Medicine and Health Sciences Commons^™

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …

The Influence Of Home Versus Clinic Anal Human Papillomavirus Sampling On High-Resolution Anoscopy Uptake In The Prevent Anal Cancer Self-Swab Study, Jenna Nitkowski, Timothy J Ridolfi, Sarah J Lundeen, Anna R Giuliano, Elizabeth Y Chiao, Maria E Fernandez, Vanessa Schick, Jennifer S Smith, Bridgett Brzezinski, Alan G Nyitray

Faculty, Staff and Student Publications

Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results …

Differential Effects Of Type 2 Diabetes Treatment Regimens On Diabetes Distress And Depressive Symptoms In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Jeffrey S Gonzalez, Ionut Bebu, Heidi Krause-Steinrauf, Claire J Hoogendoorn, Gladys Crespo-Ramos, Caroline Presley, Aanand D Naik, Shihchen Kuo, Mary L Johnson, Deborah Wexler, Jill P Crandall, Anne E Bantle, Valerie Arends, Andrea L Cherrington

Faculty, Staff and Student Publications

Objective: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments.

Research design and methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of < 10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up.

Results: Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms.

Conclusions: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults …

Does Emotional Distress Predict Worse Glycemic Control Over Time? Results From The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Andrea L Cherrington, Ionut Bebu, Heidi Krause-Steinrauf, Claire J Hoogendoorn, Gladys Crespo-Ramos, Caroline Presley, Aanand D Naik, Ashok Balasubramanyam, Michaela R Gramzinski, Tina Killean, Valerie L Arends, Jeffrey S Gonzalez

Faculty, Staff and Student Publications

Objective: To evaluate whether baseline levels of depressive symptoms and diabetes-specific distress are associated with glycemic control in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing the metabolic effects of four common glucose-lowering medications when combined with metformin in individuals with type 2 diabetes mellitus (T2DM).

Research design and methods: The primary and secondary outcomes were defined as an HbA1c value ≥7%, subsequently confirmed, and an HbA1c value >7.5%, subsequently confirmed, respectively. Separate Cox proportional hazards models assessed the association between baseline levels of each exposure of interest (depressive symptoms measured with …

Emotional Distress Predicts Reduced Type 2 Diabetes Treatment Adherence In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Claire J Hoogendoorn, Heidi Krause-Steinrauf, Diane Uschner, Hui Wen, Caroline A Presley, Elizabeth A Legowski, Aanand D Naik, Sherita Hill Golden, Valerie L Arends, Janet Brown-Friday, Jonathan A Krakoff, Colleen E Suratt, Andrea H Waltje, Andrea L Cherrington, Jeffrey S Gonzalez

Faculty, Staff and Student Publications

Objective: We examined longitudinal associations between emotional distress (specifically, depressive symptoms and diabetes distress) and medication adherence in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing four glucose-lowering medications added to metformin in adults with relatively recent-onset type 2 diabetes mellitus (T2DM).

Research design and methods: The Emotional Distress Substudy assessed medication adherence, depressive symptoms, and diabetes distress in 1,739 GRADE participants via self-completed questionnaires administered biannually up to 3 years. We examined baseline depressive symptoms and diabetes distress as predictors of medication adherence over 36 months. Bidirectional visit-to-visit relationships were also …

Concordance Of Human Papillomavirus Genotypes In Mailed Home-Based Self-Collected Versus Clinician-Collected Anal Swabs Among Sexual And Gender Minority Individuals, Jenna Nitkowski, Anna R Giuliano, Tim Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Michael D Swartz, Jennifer S Smith, Alan G Nyitray

Faculty, Staff and Student Publications

Background: Home-based self-sampling may be a viable option for anal cancer screening among sexual minority men (SMM). Yet limited research has compared home-based self-collected with clinician-collected anal swabs for human papillomavirus (HPV) genotyping.

Methods: The Prevent Anal Cancer Self-Swab Study recruited SMM and transgender persons 25 years and over in Milwaukee, WI to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal self-sampling kit to complete and return via postal mail. They were also asked to attend a clinic appointment where a clinician collected an anal swab. …

Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19.

METHODS: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention …

Maintaining Program Fidelity In A Changing World: National Implementation Of A School-Based Hiv Prevention Program, Elizabeth Schieber, Lynette Deveaux, Lesley Cotrell, Xiaoming Li, Stephenie C Lemon, Arlene S Ash, Karen Macdonell, Samiran Ghosh, Maxwell Poitier, Glenda Rolle, Sylvie Naar, Bo Wang

Faculty, Staff and Student Publications

Large-scale, evidence-based interventions face challenges to program fidelity of implementation. We developed implementation strategies to support teachers implementing an evidence-based HIV prevention program in schools, Focus on Youth in The Caribbean (FOYC) and Caribbean Informed Parents and Children Together (CImPACT) in The Bahamas. We examined the effects of these implementation strategies on teachers' implementation in the subsequent year after the initial implementation during the COVID-19 pandemic. Data were collected from 79 Grade 6 teachers in 24 government elementary schools. Teachers completed training workshops and a pre-implementation questionnaire to record their characteristics and perceptions that might affect their program fidelity. School …

Premastectomy Radiotherapy And Immediate Breast Reconstruction: A Randomized Clinical Trial, Mark V Schaverien, Puneet Singh, Benjamin D Smith, Wei Qiao, Catherine L Akay, Elizabeth S Bloom, Mariana Chavez-Macgregor, Carrie K Chu, Mark W Clemens, Jessica S Colen, Richard A Ehlers, Rosa F Hwang, Melissa M Joyner, Rene D Largo, Alexander F Mericli, Melissa P Mitchell, John W Shuck, Nina Tamirisa, Debasish Tripathy, Mark T Villa, Wendy A Woodward, Rensi Zacharia, Henry M Kuerer, Karen E Hoffman

Faculty, Staff and Student Publications

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This …

The Peer To Career Pipeline: An Observational Study Of Peer Worker Trainee Characteristics And Training Completion Likelihood, Sierra Castedo De Martell, J Michael Wilkerson, Jason Howell, H Shelton Brown, Nalini Ranjit, Lori Holleran Steiker, Sheryl A Mccurdy

Faculty, Staff and Student Publications

Introduction: Peer recovery support services (PRSS) for substance use disorder (SUD) are a flexible and evidence-based intervention employed across multiple settings and for a variety of populations. These services have expanded over the past two decades, but there is little research on recruitment and training of prospective peer workers - the peer to career pipeline. This study observed training outcomes for applicants to a peer worker scholarship program in Texas.

Methods: A total of 448 participants provided baseline personal history information, and a subset of participants (n = 239) completed optional psychosocial surveys. Logistic regression analysis tested associations of personal …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

Efficacy Of Behavioral Economic Nudges To Assist Teen Mothers: The Healthy Adolescent Transitions Randomized Controlled Trial., Jack Stevens, Joseph Rausch, Robyn Lutz, Ngozi Osuagwu

Women’s Health Articles

Communities may often lack the resources to deliver intensive programs to assist teen mothers, and many eligible adolescents may decline participation in lengthy interventions. Therefore, alternative approaches involving less resource and time may be needed. Behavioral economics (BE) can inform the development of such novel interventions. BE often feature low-intensity approaches designed to "nudge" people to help them reach their long-term goals. Nudges can include giving reminders, making the desired behavior more convenient, and optimizing the verbal presentation of recommended options. Three hundred thirty-one American adolescents (ages 14 to 19) who were 22 to 35 weeks pregnant were enrolled in …

Reciprocal Relationships Between Stress And Depressive Symptoms: The Essential Role Of The Nucleus Accumbens, Yizhou Ma, Peter Kochunov, Mark D Kvarta, Tara Legates, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E Nichols, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and …

Presentation Acuity And Surgical Outcomes For Patients With Health Insurance Living In Highly Deprived Neighborhoods, Susanne Schmidt, Michael A Jacobs, Jeongsoo Kim, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Importance: Insurance coverage expansion has been proposed as a solution to improving health disparities, but insurance expansion alone may be insufficient to alleviate care access barriers.

Objective: To assess the association of Area Deprivation Index (ADI) with postsurgical textbook outcomes (TO) and presentation acuity for individuals with private insurance or Medicare.

Design, setting, and participants: This cohort study used data from the National Surgical Quality Improvement Program (2013-2019) merged with electronic health record data from 3 academic health care systems. Data were analyzed from June 2022 to August 2023.

Exposure: Living in a neighborhood with an ADI greater than 85. …

Ems Treatment Guidelines In Major Traumatic Brain Injury With Positive Pressure Ventilation, Joshua B Gaither, Daniel W Spaite, Bentley J Bobrow, Bruce Barnhart, Vatsal Chikani, Kurt R Denninghoff, Gail H Bradley, Amber D Rice, Jeffrey T Howard, Samuel M Keim, Chengcheng Hu

Faculty, Staff and Student Publications

Importance: The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown.

Objective: To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV.

Design, setting, and participants: The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and …

Survey Of Neonatal Management After Amnioinfusion For Anhydramnios, Ellen M Bendel-Stenzel, Amaris M Keiser, Kristin J Mckenna, Valerie Y Chock, Suzanne Lopez, Jena L Miller, Meredith A Atkinson

Faculty, Staff and Student Publications

No abstract provided.

Temporal Changes In Treatment And Late Mortality And Morbidity In Adult Survivors Of Childhood Glioma: A Report From The Childhood Cancer Survivor Study, Peter M K De Blank, Katharine R Lange, Mengqi Xing, Sedigheh Mirzaei Salehabadi, Deokumar Srivastava, Tara M Brinkman, Kirsten K Ness, Kevin C Oeffinger, Joseph Neglia, Kevin R Krull, Paul C Nathan, Rebecca Howell, Lucie M Turcotte, Wendy Leisenring, Gregory T Armstrong, M Fatih Okcu, Daniel C Bowers

Faculty, Staff and Student Publications

Pediatric glioma therapy has evolved to delay or eliminate radiation for low-grade tumors. This study examined these temporal changes in therapy with long-term outcomes in adult survivors of childhood glioma. Among 2,501 5-year survivors of glioma in the Childhood Cancer Survivor Study diagnosed 1970-1999, exposure to radiation decreased over time. Survivors from more recent eras were at lower risk of late mortality (≥5 years from diagnosis), severe/disabling/life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs). Adjusting for treatment exposure (surgery only, chemotherapy, or any cranial radiation) attenuated this risk (for example, CHCs (1990s versus 1970s), relative risk (95% confidence interval), …

Oral Decitabine And Cedazuridine Plus Venetoclax For Older Or Unfit Patients With Acute Myeloid Leukaemia: A Phase 2 Study, Alexandre Bazinet, Guillermo Garcia-Manero, Nicholas Short, Yesid Alvarado, Alex Bataller, Tareq Abuasab, Rabiul Islam, Kathryn Montalbano, Ghayas Issa, Abhishek Maiti, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Guillermo Montalban-Bravo, Caitlin R Rausch, Sherry Pierce, Courtney D Dinardo, Tapan Kadia, Naval Daver, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax.

Methods: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. …

Trajectories Of Health Care Contact Days For Patients With Stage Iv Non-Small Cell Lung Cancer, Arjun Gupta, Paul Nguyen, Danielle Kain, Andrew G Robinson, Amit A Kulkarni, David H Johnson, Carolyn J Presley, Anne H Blaes, Gabrielle B Rocque, Ishani Ganguli, Christopher M Booth, Timothy P Hanna

Faculty, Staff and Student Publications

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC.

Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice.

Design, setting, and participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 …

Clinical Management, Monitoring, And Prophylaxis Of Adverse Events Of Special Interest Associated With Datopotamab Deruxtecan, Rebecca S Heist, Jacob Sands, Aditya Bardia, Toshio Shimizu, Aaron Lisberg, Ian Krop, Noboru Yamamoto, Takahiro Kogawa, Saba Al-Hashimi, Simon S M Fung, Anat Galor, Francesca Pisetzky, Priyanka Basak, Cindy Lau, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in …

Neuroendocrine Neoplasms Of The Ovary: A Review Of 63 Cases, Alejandra Flores Legarreta, Reem Saab, Naomi R Gonzales, Gary B Chisholm, Shannon N Westin, R Tyler Hillman, Michael Frumovitz

Faculty, Staff and Student Publications

Objective: To describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry.

Methods: This is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine neoplasms. We excluded patients with small cell carcinoma not otherwise specified, small cell hypercalcemic type, and those with neuroendocrine 'features' or 'differentiation.' Clinicopathological characteristics were described in two separate groups: patients with carcinoid tumors and patients with neuroendocrine carcinomas. Progression-free and overall survival were estimated with the Kaplan-Meier product-limit estimator in these two groups, and multivariable analysis was done to identify predictors of survival for neuroendocrine carcinomas …

Comparison Of Comorbidity Models Within A Population-Based Cohort Of Older Adults With Non-Hodgkin Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Swaminathan Iyer, Alessandra Ferrajoli, Alexey V Danilov, Sharon H Giordano

Faculty, Staff and Student Publications

Purpose: Compare the association of individual comorbidities, comorbidity indices, and survival in older adults with non-Hodgkin lymphoma (NHL), including in specific NHL subtypes.

