alok A Khorana, Andrew H Ko, Eugene J Koay, David A Kooby, Somashekar G Krishna, Liliana K Larsson, Richard T Lee, Anirban Maitra, Nader N Massarweh, Sameh Mikhail, Mahvish Muzaffar, Eileen M O'Reilly, Manisha Palta, Maria Q B Petzel, Philip A Philip, Marsha Reyngold, Daniel Santa Mina, Davendra P S Sohal, Tilak K Sundaresan, Susan Tsai, Kea L Turner, Timothy J Vreeland, Steve Walston, M Kay Washington, Terence M Williams, Jennifer Y Wo, Rebecca A Snyder

Faculty, Staff and Student Publications

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Design, setting, and participants: This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature …

Molecular Classification Of Endometrial Cancers (Ec) And Association With Relapse-Free Survival (Rfs) And Overall Survival (Os) Outcomes: Ancillary Analysis Of Gog-0258, Aine Clements, Danielle Enserro, Kyle C Strickland, Rebecca Previs, Daniela Matei, David Mutch, Matthew Powell, Ann Klopp, David Scott Miller, William Small, Paul Disilvestro, Nick Spirtos, Casey Cosgrove, Greg Sfakianos, J Rebecca Liu, Roberto Vargas, Mark Shahin, Bradley Corr, Kimberly Dessources, Frederick Ueland, David Warshal, Jessica Gillen, Angeles Alvarez Secord

Faculty, Staff and Student Publications

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype.

Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had …

Undervaluing Nondrug Rewards Or Overvaluing Cocaine? Cocaine Demand Relates To Cocaine Use Severity More Strongly Than Anhedonia In Individuals With Cocaine Use Disorder, Cecilia Nunez, Jin H Yoon, Constanza De Dios, Vincent Dang, Scott D Lane, Jessica N Vincent, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of non-drug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The current study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial (SMART) aimed at developing adaptive interventions for CUD. We examined the …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Spontaneous Cervical And Mediastinal Hematoma Due To Rupture Of Inferior Thyroid Artery, Takayuki Yamada, Satoru Yanagaki, Nozomi Satani, Yuriko Kagaya, Tomoni Sato, Tomonori Matsuura, Teruyuki Sato, Naoya Noguchi, Nobuo Ohta

Faculty, Staff and Student Publications

A 62-year-old man was referred to our hospital presenting with a sore throat, dyspnea, and cervical swelling. Initial precontrast CT scans revealed a cervical and mediastinal hematoma, along with a hemothorax. Further dynamic contrast-enhanced CT scans indicated contrast media extravasation dorsal to the right thyroid gland lobe, suggesting a rupture of the right inferior thyroid artery or a parathyroid adenoma. Following endotracheal intubation, angiography confirmed extravasation from the right inferior thyroid artery. Transarterial embolization (TAE) was successfully performed using a gelatin sponge. The cervical and mediastinal hematoma were surgically excised, and the right inferior parathyroid gland was simultaneously resected. Pathological …

Advancing Diagnostic Accuracy And Quality Of Patient Care Through The Implementation Of A Flow Cytometry Quality Assurance Program, Dylan Wang, Hong Fang, Chi Young Ok, Jeffrey L Jorgensen, L Jeffrey Medeiros, Wei Wang, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification, and disease monitoring of hematologic neoplasms. The interpretation of flow cytometry testing can be challenging.

Objective.—: To explore ways to improve diagnostic accuracy and in turn enhance the quality of patient care.

Design.—: A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed. The outcomes of the QA review were categorized into 3 groups: complete agreement, minor discrepancy, and major discrepancy. Each discrepancy underwent a process of documentation, discussion, and resolution. Here we summarize our 3 …

Safety And Efficacy Of Toripalimab In Patients With Cholangiocarcinoma: An Open-Label, Phase 1 Study, Aung Naing, Amit Mahipal, Milind Javle, Judy Wang, Todd M Bauer, David L Bajor, Anthony D Elias, Anthony Shields, Elizabeth Davis, Sant Chawla, Howard Safran, John D Powderly, Gina D'Amato, Christian F Meyer, Xiongwen Tang, Sheng Yao, Patricia Keegan

Faculty, Staff and Student Publications

Introduction: This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.

