Medical Specialties Commons^™

Toward Online Adaptive Proton Therapy Of Sinonasal Cancer: The Dosimetric Accuracy Of Utilizing Deep-Learning Synthetic Ct From Cbct For Daily Treatment Dose Verification, An Qin, Lewei Zhao, Shupeng Chen, Xiaoqiang Li, Weili Zheng, Di Yan, Rohan Deraniyagala, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Investigate The Delivery Efficiency And Accuracy Of Spot-Scanning Proton Arc (Sparc) In Comparison With Conventional Impt, Automatic Step-And-Shoot Multifield Impt, Lewei Zhao, Gang Liu, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations and Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Whole-Exome Sequencing Identifies Somatic Mutations And Intratumor Heterogeneity In Inflammatory Breast Cancer., Rui Luo, Weelic Chong, Qiang Wei, Zhenchao Zhang, Chun Wang, Zhong Ye, Maysa Abu-Khalaf, Daniel P. Silver, Robert T. Stapp, Wei Jiang, Ronald E. Myers, Bingshan Li, Massimo Cristofanilli, Hushan Yang

Department of Medical Oncology Faculty Papers

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, …

Assess The Interplay Effect Based On The Cyclotron Accelerator Proton Therapy System Machine-Specific Delivery Sequence Model, Lewei Zhao, Gang Liu, J Shen, A Lee, Di Yan, Rohan Deraniyagala, Craig Stevens, Weili Zheng, Xiaoqiang Li, S Tang, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Spermatocytic Tumor Of Testis In A Young Male, Madiha Bilal Qureshi, Nasir Ud Din, Zubair Ahmad, Saira Fatima

Department of Pathology and Laboratory Medicine

Spermatocytic tumor is a rare germ cell tumor not related to germ cell neoplasia in situ, and derived from postpubertal-type germ cells. It was previously called "Spermatocytic Seminoma" due to false belief of its origin from germ cell neoplasia in situ. The tumor usually occurs in an older age group and orchidectomy is curative. We present a case of spermatocytic tumor in a 25-year male who presented with right-sided testicular swelling and right-sided varicocele. Radiology revealed a 9.8 × 9 cm testicular mass and the patient underwent right-sided orchidectomy. Microscopic examination showed classic morphology with three characteristic cell types and …

The Synergy Of Bet Inhibitors With Aurora A Kinase Inhibitors In Mycn-Amplified Neuroblastoma Is Heightened With Functional Tp53, Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson

Faculty, Staff and Students Publications

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared …

Prevalence Of Tp-53/Rb-1 Co-Mutation In Large Cell Neuroendocrine Carcinoma, Hoda Saghaeiannejad Esfahani, Cory M. Vela, Aman Chauhan

Internal Medicine Faculty Publications

Introduction: Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive high-grade neuroendocrine neoplasm, which can arise from anywhere in the body. Due to its rarity there is a lacuna in our understanding of LCNEC’s molecular biology. In 2016, Rekhtman and colleagues presented one of the largest molecular sequencing series of pulmonary LCNEC. They differentiated genomic profiles of LCNEC into two major subsets: small cell lung cancer (SCLC)-like, characterized by TP53 + RB1 co-mutation/loss, and non-small cell lung cancer (NSCLC)-like, characterized by the lack of co-altered TP53 + RB1. This finding is of significance because at present LCNEC patients …

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 …

Dexrazoxane Decreases The Cardiotoxic Effects Of Doxorubicin In Osteosarcoma Patients Without Increasing Mortality From Secondary Malignant Neoplasms, Thomas S. Przybycien

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Schwartz CL, Wexler LH, Krailo MD, et al. Intensified chemotherapy with dexrazoxane cardioprotection in newly diagnosed nonmetastatic osteosarcoma: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2016;63(1):54-615. https://doi.org/10.1002/pbc.25753

for a patient with osteosarcoma and concerns about the risk of secondary malignant neoplasms that attend use of dexarazoxane.

Team-Based Outreach To Improve Colorectal Cancer Screening Rates In An Urban Family Medicine Practice, Alexa Waters, Md, Olivia Seecof, Md, Graham Stratton, Md, Caitlyn Haines, Md, Brittany Hozick, Md, Jose Medina, Md, Kathryn Topalis, Md, Hannah Facey, Md, Chelsea Salas-Tam, Md, David Peters, Md

Health Equity and Quality Improvement (HEQI) Summit

Aims for Improvement

• Aim to increase CRCS rates for our resident team patients by 5% by May, 2021
• Target Population (n=99): Age 50-74, due for CRCS, office visit within last 2 years, team resident listed as PCP, active on MyChart, and speak English

Adolescent And Young Adult Oncology Patient And Provider Perspectives In Philadelphia (Aya-4p), Christoher Terry, Md, Miriam Pomerantz, Lsw, Jodi Sandos, Lcsw, Lindsay Wilde, Md

Health Equity and Quality Improvement (HEQI) Summit

Primary Objectives

• To assess the current perspective of AYA patients regarding medical services and psychosocial support delivered to AYAs in Philadelphia
• To assess the current knowledge and perspective of healthcare providers at the SKCC about the care and services needed by AYA patients

Increasing The Rate Of Excisional Lymph Node Biopsies At Easily Accessible Sites When Ruling Out Lymphoma, Catherine M. Tucker, Md, Xiangyun Ye, Christopher Gardner, Austin Redilla, Guldeep K. Uppal, Md, Adam F. Binder, Md

Health Equity and Quality Improvement (HEQI) Summit

The aim of this study is to increase the rate of excisional lymph node biopsies from 78% to 95% in patients presenting to the Center City campus with lymphadenopathy at easily accessible sites by September 2021.

Preparing Historically Underrepresented Trainees For Biomedical Cancer Research Careers At Huntsman Cancer Institute/University Of Utah Health., Ana Maria Lopez, Md, Mph, Macp, José E Rodríguez, Kathryn Browning Hawes, Anna Marsden, Don Ayer, Donna Harp Ziegenfuss, Kola Okuyemi

Department of Medical Oncology Faculty Papers

Given the well-documented inequities in health care outcomes by race, ethnicity, and gender, many health career pipeline programs have focused on supporting the development of a diverse and inclusive workforce. The State of Utah, is vast, but sparsely populated outside the Salt Lake City metropolitan area. More than 96% of our nearly 85,000 square miles is designated rural (<100 people/square mile) or frontier (<7 people/square mile). The Salt Lake City area is home to the Hunsman Cancer Institute, the only NCI-designated Comprehensive Cancer Center in the region, also noted the limited diversity in the biomedical cancer research workforce. Our primary objective was to increase the number of underrepresented trainees who pursue higher education with the goal of a career in cancer research. PathMaker is a regional, competitive pipeline program that nurtures high school or undergraduate trainees from historically underrepresented backgrounds towards a career in cancer research. Our faculty and staff team collaboratively developed a cohort model curriculum that increased student awareness of research …

Exploring The Therapeutic Relationship As A Central Focus Through Expressive Arts Therapy In Oncology, Akshata Parekh

Expressive Therapies Capstone Theses

The treatment for cancer can be physically, mentally, emotionally and socially challenging. These treatments have side effects like physical body pain, hair loss, changes in weight, energy, nausea and more. These physical changes impact the social, mental and emotional well-being of the patient and makes this journey of the life-threating prognosis of cancer very tough to confront. Expressive arts therapy provides a safe space for the patients to address their mental health concerns as a result of this treatment. The Capstone Thesis Project explored expressive arts therapy interventions with 95 patients through single or multiple sessions while going through their …

Deep Learning Predicts Chromosomal Instability From Histopathology Images, Zhuoran Xu, Akanksha Verma, Uska Naveed, Samuel F. Bakhoum, Pegah Khosravi, Olivier Elemento

Publications and Research

Chromosomal instability (CIN) is a hallmark of human cancer yet not readily testable for patients with cancer in routine clinical setting. In this study, we sought to explore whether CIN status can be predicted using ubiquitously available hematoxylin and eosin histology through a deep learning-based model. When applied to a cohort of 1,010 patients with breast cancer (Training set: n = 858, Test set: n = 152) from The Cancer Genome Atlas where 485 patients have high CIN status, our model accurately classified CIN status, achieving an area under the curve of 0.822 with 81.2% sensitivity and 68.7% specificity in …

Emerging Role Of Fascin-1 In The Pathogenesis, Diagnosis, And Treatment Of The Gastrointestinal Cancers., Bojana Ristic, Jonathan Kopel, Syed A A Sherazi, Shweta Gupta, Sonali Sachdeva, Pardeep Bansal, Aman Ali, Abhilash Perisetti Md, Hemant Goyal

PCI Publications and Projects

Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. Invasion of primary cancer occurs by the actin cytoskeleton remodeling, including the formation of the filopodia, stereocilia, and other finger-like membrane protrusions. The crucial step of actin remodeling in the malignant cells is mediated by the fascin protein family, with fascin-1 being the most active. Fascin-1 is an actin-binding protein that cross-links filamentous actin into tightly packed parallel bundles, giving rise to finger-like cell protrusions, thus equipping the …

Can An Amino Acid Mixture Alleviate Gastrointestinal Symptoms In Neuroendocrine Tumor Patients?, Aman Chauhan, Satya Das, Rachel Miller, Laura Luque, Samuel N. Cheuvront, James Cloud, Zach Tarter, Fariha Siddiqui, Robert A. Ramirez, Lowell B. Anthony

Internal Medicine Faculty Publications

Background: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models.

Methods: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval.

Results: Ninety-eight NET patients who …

Pi3k/Mtor Dual Inhibitor Pf-04691502 Is A Schedule-Dependent Radiosensitizer For Gastroenteropancreatic Neuroendocrine Tumors, Zeta Chow, Jeremy Johnson, Aman Chauhan, Tadahide Izumi, Michael Cavnar, Heidi L. Weiss, Courtney M. Townsend Jr., Lowell B. Anthony, Carrigan Wasilchenko, Matthew L. Melton, Jörg Schrader, B. Mark Evers, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up …

Mircorrnet: Machine Learning-Based Integration Of Mirna And Mrna Expression Profiles, Combined With Feature Grouping And Ranking., Malik Yousef, Gokhan Goy, Ramkrishna Mitra, Christine M. Eischen, Amhar Jabeer, Burcu Bakir-Gungor

Department of Cancer Biology Faculty Papers

A better understanding of disease development and progression mechanisms at the molecular level is critical both for the diagnosis of a disease and for the development of therapeutic approaches. The advancements in high throughput technologies allowed to generate mRNA and microRNA (miRNA) expression profiles; and the integrative analysis of these profiles allowed to uncover the functional effects of RNA expression in complex diseases, such as cancer. Several researches attempt to integrate miRNA and mRNA expression profiles using statistical methods such as Pearson correlation, and then combine it with enrichment analysis. In this study, we developed a novel tool called miRcorrNet, …

Development Of A Multilevel Intervention To Increase Colorectal Cancer Screening In Appalachia, Aaron J Kruse-Diehr, Jill M Oliveri, Robin C Vanderpool, Mira L Katz, Paul L Reiter, Darrell M Gray, Michael L Pennell, Gregory S Young, Bin Huang, Darla Fickle, Mark Cromo, Melinda Rogers, David Gross, Ashley Gibson, Jeanne Jellison, Michael D Sarap, Tonia A Bivens, Tracy D Mcguire, Ann Scheck Mcalearney, Timothy R Huerta, Saurabh Rahurkar, Electra D Paskett, Mark Dignan

Faculty, Staff and Student Publications

BACKGROUND: Colorectal cancer (CRC) screening rates are lower in Appalachian regions of the United States than in non-Appalachian regions. Given the availability of various screening modalities, there is critical need for culturally relevant interventions addressing multiple socioecological levels to reduce the regional CRC burden. In this report, we describe the development and baseline findings from year 1 of "Accelerating Colorectal Cancer Screening through Implementation Science (ACCSIS) in Appalachia," a 5-year, National Cancer Institute Cancer Moonshot

METHODS: Project development was theory-driven and included the establishment of both an external Scientific Advisory Board and a Community Advisory Board to provide guidance in …

Efficacy Of Half-Day Workshops For Internal Medicine Interns In Educating Breaking-Bad-News Discussions, Colin Thomas, Christine Kurian, Sarah Houtmann, Neil D. Palmisiano

Division of Internal Medicine Faculty Papers & Presentations

Background: Adequate end-of-life (EOL) care/breaking-bad-news (BBN) discussions with patients are becoming increasingly essential to adequate patient care. Purpose: Whether a half-day workshop would lead to improved confidence in EOL/BBN care discussions for internal medicine interns. Methods: Internal medicine interns (n = 43) were assigned to participate in a half-day workshop at Thomas Jefferson University Hospital. The workshop involved two standardized patient (SP) interactions involving delivering news of a terminal illness/initiating goals of care discussion with the intervention of SP feedback, a didactic and lecture on proper EOL/BBN discussion. Voluntary anonymous surveys before and after the workshop were utilized to …

Magnetic Resonance-Guided High Intensity Focused Ultrasound (Mrghifu) Induced Hyperthermia (Ht) For Treatment Of Cervical Cancer, Lifei Zhu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hyperthermia (HT), which refers to increasing the temperature of the tumor tissue to 40–45°C for an extended period of time, has been reported to be one of the most effective sensitizers for radiation therapy (RT) and/or chemotherapy. High intensity focused ultrasound (HIFU) has been developed as a non-invasive and non-ionizing tool to induce localized HT. Magnetic resonance thermometry (MR thermometry) is one of the most reliable methods for non-invasively and precisely measuring the in vivo volumetric temperature in real time. The integration of MR thermometry with HIFU has been implemented in commercially available magnetic resonance guided high intensity focused ultrasound …

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

Levofloxacin Versus Ciprofloxacin Prophylaxis In Pediatric Cancer Patients At High Risk Of Infection, Chandni Dargan Md, Amy Johnson Md, Mba

Research Days

Background: Patients with cancer and those undergoing chemotherapy are at risk of developing bacterial infections due to myelosuppression. Patients undergoing the most intensive chemotherapy regimens are at a higher risk for morbidity and mortality due to profound neutropenia. Antibacterial prophylaxis is given to reduce the incidence of infection in those at highest risk. Starting March 1, 2016 our institution used ciprofloxacin for antibacterial prophylaxis however recent literature, including the COG trial ACCL0934, supports using levofloxacin in certain high risk (HR) populations due to greater efficacy in reducing neutropenic fever (NF) and bacteremia. Therefore, we switched to this April 1, 2019. …

A Pediatric Case Of Treatment-Related Myelodysplastic Syndrome While On Therapy For Pre-B All, Sara Mcelroy

Research Days

Background: Treatment-related myelodysplastic syndrome (t-MDS) is a known, but rare, late effect of cancer therapy, specifically radiation, alkylating agents or topoisomerase II inhibitors. When secondary to treatment with alkylating agents, t-MDS typically occurs 4 to 7 years after therapy, and common cytogenetics include chromosomes 5 and 7 abnormalities. Treatment in children with t-MDS is typically allogeneic stem cell transplant, but the prognosis remains poor.

Objectives/Goal: To describe a rare case of a pediatric patient who developed t-MDS while receiving treatment for Pre-B Cell Acute Lymphoblastic Leukemia (pre-B ALL) and to outline the treatment regimen that he received.

Methods/Design: Case Report …

Changes In Family Functioning During The First Year Of Pediatric Cancer Treatment: A Mixed-Method Pilot Study, Carolyn Bates

Research Days

Background: A new diagnosis of pediatric cancer presents a sudden and tremendous stressor for families of all backgrounds and circumstances (Long & Marsland, 2011; Bemis et al., 2015). Although many families are resilient in the context of new cancer diagnosis, approximately 33% are at risk for negative outcomes due to psychosocial distress and difficulties with effective coping (Kazak et al., 2020; Pai et al., 2008), supporting the need for systematic assessment of psychosocial health as a standard of care in pediatric oncology (Kazak et al., 2015). Alongside heightened stress within the first year of diagnosis, parents may relax family rules …

Impact Of Covid-19 On Families With A Child In Cancer Treatment, Mirae J. Fornander

Research Days

Background: A new diagnosis of pediatric cancer diagnosis is a sudden and tremendous stressor to families (Long & Marsland, 2011). The COVID-19 pandemic presented an acute, universal stressor that impacted daily life around the world (Brooks et al., 2020). The impact of the COVID-19 pandemic on children with cancer and their families is not yet known.

Objectives/Goal: The current study is a pilot investigation of COVID-19 exposure and impact among a sample of families with a child being treated for cancer.

Methods/Design: Primary caregivers (N=22) of a child (M age=7.4, SD=4.6) who was diagnosed with cancer within the last 18 …

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells …

Survival Following Relapse In Children With Acute Myeloid Leukemia: A Report From Aml-Bfm And Cog., Mareike Rasche, Martin Zimmermann, Emma Steidel, Todd Alonzo, Richard Aplenc, Jean-Pierre Bourquin, Heidrun Boztug, Todd Cooper, A S. Gamis, Robert B. Gerbing, Iveta Janotova, Jan-Henning Klusmann, Thomas Lehrnbecher, Nora Mühlegger, Nils V. Neuhoff, Naghmeh Niktoreh, Lucie Sramkova, Jan Stary, Katharina Waack, Christiane Walter, Ursula Creutzig, Michael Dworzak, Gertjan Kaspers, Edward Anders Kolb, Dirk Reinhardt

Manuscripts, Articles, Book Chapters and Other Papers

Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM …