Genetic Phenomena Commons^™

Early Mortality In Acute Myeloid Leukemia With Kmt2a Rearrangement Is Associated With High Risk Of Bleeding And Disseminated Intravascular Coagulation, Daniel Nguyen, Hagop M Kantarjian, Nicholas J Short, Wei Qiao, Jing Ning, Branko Cuglievan, Naval G Daver, Courtney D Dinardo, Elias J Jabbour, Tapan M Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Marina Y Konopleva, Michael Andreeff, Farhad Ravandi-Kashani, Koji Sasaki, Ghayas C Issa

Faculty, Staff and Student Publications

Background: Acute myeloid leukemia (AML) with rearrangement of lysine methyltransferase 2a gene (KMT2Ar) is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity.

Methods: In a retrospective analysis, causes and rates of early mortality following induction treatment were compared between a cohort of adults with KMT2Ar AML (N = 172) and an age-matched cohort of patients with normal karyotype AML (N = 522).

Results: The 60-day mortality in patients with KMT2Ar AML was 15% compared with 7% with normal karyotype (p = .04). We …

Eganelisib, A First-In-Class Pi3kγ Inhibitor, In Patients With Advanced Solid Tumors: Results Of The Phase 1/1b Mario-1 Trial, David S Hong, Michael Postow, Bartosz Chmielowski, Ryan Sullivan, Amita Patnaik, Ezra E W Cohen, Geoffrey Shapiro, Conor Steuer, Martin Gutierrez, Heather Yeckes-Rodin, Robert Ilaria, Brenda O'Connell, Joanna Peng, Guangbin Peng, Nora Zizlsperger, Anthony Tolcher, Jedd D Wolchok

Faculty, Staff and Student Publications

Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.

Patients and methods: Dose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE).

Results: …

Need For Risk Adjustment In Comparative Effectiveness And Cost-Effectiveness Studies In R/R Follicular Lymphoma, John Gribben, M Lia Palomba, Anik R Patel, Myrna Nahas, Sattva S Neelapu

Faculty, Staff and Student Publications

No abstract provided.

Asct Vs Cart For Patients With Relapsed Lbcl In Pr: Role Of Tmtv, Paolo Strati, Oren Pasvolsky, Lei Feng, Guofan Xu, Sanjit O Tewari, Jaimole Varghese, Karla Ow, Minifrida Santiago, Ajlan Al Zaki, Andrew Jallouk, Sattva S Neelapu, Partow Kebriaei, Elizabeth J Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

No abstract provided.

Leveraging Mid-Infrared Spectroscopic Imaging And Deep Learning For Tissue Subtype Classification In Ovarian Cancer, Chalapathi Charan Gajjela, Matthew Brun, Rupali Mankar, Sara Corvigno, Noah Kennedy, Yanping Zhong, Jinsong Liu, Anil K Sood, David Mayerich, Sebastian Berisha, Rohith Reddy

Faculty, Staff and Student Publications

Mid-infrared spectroscopic imaging (MIRSI) is an emerging class of label-free techniques being leveraged for digital histopathology. Modern histopathologic identification of ovarian cancer involves tissue staining followed by morphological pattern recognition. This process is time-consuming and subjective and requires extensive expertise. This paper presents the first label-free, quantitative, and automated histological recognition of ovarian tissue subtypes using a new MIRSI technique. This optical photothermal infrared (O-PTIR) imaging technique provides a 10× enhancement in spatial resolution relative to prior instruments. It enables sub-cellular spectroscopic investigation of tissue at biochemically important fingerprint wavelengths. We demonstrate that the enhanced resolution of sub-cellular features, combined …

Clinical Significance And Biology Of Circulating Tumor Dna In High-Risk Early-Stage Her2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy, Mark Jesus M Magbanua, Lamorna Brown Swigart, Ziad Ahmed, Rosalyn W Sayaman, Derrick Renner, Ekaterina Kalashnikova, Gillian L Hirst, Christina Yau, Denise M Wolf, Wen Li, Amy L Delson, Smita Asare, Minetta C Liu, Kathy Albain, A Jo Chien, Andres Forero-Torres, Claudine Isaacs, Rita Nanda, Debu Tripathy, Angel Rodriguez, Himanshu Sethi, Alexey Aleshin, Matthew Rabinowitz, Jane Perlmutter, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J Esserman, Angela M Demichele, Hope S Rugo, Laura J Van 'T Veer

Faculty, Staff and Student Publications

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival …

Prediction Of Disease Progression To Upfront Pembrolizumab Monotherapy In Advanced Non-Small-Cell Lung Cancer With High Pd-L1 Expression Using Baseline Ct Disease Quantification And Smoking Pack Years, Ali Silver, Cheryl Ho, Qian Ye, Jianjun Zhang, Ian Janzen, Jessica Li, Montgomery Martin, Lang Wu, Ying Wang, Stephen Lam, Calum Macaulay, Barbara Melosky, Ren Yuan

Faculty, Staff and Student Publications

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up …

Targeting Cxcr4 Abrogates Resistance To Trastuzumab By Blocking Cell Cycle Progression And Synergizes With Docetaxel In Breast Cancer Treatment, Shuying Liu, Shelly M Xie, Wenbin Liu, Mihai Gagea, Ariella B Hanker, Nguyen Nguyen, Akshara Singareeka Raghavendra, Gloria Yang-Kolodji, Fuliang Chu, Sattva S Neelapu, Adriano Marchese, Samir Hanash, Johann Zimmermann, Carlos L Arteaga, Debasish Tripathy

Faculty, Staff and Student Publications

Background: Although trastuzumab and other HER2-targeted therapies have significantly improved survival in patients with HER2 overexpressed or amplified (HER2+) breast cancer, a significant proportion of patients do not respond or eventually develop clinical resistance. Strategies to reverse trastuzumab resistance remain a high clinical priority. We were the first to report the role of CXCR4 in trastuzumab resistance. The present study aims to explore the therapeutic potential of targeting CXCR4 and better understand the associated mechanisms.

Methods: Immunofluorescent staining, confocal microscopy analysis, and immunoblotting were used to analyze CXCR4 expression. BrdU incorporation assays and flow cytometry were used to analyze dynamic …

Tubectomy With Delayed Oophorectomy As An Alternative To Risk-Reducing Salpingo-Oophorectomy In High-Risk Women To Assess The Safety Of Prevention: The Tuba-Wisp Ii Study Protocol, Miranda P Steenbeek, Majke H D Van Bommel, Joanna Inthout, Christine B Peterson, Michiel Simons, Kit C B Roes, Marleen Kets, Barbara M Norquist, Elizabeth M Swisher, Rosella P M G Hermens, Tuba-Wisp Ii Consortium, Karen H Lu, Joanne A De Hullu

Faculty, Staff and Student Publications

Background: Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.

Primary objective: To investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk.

Study hypothesis: We hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40-45 (BRCA1) …

A Global Catalog Of Whole-Genome Diversity From 233 Primate Species\, Lukas F K Kuderna, Hong Gao, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rousselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idrissa S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet

Faculty, Staff and Students Publications

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families …

Rare Penetrant Mutations Confer Severe Risk Of Common Diseases, Petko P Fiziev, Jeremy Mcrae, Jacob C Ulirsch, Jacqueline S Dron, Tobias Hamp, Yanshen Yang, Pierrick Wainschtein, Zijian Ni, Joshua G Schraiber, Hong Gao, Dylan Cable, Yair Field, Francois Aguet, Marc Fasnacht, Ahmed Metwally, Jeffrey Rogers, Tomas Marques-Bonet, Heidi L Rehm, Anne O'Donnell-Luria, Amit V Khera, Kyle Kai-How Farh

Faculty, Staff and Students Publications

We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ~10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared …

Phylogenomic Analyses Provide Insights Into Primate Evolution, Yong Shao, Long Zhou, Fang Li, Lan Zhao, Bao-Lin Zhang, Feng Shao, Jia-Wei Chen, Chun-Yan Chen, Xupeng Bi, Xiao-Lin Zhuang, Hong-Liang Zhu, Jiang Hu, Zongyi Sun, Xin Li, Depeng Wang, Iker Rivas-González, Sheng Wang, Yun-Mei Wang, Wu Chen, Gang Li, Hui-Meng Lu, Yang Liu, Lukas F K Kuderna, Kyle Kai-How Farh, Peng-Fei Fan, Li Yu, Ming Li, Zhi-Jin Liu, George P Tiley, Anne D Yoder, Christian Roos, Takashi Hayakawa, Tomas Marques-Bonet, Jeffrey Rogers, Peter D Stenson, David N Cooper, Mikkel Heide Schierup, Yong-Gang Yao, Ya-Ping Zhang, Wen Wang, Xiao-Guang Qi, Guojie Zhang, Dong-Dong Wu

Faculty, Staff and Students Publications

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our …

Coffee Intake, Caffeine Metabolism Genotype, And Survival Among Men With Prostate Cancer, Justin R Gregg, Jeri Kim, Christopher Logothetis, Sam Hanash, Xiaotao Zhang, Ganiraju Manyam, Kenneth Muir, Graham G Giles, Janet L Stanford, Sonja I Berndt, Manolis Kogevinas, Hermann Brenner, Rosalind A Eeles, Practical Consortium, Peng Wei, Carrie R Daniel

Faculty, Staff and Student Publications

Background: Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized.

Objective: To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer.

Design, setting, and participants: Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163C>A rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and >6 mo of follow-up.

Outcome measurements and statistical analysis: Multivariable-adjusted Cox …

De Novo Variants In Mrtfb Have Gain-Of-Function Activity In Drosophila And Are Associated With A Novel Neurodevelopmental Phenotype With Dysmorphic Features, Jonathan C Andrews, Jung-Wan Mok, Oguz Kanca, Sharayu Jangam, Cynthia Tifft, Ellen F Macnamara, Bianca E Russell, Lee-Kai Wang, Undiagnosed Diseases Network, Stanley F Nelson, Hugo J Bellen, Shinya Yamamoto, May Christine V Malicdan, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Purpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.

Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.

Results: Here, we report 2 pediatric probands with de novo …

Implication Of Chromosomal Microarray Analysis Prior To In-Utero Repair Of Fetal Open Neural Tube Defect, R Zemet, E Krispin, R M Johnson, N R Kumar, L E Westerfield, S Stover, D G Mann, J Castillo, H A Castillo, A A Nassr, M Sanz Cortes, R Donepudi, J Espinoza, W E Whitehead, M A Belfort, A A Shamshirsaz, I B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Objective: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair.

Methods: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at …

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Causal Linkage Of Presence Of Mutant Npm1 To Efficacy Of Novel Therapeutic Agents Against Aml Cells With Mutant Npm1, Christopher P Mill, Warren Fiskus, Kaberi Das, John A Davis, Christine E Birdwell, Tapan M Kadia, Courtney D Dinardo, Naval Daver, Koichi Takahashi, Koji Sasaki, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

In AML with NPM1 mutation causing cytoplasmic dislocation of NPM1, treatments with Menin inhibitor (MI) and standard AML chemotherapy yield complete remissions. However, the causal and mechanistic linkage of mtNPM1 to the efficacy of these agents has not been definitively established. Utilizing CRISPR-Cas9 editing to knockout (KO) or knock-in a copy of mtNPM1 in AML cells, present studies demonstrate that KO of mtNPM1 from AML cells abrogates sensitivity to MI, selinexor (exportin-1 inhibitor), and cytarabine. Conversely, the knock-in of a copy of mtNPM1 markedly sensitized AML cells to treatment with MI or cytarabine. Following AML therapy, most elderly patients with …

National Institutes Of Health Diversity Supplement Awards: Experience Of Radiation Oncology Principal Investigators And Trainees, Afua A Yorke, Michael K Rooney, Jillian Rigert, Amy C Moreno, Clifton D Fuller, Eric C Ford

Faculty, Staff and Student Publications

No abstract provided.

Adaptive Immunity In Genitourinary Cancers, Madhuri Koti, Trinity Bivalacqua, Peter C Black, Toni Cathomen, Matthew D Galsky, James L Gulley, Molly A Ingersoll, Ashish M Kamat, Wassim Kassouf, D Robert Siemens, Jianjun Gao

Faculty, Staff and Student Publications

Context: While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.

Objective: To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.

Evidence acquisition: We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators …

Cest-Mri For Body Oncologic Imaging: Are We There Yet?, Elena Vinogradov, Jochen Keupp, Ivan E Dimitrov, Stephen Seiler, Ivan Pedrosa

Faculty, Staff and Student Publications

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address …

2021 Aapm Equity, Diversity, And Inclusion Climate Survey Executive Summary, Kristi R G Hendrickson, Stephen M Avery, Richard Castillo, Laura Cervino, Ashley Cetnar, Nolan L Gagne, Wendy Harris, Amirh Johnson, Megan E Lipford, Nadia Octave, Kelly C Paradis, Angélica Pérez-Andújar, Surendra Prajapati, Julianne Pollard-Larkin

Faculty, Staff and Student Publications

Purpose: The American Association of Physicists in Medicine (AAPM) shares the results, conclusions, and recommendations from the initial Equity, Diversity, and Inclusion Climate Survey conducted in 2021.

Methods and materials: The climate survey targeted medical physicists who are full members of the AAPM and included demographic inquiries and questions intended to assess the working environmental climate in terms of a sense of belonging and inclusion, experiences of discrimination and harassment, and obstacles to participation within the AAPM. The survey invitation was sent to 5,500 members. Responses were collected from 1385 members (response rate of 25%) between January and February 2021. …

Author Correction: Pan-Cancer Analysis Of Whole Genomes Identifies Driver Rearrangements Promoted By Line-1 Retrotransposition, Bernardo Rodriguez-Martin, Eva G Alvarez, Adrian Baez-Ortega, Jorge Zamora, Fran Supek, Jonas Demeulemeester, Martin Santamarina, Young Seok Ju, Javier Temes, Daniel Garcia-Souto, Harald Detering, Yilong Li, Jorge Rodriguez-Castro, Ana Dueso-Barroso, Alicia L Bruzos, Stefan C Dentro, Miguel G Blanco, Gianmarco Contino, Daniel Ardeljan, Marta Tojo, Nicola D Roberts, Sonia Zumalave, Paul A Edwards, Joachim Weischenfeldt, Montserrat Puiggròs, Zechen Chong, Ken Chen, Eunjung Alice Lee, Jeremiah A Wala, Keiran M Raine, Adam Butler, Sebastian M Waszak, Fabio C P Navarro, Steven E Schumacher, Jean Monlong, Francesco Maura, Niccolo Bolli, Guillaume Bourque, Mark Gerstein, Peter J Park, David C Wedge, Rameen Beroukhim, David Torrents, Jan O Korbel, Iñigo Martincorena, Rebecca C Fitzgerald, Peter Van Loo, Haig H Kazazian, Kathleen H Burns, Cawg Structural Variation Working Group, Peter J Campbell, Jose M C Tubio, Pcawg Consortium

Faculty, Staff and Student Publications

No abstract provided.

Five-Year Overall Survival With Ipilimumab And Stereotactic Ablative Radiotherapy For Metastatic Disease, Kewen He, David S Hong, Chad Tang, Duygu Sezen, Livia Cox, Aurian Maleki, Genevieve Bertolet, Quynh-Nhu Nguyen, Nathan I Comeaux, Lily Schuda, Dawei Chen, James W Welsh

Faculty, Staff and Student Publications

Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900).

Methods and materials: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy …

Cumulative Burden Of Late, Major Surgical Intervention In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study (Ccss) Cohort, Bryan V Dieffenbach, Andrew J Murphy, Qi Liu, Duncan C Ramsey, Erik J Geiger, Lisa R Diller, Rebecca M Howell, Kevin C Oeffinger, Leslie L Robison, Yutaka Yasui, Gregory T Armstrong, Eric J Chow, Brent R Weil, Christopher B Weldon

Faculty, Staff and Student Publications

Background: Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions.

Methods: We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in …

Long-Term Outcomes Of Bevacizumab And Chemoradiation For Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial, Nancy Y Lee, Jonathan Harris, John Kim, Adam Garden, James Mechalakos, David G Pfister, Anthony T C Chan, Kenneth Hu, A Dimitrios Colevas, Steven Frank, George Shenouda, Voichita Bar-Ad, John N Waldron, Paul M Harari, Adam Raben, Pedro Torres-Saavedra, Quynh-Thu Le

Faculty, Staff and Student Publications

Importance: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Objective: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

Design, setting, and participants: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. …

Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Gynecologic Cancer, Mary L Disis, Sarah F Adams, Jyoti Bajpai, Marcus O Butler, Tyler Curiel, Shelley A Dodt, Laura Doherty, Leisha A Emens, Claire F Friedman, Margaret Gatti-Mays, Melissa A Geller, Amir Jazaeri, Veena S John, Katherine C Kurnit, John B Liao, Haider Mahdi, Anne Mills, Emese Zsiros, Kunle Odunsi

Faculty, Staff and Student Publications

Advanced gynecologic cancers have historically lacked effective treatment options. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration for the treatment of cervical cancer and endometrial cancer, offering durable responses for some patients. In addition, many immunotherapy strategies are under investigation for the treatment of earlier stages of disease or in other gynecologic cancers, such as ovarian cancer and rare gynecologic tumors. While the integration of ICIs into the standard of care has improved outcomes for patients, their use requires a nuanced understanding of biomarker testing, treatment selection, patient selection, response evaluation and surveillance, …

A Virtual Audit System For Intensity-Modulated Radiation Therapy Credentialing In Japan Clinical Oncology Group Clinical Trials: A Pilot Study, Mitsuhiro Nakamura, Dejun Zhou, Toshiyuki Minemura, Satoshi Kito, Hiroyuki Okamoto, Naoki Tohyama, Masahiko Kurooka, Yu Kumazaki, Masayori Ishikawa, Catharine H Clark, Elizabeth Miles, Joerg Lehmann, Nicolaus Andratschke, Stephen Kry, Satoshi Ishikura, Takashi Mizowaki, Teiji Nishio

Faculty, Staff and Student Publications

Purpose: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data.

Methods: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 …

Learning Through Doing: Comprehensive Programming For A Training Program In Cancer Disparities, Kayce D Solari Williams, Kamisha Hamilton Escoto, Crystal Roberson, Kathy Le, Lorraine R Reitzel, Lorna H Mcneill, Shine Chang

Faculty, Staff and Student Publications

In the United States, preparing researchers and practitioners for careers in cancer requires multiple components for success. In this reflection article, we discuss our approach to designing a comprehensive research training program in cancer disparities. We focused on elements that provide students and early career scientists a deep understanding of disparities through first-hand experiences and skills training necessary to build a research career in the area. Our Educational Program sits within the framework of an NCI P20 program, "UHAND (University of Houston/MD Anderson Cancer Center)", jointly established by an NCI-designated comprehensive cancer center and a minority-serving university as a collaborative …

The Effect Of Integrating Knowledge-Based Planning With Multicriteria Optimization In Treatment Planning For Prostate Sbrt, Sandun Jayarathna, Xinglei Shen, Ronald C Chen, H Harold Li, Kenny Guida

Faculty, Staff and Student Publications

Knowledge-based planning (KBP) and multicriteria optimization (MCO) are two powerful tools to assist treatment planners in achieving optimal target coverage and organ-at-risk (OAR) sparing. The purpose of this work is to investigate if integrating MCO with conventional KBP can further improve treatment plan quality for prostate cancer stereotactic body radiation therapy (SBRT). A two-phase study was designed to investigate the impact of MCO and KBP in prostate SBRT treatment planning. The first phase involved the creation of a KBP model based on thirty clinical SBRT plans, generated by manual optimization (KBP_M). A ten-patient validation cohort was used to compare manual, …

Flt3 Inhibitors Upregulate Cxcr4 And E-Selectin Ligands Via Erk Suppression In Aml Cells And Cxcr4/E-Selectin Inhibition Enhances Anti-Leukemia Efficacy Of Flt3-Targeted Therapy In Aml, Yannan Jia, Weiguo Zhang, Mahesh Basyal, Kyung Hee Chang, Lauren Ostermann, Jared K Burks, Charlie Ly, Hong Mu-Mosley, Qi Zhang, Xin Han, William E Fogler, John L Magnani, Arnaud Lesegretain, Anna A Zal, Tomasz Zal, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.