Methods: Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B. The primary endpoint was safety assessment. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), …

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

A Multicenter Open-Label Randomized Phase Ii Study Of Osimertinib With And Without Ramucirumab In Tyrosine Kinase Inhibitor–Naïve Egfr-Mutant Metastatic Non–Small Cell Lung Cancer (Ramose Trial), Xiuning Le, Jyoti D Patel, Elaine Shum, Christina Baik, Rachel E Sanborn, Catherine A Shu, Chul Kim, Mary Jo Fidler, Richard Hall, Yasir Y Elamin, Janet Tu, George Blumenschein, Jianjun Zhang, Don Gibbons, Carl Gay, Nisha A Mohindra, Young Chae, Yanis Boumber, Joshua Sabari, Rafael Santana-Davila, Shane Rogosin, Benjamin Herzberg, Ben Creelan, Bruna Pellini, Tawee Tanvetyanon, Simon Heeke, Mike Hernandez, Jhanelle E Gray, Andreas Saltos, John V Heymach

Faculty, Staff and Student Publications

Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).

Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for …

Real-World Neoadjuvant And Adjuvant Trastuzumab-Containing Regimen Patterns And Their Association With Survival Among Patients With Operable Her2-Positive Breast Cancer From 2007 To 2021, Hui Zhao, Chan Shen, Jaime J Laureano, Xiudong Lei, Jiangong Niu, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Chemotherapy in combination with trastuzumab is the standard neoadjuvant and adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Assessing the regimens administered to patients with HER2-positive BC in the real world is lacking. We evaluated neoadjuvant and adjuvant regimen patterns among HER2-positive BC patients (2007 to 2021) identified in a health insurance claims database.

Methods: Female BC patients ≥ 18 years who received chemotherapy, surgery, and trastuzumab were chosen from Optum's de-identified Clinformatics® Data Mart database. Summary statistics, Joinpoint models, Kaplan-Meier survival curves, and Cox regression models were used to analyze the data.

Results: …

Pexidartinib And Standard Neoadjuvant Therapy In The Adaptively Randomized I-Spy2 Trial For Early Breast Cancer, Hope S Rugo, Mike Campbell, Christina Yau, A Jo Chien, Anne M Wallace, Claudine Isaacs, Judy C Boughey, Hyo S Han, Meredith Buxton, Julia L Clennell, Smita M Asare, Katherine Steeg, Amy Wilson, Ruby Singhrao, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Nola M Hylton, Angela M Demichele, Douglas Yee, Laura J Van't Veer, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.

Results: A total of 9 participants were randomized to receive pexidartinib …

Decoding Cancer Etiology With Cellular Reprogramming, Mo-Fan Huang, Megan E Fisher, Trinh T T Phan, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

Cancer research remains clinically unmet in many areas due to limited access to patient samples and the lack of reliable model systems that truly reflect human cancer biology. The emergence of patient-derived induced pluripotent stem cells and engineered human pluripotent stem cells (hPSCs) has helped overcome these challenges, offering a versatile alternative platform for advancing cancer research. These hPSCs are already proving to be valuable models for studying specific cancer driver mutations, offering insights into cancer origins, pathogenesis, tumor heterogeneity, clonal evolution, and facilitating drug discovery and testing. This article reviews recent progress in utilizing hPSCs for clinically relevant cancer …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Selinexor (Kpt-330) In Combination With Immune Checkpoint Inhibition In Uveal Melanoma: A Phase 1b Trial, Mohamed A Gouda, Abdulrazzak Zarifa, Yali Yang, Bettzy Stephen, Serdar A Gurses, Ashabari Sprenger, Yanyan Tian, Mohamed H Derbala, Isabella Glitza Oliva, Funda Meric-Bernstam, Sapna P Patel

Faculty, Staff and Student Publications

Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.

Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma. Patients received selinexor 60 mg PO twice weekly with standard of care, commercially available immune checkpoint inhibitor of the investigator's choice. In …

Imaging Lung Tumor Motion Using Integrated-Mode Proton Radiography-A Phantom Study Towards Tumor Tracking In Proton Radiotherapy, Ryan Fullarton, Mikaël Simard, Lennart Volz, Allison Toltz, Savanna Chung, Christoph Schuy, Daniel G Robertson, Gary Royle, Sam Beddar, Colin Baker, Christian Graeff, Charles-Antoine Collins-Fekete

Faculty, Staff and Student Publications

BACKGROUND: Motion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.

PURPOSE: Proton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated-mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring …

Rapidbrachyivbt: A Dosimetry Software For Patient-Specific Intravascular Brachytherapy Dose Calculations On Optical Coherence Tomography Images, Maryam Rahbaran, Jonathan Kalinowski, Joseph M Decunha, Kevin J Croce, Brian A Bergmark, James M G Tsui, Phillip M Devlin, Shirin A Enger

Faculty, Staff and Student Publications

Background: Coronary artery disease is the most common form of cardiovascular disease. It is caused by excess plaque along the arterial wall, blocking blood flow to the heart (stenosis). A percutaneous coronary intervention widens the arterial wall with the inflation of a balloon inside the lesion area and leaves behind a metal stent to prevent re-narrowing of the artery (restenosis). However, in-stent restenosis may occur due to damage to the arterial wall tissue, triggering neointimal hyperplasia, producing fibrotic and calcified plaques and narrowing the artery again. Drug-eluting stents, which slowly release medication to inhibit neointimal hyperplasia, are used to prevent …

Open-Chest Cardiac Ultrasound-Mediated Imaging With A Vacuum Coupler, Nilesh Mathuria, Krithik Vishwanath, Giorgio Brero, Blake C Fallon, Antonio Martino, Richard C Willson, Carly S Filgueira, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods.

PURPOSE: To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches.

METHODS: The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the …

Outcomes Of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants An Independent Prognostic Designation, Jayastu Senapati, Hagop M Kantarjian, Fadi G Haddad, Nicholas J Short, Gautam Borthakur, Rashmi Kanagal-Shamanna, Guilin Tang, Elias Jabbour, Courtney D Dinardo, Naval Daver, Guillermo Montalban-Bravo, Vishrut Shah, Amin Alousi, Elizabeth Shpall, Uday Popat, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Mutational And Co-Mutational Landscape Of Early Onset Colorectal Cancer, Jumanah Yousef Alshenaifi, Guglielmo Vetere, Giulia Maddalena, Mahmoud Yousef, Michael G White, John Paul Shen, Eduardo Vilar, Christine Parseghian, Arvind Dasari, Van Karlyle Morris, Ryan Huey, Michael J Overman, Robert Wolff, Kanwal P Raghav, Jason Willis, Kristin Alfaro, Andy Futreal, Y Nancy You, Scott Kopetz

Faculty, Staff and Student Publications

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations …

Rapid Whole Genome Sequencing Uncovers A Triple Diagnosis: X-Linked Chondrodysplasia Punctata, Mecp2-Related Disorder, And Mosaic Jacobs Syndrome, Megan Samuels, Kathleen Shields, Paul Hillman, Laura Farach

Faculty, Staff and Student Publications

Background: Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences.

Methods and results: This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2-related …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

Preclinical And Clinical-Scale Magnetic Particle Imaging Of Natural Killer Cells: In Vitro And Ex Vivo Demonstration Of Cellular Sensitivity, Resolution, And Quantification, Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) …

Toward A Biological Definition Of Neuronal And Glial Synucleinopathies, Claudio Soto, Brit Mollenhauer, Oskar Hansson, Un Jung Kang, Roy N Alcalay, David Standaert, Claudia Trenkwalder, Kenneth Marek, Douglas Galasko, Kathleen Poston

Faculty, Staff and Student Publications

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms. We underscore the utility of the αSyn seed amplification assay to detect aggregated αSyn in living …

Refining Diagnostic Subtypes Of Peripheral T-Cell Lymphoma Using A Multiparameter Approach, Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Ab Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) …

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …