Biomedical Informatics Commons^™

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

Outcomes After Palliative Radiation Therapy In Patients With Symptomatic Locoregionally Advanced Breast Cancer, Luisa E Jacomina, David M Swanson, Melissa P Mitchell, Wendy A Woodward, Benjamin D Smith, Karen E Hoffman, Chelain R Goodman, Haven R Garber, Susie X Sun, Timothy A Yap, Funda Meric-Bernstam, Isidora Y Arzu, Elizabeth S Bloom, Pamela J Schlembach, Eric A Strom, Michael C Stauder, Simona F Shaitelman

Faculty, Staff and Student Publications

Purpose: Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiation therapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined.

Methods and materials: This is a single institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were …

Impact Of Screening For Human Papillomavirus-Positive Oropharyngeal Cancers: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

Background: We estimated the impact of screening on morbidity and mortality of human papillomavirus (HPV)16-positive oropharyngeal cancer among US men aged 45-79 years.

Methods: We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed 4 progression speeds across cancer stages (very slow, slow, fast, and very fast) and 4 screening frequencies.

Results: Among US men aged 45-79 years in 2021 (n = 54 …

Association Of Sirt6 Expression With Risk Of Pneumonitis Induced By Radiotherapy In Cancer Patients, Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

Faculty, Staff and Student Publications

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Functional Vs Structural Cortical Deficit Pattern Biomarkers For Major Depressive Disorder, Peter Kochunov, Bhim M Adhikari, David Keator, Daniel Amen, Si Gao, Nicole R Karcher, Demetrio Labate, Robert Azencott, Yewen Huang, Hussain Syed, Hongjie Ke, Paul M Thompson, Danny J J Wang, Braxton D Mitchell, Jessica A Turner, Theo G M Van Erp, Neda Jahanshad, Yizhou Ma, Xiaoming Du, William Burroughs, Shuo Chen, Tianzhou Ma, Jair C Soares, L Elliot Hong

Faculty, Staff and Student Publications

Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

Objective: To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus …

Home-Based Transcranial Direct Current Stimulation For Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial And Open-Label Treatment Phases, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

Faculty, Staff and Student Publications

Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were …

The Burden Of Burnout: Understanding Its Prevalence And Organizational Drivers In Medical Physics, Deborah Schofield, C Lynn Chevalier, Laurence Court, William Harmsen, Akiva Turner

Faculty, Staff and Student Publications

Background: Burnout is a work-related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care.

Purpose: The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined.

Methods: The anonymous survey was distributed to 1962 full members of the American …

Implications Of Omitting Sentinel Lymph Node Biopsy On Adjuvant Decision Making For Patients With Small Breast Cancers, Kerollos Nashat Wanis, Melissa P Mitchell, Sharon H Giordano, Jennifer Keating Litton, Simona F Shaitelman, Nina Tamirisa, Isabelle Bedrosian, Wenli Dong, Yu Shen, Kelly K Hunt, Puneet Singh, Susie X Sun, Abigail S Caudle, Henry M Kuerer, Funda Meric-Bernstam, Rosa F Hwang, Taiwo Adesoye

Faculty, Staff and Student Publications

Background: Selective omission of sentinel lymph node biopsy (SLNB) in patients with early breast cancer limits surgical morbidity. Adoption of this strategy relies on multidisciplinary consensus. Understanding how SLNB omission influences guideline-based adjuvant treatment decisions, and the proportion of patients impacted, can help guide decision-making.

Patients and methods: Data from the National Cancer Database (2018-2020) was used to estimate the proportions of patients with cT1N0 hormone receptor-positive breast cancer for whom adjuvant chemotherapy, CDK4/6 inhibitor therapy, and regional nodal irradiation decisions would be impacted by the absence of lymph node pathology if national treatment guidelines were followed. Because OncotypeDX score …

Encoding 3d Information In 2d Feature Maps For Brain Ct-Angiography, Uma M Lal-Trehan Estrada, Sunil Sheth, Arnau Oliver, Xavier Lladó, Luca Giancardo

Faculty, Staff and Student Publications

We propose learnable 3D pooling (L3P), a CNN module designed to compress 3D information into 2D feature maps using anisotropic convolutions and unidirectional max pooling. Specifically, we used L3P followed by a 2D network to generate predictions from 3D brain CT-Angiography (CTA) in the context of large vessel occlusion (LVO). To further demonstrate its versatility, we extended its application to 3D brain MRI analysis for brain age prediction. First, we designed an experiment to classify the LVO-affected hemisphere (left or right), projecting the input CTA into the sagittal plane, which allowed to assess the ability of L3P to encode the …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Kyle B Spier, Natalie A West, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Methylation Risk Score Of C-Reactive Protein Associates Sleep Health With Related Health Outcomes, Ziqing Wang, Danielle A Wallace, Brian W Spitzer, Tianyi Huang, Kent D Taylor, Jerome I Rotter, Stephen S Rich, Peter Y Liu, Martha L Daviglus, Lifang Hou, Alberto R Ramos, Sonya Kaur, J Peter Durda, Hector M González, Myriam Fornage, Susan Redline, Carmen R Isasi, Tamar Sofer

Faculty, Staff and Student Publications

C-reactive protein (CRP) reflects inflammation status and is linked to poor sleep, metabolic and cardiovascular health. Methylation (MRS) and polygenic risk scores (PRS) reflect long-term systemic inflammation, and genetically-determined CRP, respectively. To refine understanding of inflammation-linked sleep and health outcomes, we construct PRS-CRPs using GWAS summary statistics and a previously-developed MRS-CRP in the Hispanic Community Health Study/Study of Latinos. Via survey-weighted linear regression, we estimate associations between blood-, PRS-, and MRS-CRP, with multiple sleep and health outcomes (n = 2217). MRS-CRP and PRS-CRPs are associated with increasing blood-CRP level by 43% and 23% per standard deviation. MRS-CRP is associated with …

The Impact Of Breast Radiotherapy On The Tumor Genome And Immune Ecosystem, Aislyn Schalck, Tuan Tran, Jianzhuo Li, Emi Sei, Shanshan Bai, Min Hu, Jerome Lin, Scott J Bright, Samuel Reddick, Fei Yang, Harsh Batra, Alejandro Contreras, Maria Gabriela Raso, Michael C Stauder, Karen E Hoffman, Jay P Reddy, Kevin T Nead, Benjamin D Smith, Gabriel O Sawakuchi, Wendy A Woodward, Stephanie S Watowich, Jennifer K Litton, Isabelle Bedrosian, Elizabeth A Mittendorf, Huong Le-Petross, Nicholas E Navin, Simona F Shaitelman

Faculty, Staff and Student Publications

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. …

Epigenome-Wide Dna Methylation Association Study Of Chip Provides Insight Into Perturbed Gene Regulation, Sara Kirmani, Tianxiao Huan, Joseph C Van Amburg, Roby Joehanes, Md Mesbah Uddin, Ngoc Quynh H Nguyen, Bing Yu, Jennifer A Brody, Myriam Fornage, Jan Bressler, Nona Sotoodehnia, David A Ong, Fabio Puddu, James S Floyd, Christie M Ballantyne, Bruce M Psaty, Laura M Raffield, Pradeep Natarajan, Karen N Conneely, Joshua S Weinstock, April P Carson, Leslie A Lange, Kendra Ferrier, Nancy L Heard-Costa, Joanne Murabito, Alexander G Bick, Daniel Levy

Faculty, Staff and Student Publications

With age, hematopoietic stem cells can acquire somatic mutations in leukemogenic genes that confer a proliferative advantage in a phenomenon termed CHIP. How these mutations result in increased risk for numerous age-related diseases remains poorly understood. We conduct a multiracial meta-analysis of EWAS of CHIP in the Framingham Heart Study, Jackson Heart Study, Cardiovascular Health Study, and Atherosclerosis Risk in Communities cohorts (N = 8196) to elucidate the molecular mechanisms underlying CHIP and illuminate how these changes influence cardiovascular disease risk. We functionally validate the EWAS findings using human hematopoietic stem cell models of CHIP. We then use expression quantitative …

Neoadjuvant With Low-Dose Radiotherapy, Tislelizumab, Albumin-Bound Paclitaxel, And Cisplatin For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma: Phase Ii Single-Arm Trial, Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Lizhong Liang, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhijie Liu, Wen Jiang

Faculty, Staff and Student Publications

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

Allogeneic Chimeric Antigen Receptor T-Cell Products Cemacabtagene Ansegedleucel/Allo-501 In Relapsed/Refractory Large B-Cell Lymphoma: Phase I Experience From The Alpha2/Alpha Clinical Studies, Frederick L Locke, Javier L Munoz, Michael T Tees, Lazaros J Lekakis, Sven De Vos, Rajneesh Nath, Don A Stevens, Shahbaz A Malik, Geoffrey P Shouse, Mehdi Hamadani, Olalekan O Oluwole, Miguel-Angel Perales, David B Miklos, Paul W Fisher, Amy Feng, Lynn Navale, John B Le Gall, Sattva S Neelapu

Faculty, Staff and Student Publications

Purpose: Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T-cell products may improve access to treatment versus autologous ones. We report the phase I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naïve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).

Methods: In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naïve patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen-unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m2 once daily), cyclophosphamide (300 or 500 mg/m2 …

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Graeme Segal, Stephanie Novak, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

Longitudinal Profiling Of Circulating Tumor Dna Reveals The Evolutionary Dynamics Of Metastatic Prostate Cancer During Serial Therapy, Yuehui Zhao, Naveen Ramesh, Ping Xu, Emi Sei, Min Hu, Shanshan Bai, Patricia Troncoso, Ana M Aparicio, Christopher J Logothetis, Paul G Corn, Nicholas E Navin, Amado J Zurita

Faculty, Staff and Student Publications

Treatment decisions in metastatic castration-resistant prostate cancer are mostly guided by clinical variables, but efforts to molecularly monitor the disease remain hampered by challenges in acquiring tumor tissue repeatedly. In this study, we simultaneously profiled the genome copy number and exome in longitudinal plasma circulating tumor DNA (ctDNA) acquired before, during, and upon progression to serial treatments with androgen signaling inhibitors and taxane chemotherapy from 60 patients with metastatic castration-resistant prostate cancer (2-10 samples per patient). The genomic data were used to delineate the clonal substructure and evolutionary dynamics of each patient, and an evolutionary dynamic index was developed to …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Elena Garralda, Antoine Italiano, Damian T Rieke, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Genomic Characterization Of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features In Black Individuals, Katherine A Lawson-Michod, Jeffrey R Marks, Lindsay J Collin, David A Nix, Natalie R Davidson, Chad D Huff, Yao Yu, Aaron Atkinson, Courtney E Johnson, Lucas A Salas, Lauren C Peres, Casey S Greene, Joellen M Schildkraut, Jennifer A Doherty

Faculty, Staff and Student Publications

Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas …

The Association Of Discrimination, Inflammation, And Coping Style On Self-Rated Health Among South Asian Individuals In The Masala Study, Raji Pillai, Sahiti Myneni, Constance M Johnson, Nilay S Shah, Alka M Kanaya, Jennifer E S Beauchamp

Faculty, Staff and Student Publications

Objectives: South Asian individuals (SAs) may have heightened levels of inflammatory markers, such as C reactive protein (CRP), Tumor Necrosis Factor-α (TNF-α), leptin, and resistin, and decreased levels of anti-inflammatory adiponectin, contributing to higher cardiovascular disease (CVD) incidence. Social determinants of health, like discrimination, are also associated with risks for CVD in SAs. This study examined the associations between discrimination and inflammation and whether coping styles moderated the association between discrimination and self-rated health (SRH) among SAs in the United States.

Design: Secondary analysis of data obtained from 1164 SAs (mean age = 57 years, SD = 9.4, 48% women) …

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

Faculty, Staff and Student Publications

Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Phase Ii Trial Of Atezolizumab And Bevacizumab For Treatment Of Hpv-Positive Unresectable Or Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Suyu Liu, Kangyu Lin, Haifeng Zhu, Seema Prasad, Armeen Mahvash, Priya Bhosale, Baohua Sun, Edwin R Parra, Ignacio Wistuba, Arjun Peddireddy, James Yao, Julia Mendoza-Perez, Mark Knafl, Scott E Woodman, Cathy Eng, Daniel Halperin

Faculty, Staff and Student Publications

Purpose: Anti-PD-L1 antibodies are associated with responses in < 25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Patients and methods: For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test.

Results: Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2-32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6-not …

Race And Clinical Outcomes In Hormone Receptor-Positive, Her2-Negative, Node-Positive Breast Cancer In The Randomized Rxponder Trial, Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky

Faculty, Staff and Student Publications

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 …

Impact Of Comorbidities On The Mortality Benefits Of Lung Cancer Screening: A Post-Hoc Analysis Of The Plco And Nlst Trials, Sebastien Gendarme, Ehsan Irajizad, James P Long, Johannes F Fahrmann, Jennifer B Dennison, Seyyed Mahmood Ghasemi, Rongzhang Dou, Robert J Volk, Rafael Meza, Iakovos Toumazis, Florence Canoui-Poitrine, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Objectives: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.

Methods: We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile …