Medical Specialties Commons^™

Machine Learning Reveals Lipidome Remodeling Dynamics In A Mouse Model Of Ovarian Cancer, Olatomiwa O Bifarin, Samyukta Sah, David A Gaul, Samuel G Moore, Ruihong Chen, Murugesan Palaniappan, Jaeyeon Kim, Martin M Matzuk, Facundo M Fernández

Faculty, Staff and Students Publications

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. …

Long-Term Outcomes Of Dual Vs Single Her2-Directed Neoadjuvant Therapy In Nsabp B-41., Priya Rastogi, Gong Tang, Saima Hassan, Charles E Geyer, Catherine A Azar, Gustav C Magrinat, J Marie Suga, Harry D Bear, Luis Baez-Diaz, Shakir Sarwar, Jean-Francois Boileau, Adam M Brufsky, Henry R Shibata, Hanna Bandos, Soonmyung Paik, Greg Yothers, Sandra M Swain, Eleftherios P Mamounas, Norman Wolmark

Oncology Articles

BACKGROUND: The primary aim of this randomized neoadjuvant trial in operable, HER2-positive breast cancer, was to determine the efficacy on pathologic complete response (pCR) of substituting lapatinib (L) for trastuzumab (T) or adding L to T, in combination with weekly paclitaxel (WP) following AC. Results on pCR were previously reported. Here, we report data on planned secondary endpoints, recurrence-free interval (RFI) post-surgery, and overall survival (OS).

METHODS: All patients received standard AC q3 weeks × 4 cycles followed by WP (80 mg/m

RESULTS: RFI at 4.5 years was 87.2%, 79.4% (p = 0.34; HR = 1.37; 95% CI 0.80, 2.34), …

Camonsertib In Dna Damage Response-Deficient Advanced Solid Tumors: Phase 1 Trial Results, Timothy A Yap, Elisa Fontana, Elizabeth K Lee, David R Spigel, Martin Højgaard, Stephanie Lheureux, Niharika B Mettu, Benedito A Carneiro, Louise Carter, Ruth Plummer, Gregory M Cote, Funda Meric-Bernstam, Joseph O'Connell, Joseph D Schonhoft, Marisa Wainszelbaum, Adrian J Fretland, Peter Manley, Yi Xu, Danielle Ulanet, Victoria Rimkunas, Mike Zinda, Maria Koehler, Ian M Silverman, Jorge S Reis-Filho, Ezra Rosen

Faculty, Staff and Student Publications

Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose …

Phase Ii Trial Of Nelipepimut-S Peptide Vaccine In Women With Ductal Carcinoma In Situ, Anne E O'Shea, Guy T Clifton, Na Qiao, Brandy M Heckman-Stoddard, Malgorzata Wojtowicz, Eileen Dimond, Isabelle Bedrosian, Diane Weber, Judy E Garber, Alexander Husband, Ricardo Pastorello, J Jack Lee, Mike Hernandez, Diane D Liu, Lana A Vornik, Powel H Brown, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in …

Efficacy Of Systemic Chemotherapy In Patients With Low-Grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial, John Paul Shen, Abdelrahman M Yousef, Fadl A Zeineddine, Mohammad A Zeineddine, Rebecca S Tidwell, Karen A Beaty, Lisa C Scofield, Safia Rafeeq, Nicholas Hornstein, Elizabeth Lano, Cathy Eng, Aurelio Matamoros, Wai Chin Foo, Abhineet Uppal, Christopher Scally, Paul Mansfield, Melissa Taggart, Kanwal P Raghav, Michael J Overman, Keith Fournier

Faculty, Staff and Student Publications

IMPORTANCE: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease.

OBJECTIVE: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was …

Ovarian Cancer Pathology Characteristics As Predictors Of Variant Pathogenicity In Brca1 And Brca2, Denise G O'Mahony, Susan J Ramus, Melissa C Southey, Nicola S Meagher, Andreas Hadjisavvas, Esther M John, Ute Hamann, Evgeny N Imyanitov, Irene L Andrulis, Priyanka Sharma, Mary B Daly, Christopher R Hake, Jeffrey N Weitzel, Anna Jakubowska, Andrew K Godwin, Adalgeir Arason, Anita Bane, Jacques Simard, Penny Soucy, Maria A Caligo, Phuong L Mai, Kathleen B M Claes, Manuel R Teixeira, Wendy K Chung, Conxi Lazaro, Peter J Hulick, Amanda E Toland, Inge Sokilde Pedersen, Susan L Neuhausen, Ana Vega, Miguel De La Hoya, Heli Nevanlinna, Mallika Dhawan, Valentina Zampiga, Rita Danesi, Liliana Varesco, Viviana Gismondi, Valerio Gaetano Vellone, Paul A James, Ramunas Janavicius, Liene Nikitina-Zake, Finn Cilius Nielsen, Thomas Van Overeem Hansen, Tanja Pejovic, Ake Borg, Johanna Rantala, Kenneth Offit, Marco Montagna, Katherine L Nathanson, Susan M Domchek, Ana Osorio, María J García, Beth Y Karlan, Gemo Study Collaborators, Anna De Fazio, David Bowtell, Aocs Group, Lesley Mcguffog, Michael T Parsons, Thilo Dörk, Lisa-Marie Speith, Elizabeth Santana Dos Santos, Alexandre André B A Da Costa, Paolo Radice, Paolo Peterlongo, Laura Papi, Christoph Engel, Eric Hahnen, Rita K Schmutzler, Barbara Wappenschmidt, Douglas F Easton, Marc Tischkowitz, Christian F Singer, Yen Yen Tan, Alice S Whittemore, Weiva Sieh, James D Brenton, Drakoulis Yannoukakos, Florentia Fostira, Irene Konstantopoulou, Jana Soukupova, Michal Vocka, Czecanca Consortium, Georgia Chenevix-Trench, Paul D P Pharoah, Antonis C Antoniou, David E Goldgar, Amanda B Spurdle, Kyriaki Michailidou, Consortium Of Investigators Of Modifiers Of Brca1/2, Evidence-Based Network For The Interpretation Of Germline Mutant Alleles Consortium, Hebon Investigators, Goska Leslie

Faculty, Staff and Student Publications

BACKGROUND: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.

METHODS: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with …

Clinical Outcomes Of Leuprolide Acetate In The Treatment Of Recurrent Ovarian Granulosa Cell Tumors, Katherine I Foster, Alejandra Flores Legarreta, Rhea Kamat, Katelyn F Handley, Deanna Glassman, Jeffrey A How, Barrett C Lawson, Shannon N Westin, Lois M Ramondetta, Michael Frumovitz, David M Gershenson, Anil K Sood, R Tyler Hillman

Faculty, Staff and Student Publications

BACKGROUND: The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach.

OBJECTIVE: This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors.

STUDY DESIGN: This was a retrospective cohort study of patients enrolled in the Rare Gynecologic Malignancy Registry at a large cancer referral center and affiliated county hospital. Patients meeting …

Uptake And Outcomes Of Neoadjuvant Chemotherapy Among Us Patients With Less Common Epithelial Ovarian Carcinomas, Koji Matsuo, Shinya Matsuzaki, Michihide Maeda, Alesandra R Rau, Kosuke Yoshihara, Ryo Tamura, Muneaki Shimada, Hiroko Machida, Mikio Mikami, Maximilian Klar, Lynda D Roman, Jason D Wright, Anil K Sood, David M Gershenson

Faculty, Staff and Student Publications

Importance: Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.

Objective: To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.

Design, setting, and participants: A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed …

Integration Of Remote Symptom And Biometric Monitoring Into The Care Of Adult Patients With Cancer Receiving Chemotherapy-A Decentralized Feasibility Pilot Study, Anaeze C Offodile, Domenica Delgado, Yu-Li Lin, Danielle Geyen, Christopher J Miller, Sanchita Jain, Janice P Finder, Sanjay Shete, Frank V Fossella, Michael J Overman, Susan K Peterson

Faculty, Staff and Student Publications

PURPOSE: Although electronic patient-reported outcomes (ePROs) are efficacious in symptom management, much is unknown about the utility of vital signs surveillance. We examined the feasibility of a remote patient monitoring platform that integrates ePROs and biometrics into the ambulatory management of symptom burden.

METHODS: Using a decentralized workflow, patients with gastrointestinal or thoracic cancer were approached for a 1-month study. Patients reported symptom burden via ePROs and biometrics (blood pressure, oxygen saturation, pulse, weight, and temperature) using bluetooth-enabled devices daily. Alerts on the basis of prespecified thresholds were managed via nurse-led triage. Adherence was defined as the completion of > 70% …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Comparison Of Female Ovarian Reserve Before Vs After Covid-19 Vaccination, Liubin Yang, Samantha Neal, Tiffany Lee, Andrew Chou, Amy K Schutt, William Gibbons

Children’s Nutrition Research Center Staff Publications

This cohort study examines the association of COVID-19 vaccination with levels of anti-Mullerian hormone and antral follicle count in women seeking fertility treatment.

The Effects Of Gender And Country Of Origin On Acculturation, Psychological Factors, Lifestyle Factors, And Diabetes-Related Physiological Outcomes Among Mexican Americans: The Starr County Diabetes Prevention Initiative, Sharon A Brown, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, Mary A Winter, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

OBJECTIVES: Examine acculturation and psychological, lifestyle, and physiological factors based on gender and country of origin (U.S. vs. Mexico).

METHODS: Baseline data from the Starr County diabetes prevention study (

RESULTS: Participants were: predominantly female (73%); 51 years of age, on average; born in Mexico (71%); and Spanish-speaking. Individuals spent 11 of their waking hours (range = 0-18 h) in sedentary activities. Compared to females, more males spoke English and reported fewer hours in sedentary activities. Compared to participants born in Mexico, those born in the U.S. were more likely to: speak English; report depressive symptoms; and exhibit elevated BMI …

Cross-Sectional Association Between Neighborhood Socioeconomic Status And Sleep Duration Among Black And White Men And Women: The Southern Community Cohort Study, Samuel H Nyarko, Liying Luo, David G Schlundt, Qian Xiao

Faculty, Staff and Student Publications

Objective: To examine the association of neighborhood socioeconomic status (SES) with sleep duration among a large cohort of Black and white men and women in the United States.

Methods: We used data from the Southern Community Cohort Study (SCCS, N = 75,248). Neighborhood SES was based on census data and sleep duration was measured by self-report. Multinomial logistic regression analysis was performed to assess the association between neighborhood SES and short (<7 hours) and long (≥9 hours) sleep in the overall sample and according to race-sex subgroups.

Results: In the total sample, when compared with the highest quintile of neighborhood SES, the lowest quintile was associated with higher odds of both short (adjusted ORQ5 vs. …

Diabetes-Related Quality Of Life Assessment In Children Following Total Pancreatectomy With Islet Autotransplantation., Jacob M. Redel, Lindsey Hornung, Deborah Elder, Jaimie D. Nathan, Sarah Corathers, Kristin L. Rich, Maisam Abu-El-Haija

Manuscripts, Articles, Book Chapters and Other Papers

Total pancreatectomy with islet autotransplantation (TPIAT) can improve pain and reduce functional impairment associated with acute recurrent or chronic pancreatitis. However, long-term glucose monitoring and insulin therapy are often required, which can adversely affect the quality of life. We sought to evaluate diabetes-related quality of life (DR-QOL) in youth who underwent TPIAT and compare it to the youth with new-onset type 1 diabetes (T1D). The Pediatric Quality of Life Inventory™ 3.2 Diabetes Module (PedsQL™ DM) was used to assess DR-QOL in 46 youth (< 20 years old) who underwent TPIAT. The PedsQL™ DM scores were analyzed for statistically significant changes and minimally important clinical differences (MCID) over time post-TPIAT. Scores at 12 months (n = 52) and 24 months (n = 58) after diagnosis of T1D. The diabetes …

Recruitment And Reach In A School-Based Pediatric Obesity Intervention Trial In Rural Areas., Bethany Forseth, Brittany Lancaster, Megan Olalde, Christie A. Befort, Rebecca E. Swinburne Romine, Meredith Dreyer, Kelsey Dean, Eve-Lynn Nelson, Ann M. Davis

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas.

METHODS: Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing …

Sex- And Ethnic-Specific Patterns In The Incidence Of Hip Fracture Among Older Us Asian And Non-Hispanic White Adults, Joan C Lo, Malini Chandra, David R Lee, Jeanne A Darbinian, Nancy P Gordon, David W Zeltser, Christopher D Grimsrud, Catherine Lee

Faculty, Staff and Student Publications

BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences.

METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence …

The Tgf-Β Superfamily As Potential Therapeutic Targets In Pancreatic Cancer, William A Grobman, Grecio J Sandoval, Torri D Metz, Tracy A Manuck, Rebecca G Clifton, Brenna L Hughes, George R Saade, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N Simhan, Dwight J Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L Bailit, Maged M Costantine, Harish M Sehdev, Alan T N Tita, George A Macones

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether preterm birth rates changed in relation to the onset of the coronavirus disease 2019 (COVID-19) pandemic and whether any change depended on socioeconomic status.

METHODS: This is an observational cohort study of pregnant individuals with a singleton gestation who delivered in the years 2019 and 2020 at 1 of 16 U.S. hospitals of the Maternal-Fetal Medicine Units Network. The frequency of preterm birth for those who delivered before the onset of the COVID-19 pandemic (ie, in 2019) was compared with that of those who delivered after its onset (ie, in 2020). Interaction analyses were performed for …

Association Between Early Prostacyclin Therapy And Extracorporeal Life Support Use In Patients With Congenital Diaphragmatic Hernia, Akila B Ramaraj, Samuel E Rice-Townsend, Carrie L Foster, Delphine Yung, Emma O Jackson, Ashley H Ebanks, Matthew T Harting, Rebecca A Stark, Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).

OBJECTIVE: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first …

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. …

The Detrimental Role Of Angiotensin Receptor Agonistic Autoantibodies In Intrauterine Growth Restriction Seen In Preeclampsia, Monika M Safford, Doyle M Cummings, Jacqueline Halladay, James M Shikany, Joshua Richman, Suzanne Oparil, James Hollenberg, Alyssa Adams, Muna Anabtawi, Lynn Andreae, Elizabeth Baquero, Joanna Bryan, Debra Clark, Ethel Johnson, Erica Richman, Orysya Soroka, James Tillman, Andrea L Cherrington

Faculty, Staff and Student Publications

BACKGROUND: Impoverished African Americans (AA) with hypertension face poor health outcomes.

PURPOSE: To conduct a cluster-randomized trial testing two interventions, alone and in combination, to improve blood pressure (BP) control in AA with persistently uncontrolled hypertension.

METHODS: We engaged primary care practices serving rural Alabama and North Carolina residents, and in each practice we recruited approximately 25 AA adults with persistently uncontrolled hypertension (mean systolic BP >140 mmHg over the year prior to enrollment plus enrollment day BP assessed by research assistants ≥140/90 mmHg). Practices were randomized to peer coaching (PC), practice facilitation (PF), both PC and PF (PC + …

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 …

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, …

Evolving Antibiotic Resistance In Group B Streptococci Causing Invasive Infant Disease: 1970–2021, Elizabeth Marie Sabroske, Misu Ailin Sanson Iglesias, Marcia Rench, Trevor Moore, Hanna Harvey, Morven Edwards, Carol J Baker, Anthony R Flores

Faculty, Staff and Student Publications

BACKGROUND: We sought to define the frequency of antibiotic resistance over time in a collection of invasive GBS isolates derived from infant early-onset disease (EOD), late-onset disease (LOD), and late-late onset disease (LLOD).

METHODS: A multicenter retrospective review of infants born from 1970 to 2021 with GBS isolated from blood, cerebrospinal fluid, synovial fluid, cellulitis, or bone. All isolates were serotyped and antimicrobial susceptibility testing performed using disk diffusion.

RESULTS: The most common serotypes in our 2017 isolates were III (n = 1112, 55.1%), Ia (n = 445, 22%), Ib (n = 182, 9%) and II (n = 146, 7.2%). …

Clinicopathologic Features Of Therapy-Related Myeloid Neoplasms In Patients With Myeloma In The Era Of Novel Therapies, Fatima Zahra Jelloul, Andres E Quesada, Richard K Yang, Shaoying Li, Wei Wang, Jie Xu, Guilin Tang, C Cameron Yin, Hong Fang, Siba El Hussein, Joseph Khoury, Roland L Bassett, Guillermo Garcia-Manero, Elizabet E Manasanch, Robert Z Orlowski, Muzaffar H Qazilbash, Keyur P Patel, L Jeffrey Medeiros, Pei Lin

Faculty, Staff and Student Publications

The development of therapy-related myeloid neoplasms (t-MN) is a rare complication that can occur in myeloma patients treated primarily with novel therapies. To better understand t-MNs in this context, we reviewed 66 such patients and compared them with a control group of patients who developed t-MN after cytotoxic therapies for other malignancies. The study group included 50 men and 16 women, with a median age of 68 years (range, 48-86 years). Therapies included proteasome inhibitors, immunomodulatory agents, and high-dose melphalan-based autologous stem cell transplantation (HDM-ASCT) in 64 (97%), 65 (98.5%), and 64 (97%) patients, respectively; 29 (43.9%) patients were exposed …

Sedation And Analgesia For Reduction Of Pediatric Ileocolic Intussusception, Naveen Poonai, Daniel M Cohen, Doug Macdowell, Rakesh D Mistry, Santiago Mintegi, Simon Craig, Damian Roland, Michael Miller, Itai Shavit, Paediatric Emergency Research Networks (Pern) Paint Study Group;, Yvette Wang, Alan Nager, Theodore Heyming, Rebekah Burns, Indi Trehan, Matthew Lipshaw, Carmen Sulton, Joyce Li, Aderonke Ojo, Susan Kelly, Matthew Thornton, Kerry Caperell, Iluonose Amoni, Anna Abrams, Myto Duong, Muhammad Wassem, Adrienne Davis, Jocelyn Gravel, Evelyne Doyon Trottier, Neta Bar Am, Graham Thompson, Vikram Sabhaney, Garth Meckler, Rini Jain, Samina Ali, Silvia Bressan, Tiziana Zangardi, Giovanna Villa, Martina Giacalone, Michelle Seiler, Cyril Sahyoun, Fabrizio Romano, Zsolt Bognar, Szofia Hajosi-Kalcakosz, Lisa Amir, Said Hachimi-Idrissi, Zanda Pucuka, Astra Zviedre, Emilija Zeltina, Natalie Phillips, Meredith Borland, Sharon O'Brien, Jeanette Marchant, Amit Kochar, Shane George, Victoria Pennington, Mark Lyttle, Jen Browning, Anna Mcloughlin, Stuart Hartshorn, Chaman Urooj, Lucy Johnston, Emily Walton, Deepika Subrahmanyam Puthucode, Phil Peacock, James Conroy, Rafael Marañon, Silvia Garcia, Nuria Cahís, Amaia Cámara-Otegui, Arantxa Gomez, Maria Carbonero, Carlos Angelats-Romero, Adriana Yock-Corrales, Gabriela Hualde, Fabian Spigariol, Alex Donas, Cinthia Gübeli Linné, Alessia Rocchi, Alessia Pedrazzini, Giorgio Cozzi, Dino Barbi, Laura Baggio, Giovana La Fauci, Angela Mauro, Matthew Steimle, Danilo Buonsenso, Irma Ugalde, Gaby Nieva, Charlotte Harper, Idanna Sforzi, Shobhit Jain

Faculty, Staff and Student Publications

IMPORTANCE: Ileocolic intussusception is an important cause of intestinal obstruction in children. Reduction of ileocolic intussusception using air or fluid enema is the standard of care. This likely distressing procedure is usually performed without sedation or analgesia, but practice variation exists.

OBJECTIVE: To characterize the prevalence of opioid analgesia and sedation and assess their association with intestinal perforation and failed reduction.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reviewed medical records of children aged 4 to 48 months with attempted reduction of ileocolic intussusception at 86 pediatric tertiary care institutions in 14 countries from January 2017 to December 2019. Of …

Patient-Reported Bowel Function And Bowel-Related Quality Of Life After Pelvic Radiation For Rectal Adenocarcinoma: The Impact Of Radiation Fractionation And Surgical Resection, Michael K Rooney, Brian De, Kelsey Corrigan, Grace L Smith, Cullen Taniguchi, Bruce D Minsky, Ethan B Ludmir, Eugene J Koay, Prajnan Das, Albert C Koong, Oliver Peacock, George Chang, Y Nancy You, Van K Morris, Graciela Nogueras-González, Emma B Holliday

Faculty, Staff and Student Publications

INTRODUCTION: Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited.

METHODS: Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management.

RESULTS: Of 204 patients …

Clinical Implications Of Tumor-Based Next-Generation Sequencing In High-Grade Epithelial Ovarian Cancer, Katherine I Foster, Kenna R M Shaw, Jeff Jin, Shannon N Westin, Timothy A Yap, Deanna M Glassman, Amir A Jazaeri, Jose A Rauh-Hain, Sanghoon Lee, Bryan M Fellman, Zhenlin Ju, Yuexin Liu, Nicole D Fleming, Anil K Sood

Faculty, Staff and Student Publications

Background: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer.

Methods: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox …

Targeting Chemotherapy Resistance In Mesenchymal Triple-Negative Breast Cancer: A Phase Ii Trial Of Neoadjuvant Angiogenic And Mtor Inhibition With Chemotherapy, Nour Abuhadra, Ryan Sun, Roland L Bassett, Lei Huo, Jeffrey T Chang, Mediget Teshome, Alyson R Clayborn, Jason B White, Elizabeth E Ravenberg, Beatriz E Adrada, Rosalind P Candelaria, Wei Yang, Qingqing Ding, W Fraser Symmans, Banu Arun, Senthil Damodaran, Kimberly B Koenig, Rachel M Layman, Bora Lim, Jennifer K Litton, Alastair Thompson, Naoto T Ueno, Helen Piwnica-Worms, Gabriel N Hortobagyi, Vicente Valero, Debu Tripathy, Gaiane M Rauch, Stacy Moulder, Clinton Yam

Faculty, Staff and Student Publications

Background:: Metaplastic histology and mesenchymal differentiation have been associated with chemotherapy resistance in triple-negative breast cancer (TNBC). In the neoadjuvant setting, suboptimal on-treatment clinical response to chemotherapy is associated with low rates of pathological complete response (pCR). Given the previously demonstrated activity of pegylated liposomal doxorubicin, bevacizumab, and mTOR inhibition with temsirolimus (DAT) or everolimus (DAE) in metastatic, metaplastic TNBC, we conducted a phase II study of DAT/DAE as the second phase of neoadjuvant therapy in patients with metaplastic and/or mesenchymal TNBC experiencing suboptimal clinical response to neoadjuvant doxorubicin and cyclophosphamide (AC) (NCT02456857).

Patients and Methods:: Patients received …

Targeting Fatty Acid Reprogramming Suppresses Carm1-Expressing Ovarian Cancer, Simona Lombardi, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Heng Liu, Wei Zhou, Meenhard Herlyn, Jianhuang Lin, Rugang Zhang

Faculty, Staff and Student Publications

The arginine methyltransferase CARM1 exhibits high expression levels in several human cancers, with the trend also observed in ovarian cancer. However, therapeutic approaches targeting tumors that overexpress CARM1 have not been explored. Cancer cells exploit metabolic reprogramming such as fatty acids for their survival. Here we report that CARM1 promotes monounsaturated fatty acid synthesis and fatty acid reprogramming represents a metabolic vulnerability for CARM1-expressing ovarian cancer. CARM1 promotes the expression of genes encoding rate-limiting enzymes of de novo fatty acid metabolism such as acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN). In addition, CARM1 upregulates stearoyl-CoA desaturase 1 (SCD1) …

A Phase Ii Study Of Neoadjuvant Atezolizumab And Nab-Paclitaxel In Patients With Anthracycline-Resistant Early-Stage Triple-Negative Breast Cancer, Clinton Yam, Elizabeth A Mittendorf, Haven R Garber, Ryan Sun, Senthil Damodaran, Rashmi K Murthy, David Ramirez, Meghan Karuturi, Rachel M Layman, Nuhad Ibrahim, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Jason B White, Elizabeth Ravenberg, Alyson Clayborn, Qing Qing Ding, W Fraser Symmans, Sabitha Prabhakaran, Alastair M Thompson, Vicente Valero, Debu Tripathy, Lei Huo, Stacy L Moulder, Jennifer K Litton

Faculty, Staff and Student Publications

Purpose: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489).

Methods: Patients …