Medical Specialties Commons^™

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 …

Receipt Of Home Health And 30-Day Outcomes Among Veterans With Dementia Following Inpatient Surgery, Heather Davila, Yubo Gao, Katherine E Hadlandsmyth, Andrea L Strayer, Michael A Jacobs, Robert A Tessler, Paula K Shireman, George L Wehby, Susanne Schmidt, Leslie R M Hausmann, Carly A Jacobs, Daniel E Hall, Mary Vaughan Sarrazin

Faculty, Staff and Student Publications

No abstract provided.

Assessment Of Racial Bias Within The Risk Analysis Index Of Frailty, Michael A Jacobs, Leslie R M Hausmann, Robert M Handzel, Susanne Schmidt, Carly A Jacobs, Daniel E Hall

Faculty, Staff and Student Publications

Objective: Our objective was to assess potential racial bias within the Risk Analysis Index (RAI).

Background: Patient risk measures are rarely tested for racial bias. Measures of frailty, like the RAI, need to be evaluated for poor predictive performance among Black patients.

Methods: Retrospective cohort study using April 2010-March 2019 Veterans Affairs Surgical Quality Improvement Program and 2010-2019 National Surgical Quality Improvement Program data. The performance of the RAI and several potential variants were compared between Black and White cases using various metrics to predict mortality (180-day for Veterans Affairs Surgical Quality Improvement Program, 30-day for National Surgical Quality Improvement …

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 …

Emergence Of Igh::Ccnd1 Rearrangement And Mutations In Tp53, Btk, And Bcl2 Associated With Therapy Resistance In Chronic Lymphocytic Leukemia, Qing Wei, Hong Fang, James M Jing, Roman Segura-Rivera, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is an indolent low-grade B-cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cell lymphoma. We report a case of CLL with the emergence of an IGH::CCND1 rearrangement and mutations associated with treatment resistance, including TP53, BTK, and BCL2, during disease progression. Immunophenotypic, cytogenetic, and molecular analyses support that these alterations are secondary events within the CLL clone. This case demonstrates dynamic clonal selection and expansion in response to treatments, which, in turn, contributes to …

Promotion And Tenure For Medical Physicists Should Be Based On Article Specific Measures And Not On Journal Impact Factor, Samantha Hedrick, Jinzhong Yang, Yi Rong

Faculty, Staff and Student Publications

No abstract provided.

Dna Mismatch Repair Deficiency As A Biomarker In Sarcoma, Ryan A Denu, Christopher D Quintana-Perez, Sintawat Wangsiricharoen, Davis R Ingram, Khalida M Wani, Alexander J Lazar, Ravin Ratan, Christina L Roland, Y Nancy You

Faculty, Staff and Student Publications

Purpose: Lynch syndrome (LS) is a cancer predisposition syndrome caused by a germline loss-of-function mutation in a mismatch repair (MMR) gene. While sarcomas are not classically considered LS cancers, we investigated the MMR status and clinical features of sarcomas in LS patients to help inform optimal treatment strategies.

Methods: A prospectively maintained institutional clinical cancer genetics database was queried for LS patients (defined by pathogenic germline mutation in a MMR gene) with a documented diagnosis of sarcoma between 1998-2022. Tumor MMR status was determined by immunohistochemistry (IHC) for MMR proteins and secondarily by PCR assay if IHC was normal or …

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 …

Telehealth In Emergency Medicine Residency Training: A Model Curriculum, Laura Oh, Rahul Bhat, Michael J Carr, Aditi U Joshi, Bruce M Lo, Ashley C Rider, Lulu Wang, Michael C Wadman, Samuel D Luber

Faculty, Staff and Student Publications

Emergency physicians are well‐positioned to take a leadership role in telehealth, particularly in emerging categories such as triage, direct acute unscheduled care, and virtual observation. However, the growth of telehealth has outpaced curricular development in emergency medicine (EM) residency programs. This manuscript presents a model longitudinal telehealth curriculum, developed by the consensus of education experts, including representatives from the telehealth interest groups from EM's two primary specialty societies: the American College of Emergency Physicians and the Society for Academic Emergency Medicine. The curriculum describes overarching goals and components that may serve as a foundation for individual institutions seeking to train …

Skin Cancer Risk In Patients With Brca Mutations, Lucy J Navsaria, Allen M Haas, Jessica L Corredor, Banu K Arun, Sharon H Giordano, Kevin T Nead, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

3d Gamma Analysis Between Treatment Plans For Nominally Beam-Matched Medical Linear Accelerators Using Pymedphys, Fada Guan, William Donahue, Simon Biggs, Matthew Jennings, Emily Draeger, Huixiao Chen, Yuenan Wang, Ngoc Nguyen, David J Carlson, Zhe Chen, Dae Yup Han

Faculty, Staff and Student Publications

Beam-matched linear accelerators (linacs) enable flexible patient scheduling and efficient treatment delivery in the event of unexpected machine downtime. The purpose of this study was to test the feasibility of 3D gamma index as an additional metric beyond standard measurement-based comparisons for more efficient evaluation of treatment plans between linacs with nominally matched beam models to ensure safe patient transfer. Seventeen 3D conformal radiotherapy (3DCRT) plans and thirty-six volumetric-modulated radiation therapy (VMAT) plans for different disease sites were selected from the original linac. An in-house script was used to automatically create new plans for the target linac and calculate dose …

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 …

Artificial Intelligence And Machine Learning In Cancer Pain: A Systematic Review, Vivian Salama, Brandon Godinich, Yimin Geng, Laia Humbert-Vidan, Laura Maule, Kareem A Wahid, Mohamed A Naser, Renjie He, Abdallah S R Mohamed, Clifton D Fuller, Amy C Moreno

Faculty, Staff and Student Publications

Background/objectives: Pain is a challenging multifaceted symptom reported by most cancer patients. This systematic review aims to explore applications of artificial intelligence/machine learning (AI/ML) in predicting pain-related outcomes and pain management in cancer.

Methods: A comprehensive search of Ovid MEDLINE, EMBASE and Web of Science databases was conducted using terms: "Cancer," "Pain," "Pain Management," "Analgesics," "Artificial Intelligence," "Machine Learning," and "Neural Networks" published up to September 7, 2023. AI/ML models, their validation and performance were summarized. Quality assessment was conducted using PROBAST risk-of-bias andadherence to TRIPOD guidelines.

Results: Forty four studies from 2006 to 2023 were included. Nineteen studies used …

Sitravatinib In Patients With Solid Tumors Selected By Molecular Alterations: Results From A Phase Ib Study, Lyudmila Bazhenova, Dong-Wan Kim, Byoung Chul Cho, Sanjay Goel, Rebecca Heist, Theresa L Werner, Keith D Eaton, Judy S Wang, Shubham Pant, Douglas R Adkins, Collin M Blakely, Xiaohong Yan, Saskia Neuteboom, James G Christensen, Richard Chao, Todd Bauer

Faculty, Staff and Student Publications

No abstract provided.

Explainable Artificial Intelligence And Domain Adaptation For Predicting Hiv Infection With Graph Neural Networks, Evan Yu, Jingcheng Du, Yang Xiang, Xinyue Hu, Jingna Feng, Xi Luo, John A Schneider, Degui Zhi, Kayo Fujimoto, Cui Tao

Faculty, Staff and Student Publications

OBJECTIVE: Investigation of explainable deep learning methods for graph neural networks to predict HIV infections with social network information and performing domain adaptation to evaluate model transferability across different datasets.

METHODS: Network data from two cohorts of younger sexual minority men (SMM) from two U.S. cities (Chicago, IL, and Houston, TX) were collected between 2014 and 2016. Feature importance from graph attention network (GAT) models were determined using GNNExplainer. Domain adaptation was performed to examine model transferability from one city dataset to the other dataset, training with 100% of the source dataset with 30% of the target dataset and prediction …

Early Detection Of Pancreatic Cancer: Study Design And Analytical Considerations In Biomarker Discovery And Early Phase Validation Studies, Lynette M Smith, Douglas W Mahoney, William R Bamlet, Fang Yu, Suyu Liu, Michael G Goggins, Sourat Darabi, Shounak Majumder, Qiao-Li Wang, Gregory A Coté, Michael J Demeure, Zhen Zhang, Sudhir Srivastava, Akhil Chawla, Grant Izmirlian, Janet E Olson, Brian M Wolpin, Jeanine M Genkinger, Kenneth S Zaret, Randall Brand, Eugene J Koay, Ann L Oberg

Faculty, Staff and Student Publications

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that is challenging to detect at an early stage. Biomarkers are needed that can detect PDAC early in the course of disease when interventions lead to the best outcomes. We highlight study design and statistical considerations that inform pancreatic cancer early detection biomarker evaluation.

Methods: We describe experimental design strategies in this setting useful for streamlining biomarker evaluation at each Early Detection Research Network (EDRN) phase of biomarker development. We break the early EDRN phases into sub-phases, proposing objectives, study design strategies, and biomarker performance benchmarks.

Results: The goal of …

Feasibility Of An Environmental Scan-Based Approach To Collecting Information About Factors Impacting Cancer Genetics Services In Latin American Countries, Erica M Bednar, Roni Nitecki Wilke, Kirsten Jorgensen, Michael T Walsh, Stephanie Nutt, Karen H Lu, Leandro Nóbrega, Aline Patricia Soares Dias De Souza, Gabriela Da Silva Oliveira, Carlos Eduardo Mattos Da Cunha Andrade, Nelson Purizaca-Rosillo, Pamela Mora, Aldo López Blanco, Lenny N Gallardo-Alvarado, David Cantú-De León, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: Clinical cancer genetics services are expanding globally, but national policy and health care systems influence availability and implementation. Understanding the environmental factors within a country is required to appropriately implement, adapt, and evaluate cancer genetics service delivery models. An environmental scan (ES) is an approach used in business, public health, health care and other sectors to collect information about an environment or system for strategic decision making and program planning. An ES has been previously used to assess cancer genetics clinic-level factors to inform quality improvement efforts in the United States. We assessed the feasibility of using an ES …

Imipridones Inhibit Tumor Growth And Improve Survival In An Orthotopic Liver Metastasis Mouse Model Of Human Uveal Melanoma, Chandrani Chattopadhyay, Janos Roszik, Rajat Bhattacharya, Md Alauddin, Iqbal Mahmud, Sirisha Yadugiri, Mir Mustafa Ali, Fatima S Khan, Varun Vijay Prabhu, Philip L Lorenzi, Bo Wei, Elizabeth Burton, Rohini R Morey, Rossana Lazcano, Michael A Davies, Sapna P Patel, Elizabeth A Grimm

Faculty, Staff and Student Publications

Background: Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, which are CLPP activators, which inhibit OXPHOS indirectly and have demonstrated safety in patients.

Methods: We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201 and ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic efficacy in vivo in UM liver metastasis models.

Results: CLPP expression was detected in primary …

Pathobiology Of Myocardial And Cardiomyocyte Injury In Ischemic Heart Disease: Perspective From Seventy Years Of Cell Injury Research, L Maximilian Buja

Faculty, Staff and Student Publications

This review presents a perspective on the pathobiology of acute myocardial infarction, a major manifestation of ischemic heart disease, and related mechanisms of ischemic and toxic cardiomyocyte injury, based on advances and insights that have accrued over the last seventy years, including my sixty years of involvement in the field as a physician-scientist-pathologist. This analysis is based on integration of my research within the broader context of research in the field. A particular focus has been on direct measurements in cardiomyocytes of electrolyte content by electron probe X-ray microanalysis (EPXMA) and Ca2+ fluxes by fura-2 microspectrofluorometry. These studies established that …

Gravity- Vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study, Samira Shojaee, Jasleen Pannu, Lonny Yarmus, Alberto Fantin, Christina Macrosty, Roland Bassett, Labib Debiane, Zachary S Depew, Saadia A Faiz, Carlos A Jimenez, Sameer K Avasarala, Erik Vakil, Andrew Demaio, Lara Bashoura, Keerthana Keshava, Travis Ferguson, Roberto Adachi, George A Eapen, David E Ost, Sami Bashour, Asad Khan, Vickie Shannon, Ajay Sheshadri, Roberto F Casal, Scott E Evans, Krystle Pew, Nadia Castaldo, Diwakar D Balachandran, Vincenzo Patruno, Robert Lentz, Cheryl Pai, Fabien Maldonado, Lance Roller, Junsheng Ma, Jhankruti Zaveri, Jenna Los, Luis Vaquero, Eva Ordonez, Gulmira Yermakhanova, Jason Akulian, Cole Burks, Roel-Rolando Almario, Marie Sauve, Jackson Pettee, Laila Z Noor, Muhammad H Arain, Horiana B Grosu

Faculty, Staff and Student Publications

Background: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated.

Research question: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis?

Study design and methods: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction …

Body Composition In Recurrent Prostate Cancer And The Role Of Steroidogenic Genotype, Neha Venkatesh, Rebecca S Tidwell, Yao Yu, Ana Aparicio, Amado J Zurita, Sumit K Subudhi, Bilal A Siddiqui, Sagar S Mukhida, Justin R Gregg, Paul G Corn, Efstratios Koutroumpakis, Jennifer L Mcquade, Daniel E Frigo, Patrick G Pilie, Chad Huff, Christopher J Logothetis, Andrew W Hahn

Faculty, Staff and Student Publications

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: i) CT imaging of L3 prior to and after treatment; and ii) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. …

Contemporary Approach To The Diagnosis And Classification Of Myelodysplastic Neoplasms/Syndromes-Recommendations From The International Consortium For Myelodysplastic Neoplasms/Syndromes (Mds [Icmds]), Fnu Aakash, Savanah D Gisriel, Amer M Zeidan, John M Bennett, Rafael Bejar, Jan Philipp Bewersdorf, Uma M Borate, Jacqueline Boultwood, Andrew M Brunner, Rena Buckstein, Hetty E Carraway, Jane E Churpek, Naval G Daver, Amy E Dezern, Fabio Efficace, Pierre Fenaux, Maria E Figueroa, Guillermo Garcia-Manero, Steven D Gore, Peter L Greenberg, Elizabeth A Griffiths, Stephanie Halene, Christopher S Hourigan, Tae Kon Kim, Nina Kim, Rami S Komrokji, Vijay K Kutchroo, Alan F List, Richard F Little, Ravindra Majeti, Aziz Nazha, Stephen D Nimer, Olatoyosi Odenike, Eric Padron, Mrinal M Patnaik, Uwe Platzbecker, Matteo G Della Porta, Gail J Roboz, David A Sallman, Valeria Santini, Guillermo Sanz, Michael R Savona, Mikkael A Sekeres, Maximilian Stahl, Daniel T Starczynowski, David P Steensma, Justin Taylor, Omar Abdel-Wahab, Andrew H Wei, Zhuoer Xie, Mina L Xu, Robert P Hasserjian, Sanam Loghavi

Faculty, Staff and Student Publications

Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of biologically distinct entities characterized by variable degrees of ineffective hematopoiesis. Recently, 2 classification systems (the 5th edition of the World Health Organization Classification of Haematolymphoid tTumours and the International Consensus Classification) further subcharacterized MDS into morphologically and genetically defined groups. Accurate diagnosis and subclassification of MDS require a multistep systemic approach. The International Consortium for MDS (icMDS) summarizes a contemporary, practical, and multimodal approach to MDS diagnosis and classification.

Early-Stage Extranodal Nk/T-Cell Lymphoma, Nasal Type: A Role For Elective Nodal Irradiation?, Penny Fang, Sonal S Noticewala, Susan Y Wu, Jillian R Gunther, Ethan B Ludmir, L Jeffrey Medeiros, Paolo Strati, Ranjit Nair, Chijioke Nze, Loretta J Nastoupil, Sairah Ahmed, Luis Malpica Castillo, Luis Fayad, Jason Westin, Sattva Neelapu, Christopher Flowers, Auris Huen, Swaminathan P Iyer, Bouthaina Dabaja, Chelsea C Pinnix

Faculty, Staff and Student Publications

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

Methods and materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States.

Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective …

Mortality Risks Associated With Depression In Men With Prostate Cancer, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

Design, setting, and participants: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018.

Outcome measurements and …

Adjuvant Rituximab And Elevated Intratumoural Cd8 Expression Are Associated With Sustained Disease Control After Radiotherapy In A Randomised Trial Of Systemic Therapy In Early-Stage Follicular Lymphoma, Michael P Macmanus, John F Seymour, Hennes Tsang, Richard Fisher, Colm Keane, Muhammed B Sabdia, Soi C Law, Jay Gunawardana, Karthik Nath, Stephen H Kazakoff, Mario L Marques-Piubelli, Daniela E Duenas, Michael R Green, Daniel Roos, Peter O'Brien, Andrew Mccann, Richard Tsang, Sidney Davis, David Christie, Chan Cheah, Benhur Amanuel, Tara Cochrane, Jason Butler, Anna Johnston, Mohamed Shanavas, Li Li, Claire Vajdic, Robert Kridel, Victoria Shelton, Samantha Hershenfield, Tara Baetz, David Lebrun, Nathalie Johnson, Marianne Brodtkorb, Maja Ludvigsen, Francesco D'Amore, Ella R Thompson, Piers Blombery, Maher K Gandhi, Joshua W D Tobin

Faculty, Staff and Student Publications

Background: We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.

Methods: Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).

Findings: Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at …

The Prognostic Impact Of Tumor Deposits In Colorectal Cancer: More Than Just N1c, Neal Bhutiani, Oliver Peacock, Abhineet Uppal, Chung-Yuan Hu, Brian K Bednarski, Melissa W Taggart, Arvind Dasari, Van K Morris, Harmeet Kaur, Scott Kopetz, Emma B Holliday, Prajnan Das, Y Nancy You, George J Chang

Faculty, Staff and Student Publications

Background: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC.

Methods: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards …

Mimosa: A Resource Consisting Of Improved Methylome Prediction Models Increases Power To Identify Dna Methylation-Phenotype Associations, Hunter J Melton, Zichen Zhang, Hong-Wen Deng, Lang Wu, Chong Wu

Faculty, Staff and Student Publications

Although DNA methylation (DNAm) has been implicated in the pathogenesis of numerous complex diseases, from cancer to cardiovascular disease to autoimmune disease, the exact methylation sites that play key roles in these processes remain elusive. One strategy to identify putative causal CpG sites and enhance disease etiology understanding is to conduct methylome-wide association studies (MWASs), in which predicted DNA methylation that is associated with complex diseases can be identified. However, current MWAS models are primarily trained using the data from single studies, thereby limiting the methylation prediction accuracy and the power of subsequent association studies. Here, we introduce a new …

Wirelessly Actuated Microfluidic Pump And Valve For Controlled Liquid Delivery In Dental Implants, Yilan Xu, Honglu Lin, Boyang Xiao, Hutomo Tanoto, Joel Berinstein, Alend Khoshnaw, Simon Young, Yuxiao Zhou, Xiaoguang Dong

Faculty, Staff and Student Publications

Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (< 65 mT), are reported. A magnet-screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52 µL in a dental implant. The liquid cargos are delivered directly to the implant-bone interface, a region traditionally difficult to access. On-demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long-term and targeted delivery of therapeutic agents in various bioengineering applications.