Methods: Data source was SEER-Medicare, a population-based registry of adults age 65 years and older with cancer. We included all incident cases of NHL diagnosed during 2008-2017 who met study inclusion criteria. Comorbidities were classified using the three-factor risk estimate scale (TRES), Charlson comorbidity index (CCI), and National Cancer Institute (NCI) comorbidity index categories and weights. Overall survival (OS) and lymphoma-specific survival, with death from other causes treated as a competing risk, were estimated using the Kaplan-Meier …

Reduced Dose Azacitidine Plus Venetoclax As Maintenance Therapy In Acute Myeloid Leukaemia Following Intensive Or Low-Intensity Induction: A Single-Centre, Single-Arm, Phase 2 Trial, Alexandre Bazinet, Hagop Kantarjian, Alex Bataller, Naveen Pemmaraju, Gautam Borthakur, Kelly Chien, Yesid Alvarado, Prithviraj Bose, Elias Jabbour, Musa Yilmaz, Courtney Dinardo, Ghayas Issa, Guillermo Montalban-Bravo, Nicholas Short, Koji Sasaki, Debra Bull-Linderman, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.

Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible …

Oral Decitabine And Cedazuridine Plus Venetoclax For Older Or Unfit Patients With Acute Myeloid Leukaemia: A Phase 2 Study, Alexandre Bazinet, Guillermo Garcia-Manero, Nicholas Short, Yesid Alvarado, Alex Bataller, Tareq Abuasab, Rabiul Islam, Kathryn Montalbano, Ghayas Issa, Abhishek Maiti, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Guillermo Montalban-Bravo, Caitlin R Rausch, Sherry Pierce, Courtney D Dinardo, Tapan Kadia, Naval Daver, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

BACKGROUND: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax.

METHODS: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. …

Cochlear Implantation After Head And Neck Radiation: A Case Series, Systematic Review, And Meta-Analysis, Jumah G Ahmad, Benjamin D Lovin, Anna Lee, Marc-Elie Nader, Paul W Gidley

Faculty, Staff and Student Publications

Objective: To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in this population through a retrospective cohort review, systematic review, and meta-analysis.

Databases reviewed: PubMed, Cochrane Library, and Embase.

Methods: We retrospectively reviewed all CI cases after head and neck (HN) XRT at our institution, noting intraoperative findings, postoperative complications, and hearing outcomes. Change in speech discrimination scores (SDSs) was the primary outcome measure. Systematic review was performed to identify all cases of CI after HNXRT. A meta-analysis was performed to assess SDS change.

Results: The …

Incidence And Presenting Characteristics Of Angiosarcoma In The Us, 2001-2020, Michael J Wagner, Vinod Ravi, Stephanie K Schaub, Ed Y Kim, Jeremy Sharib, Harveshp Mogal, Min Park, Michaela Tsai, Daniela Duarte-Bateman, Anthony Tufaro, Elizabeth T Loggers, Lee D Cranmer, Bonny Chau, Michael J Hassett, Juneko Grilley-Olson, Kelly G Paulson

Faculty, Staff and Student Publications

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed.

Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US.

Design, setting, and participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in …

Randomized Phase 2 Trial Of Tremelimumab And Durvalumab In Combination Versus Sequentially In Recurrent Platinum-Resistant Ovarian Cancer, Emily M Hinchcliff, Anne Knisely, Naomi Adjei, Bryan Fellman, Ying Yuan, Ami Patel, Cai Xu, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Nicole D Fleming, David M Gershenson, Raghunandan Vikram, Tharakeswara Bathala, David Vining, Dhakshina M Ganeshan, Karen H Lu, Charlotte C Sun, Larissa A Meyer, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end …

Genome-Wide Crispr Screen Reveals The Synthetic Lethality Between Bcl2l1 Inhibition And Radiotherapy, Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 …

Automatic End-To-End Vmat Treatment Planning For Rectal Cancers, Kai Huang, Christine Chung, Ethan B Ludmir, Lifei Zhang, Constance A Owens, Jean Gumma-De La Vega, Jack Duryea, Yao Zhao, Xinru Chen, David Fuentes, Carlos E Cardenas, Tina Marie Briere, Sam Beddar, Laurence E Court, Prajnan Das

Faculty, Staff and Student Publications

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear.

PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs.

METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …