Life Sciences Commons^™

Dynamic Contrast-Enhanced Mri Processing Comparison For Distinguishing True Progression From Pseudoprogression In High-Grade Glioma, Ahmad Amer, Shehbaz Ansari, Apollo Krayyem, Suprateek Kundu, Swapnil Khose, Halyna Pokhylevych, Susana Calle, Chirag B Patel, Zixi Yang, Ho-Ling Anthony Liu, Jason M Johnson

Faculty, Staff and Student Publications

Background: Treatment-related changes may occur due to radiation and temozolomide in glioblastoma and can mimic tumor progression on conventional MRI. DCE-MRI enables quantification of the extent of blood-brain barrier (BBB) disruption, providing information about areas of suspicious postcontrast T1 enhancement. We compared DCE-MRI processing methods for distinguishing true disease progression from pseudoprogression in high-grade gliomas (HGGs).

Methods: We identified 110 patients with HGG treated with surgery and chemoradiation who underwent DCE-MRI to further interrogate areas of new/increasing enhancement. All patients had confirmatory surgery/biopsy with pathology-confirmed progression or pseudoprogression. Scans were performed at 3T and analyzed using nordicICE. The MCA, SSS, …

Hyalinization-Based Pathologic Response And Immune Infiltration Following Neoadjuvant Radiotherapy With Or Without Immune-Checkpoint Blockade In Localized Undifferentiated Pleomorphic Sarcoma, R S Traweek, M Zoghbi, R Lazcano, B M Cope, A J Bishop, A Farooqi, D Mitra, A K Yoder, B A Guadagnolo, D R Ingram, K Wani, D Shamsutdinova, A J Lazar, W-L Wang, C P Scally, E Z Keung, K E Torres, K K Hunt, R Ratan, J A Livingston, M S Nakazawa, D M Araujo, S Patel, V Ravi, A P Conley, M A Zarzour, N Somaiah, C L Roland, E F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Standard-of-care treatment of localized undifferentiated pleomorphic sarcoma (UPS) involves preoperative radiotherapy (RT) and surgery. Combination of RT with immune-checkpoint blockade (ICB) represents a promising new strategy.

METHODS: Our primary objective was to assess survival outcomes and pathologically documented response in patients receiving RT with or without ICB or chemotherapy.

RESULTS: In a retrospective cohort of 68 patients with primary or locally recurrent UPS who received neoadjuvant RT with or without ICB, the ICB group had greater tumor hyalinization than the non-ICB group (89% compared with 30%, P = 0.018). In the non-ICB group, 19/37 patients (51%) achieved hyalinization-based pathologic …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Pancreatic Neuroendocrine Neoplasm (Pnen) Cohort, Sandip Pravin Patel, Jillian Fisher, Young Kwang Chae, Luisa Solis Soto, Anup Kasi, Bhavana Konda, Mark Walshauser, Edwin Parra, Jiexin Zhang, Caroline Duault, Edgar Gonzalez-Kozlova, Ganiraju Manyam, Jianhua Zhang, Hong Chen, Dzifa Yawa Duose, Caddie Laberiano Fernandez, Raja Luthra, Gheath Al-Atrash, Seunghee Kim-Schulze, Holden T Maecker, Ignacio I Wistuba, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Christine M Magner, Helen X Chen, Elad Sharon, Megan Othus, Christopher W Ryan, Charles Blanke, Cara L Haymaker, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

Experimental design: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative …

Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators

Faculty, Staff and Student Publications

Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …

Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Edwin Parra, Lauren Byers, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker

Faculty, Staff and Student Publications

Tumor-initiated emergency granulopoiesis results in expansion of the circulating neutrophil compartment and neutrophil recruitment into the tumor microenvironment (TME), which may in turn promote tumor progression. Although an elevated circulating neutrophil-to-lymphocyte ratio (cNLR) has repeatedly been demonstrated to be an adverse prognostic factor in patients with non-small cell lung cancer (NSCLC), whether this neutrophil expansion in circulation reflects a similar relative neutrophil abundance in the TME remains unclear. We sought to characterize the relationships between cNLR and the intratumoral neutrophil-to-lymphocyte ratio (tNLR), between tNLR and proteogenomic and immune features of NSCLC tumors, and between tNLR and prognosis.We analyzed tNLR (transcriptomic …

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Rosa Maria Andres Ejarque, Giulia Maggioni, Alberto Termanini, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …

Blood-Based Proteomic Profiling Identifies Osmr As A Novel Biomarker Of Aml Outcomes, Patrick K Reville, Bofei Wang, Jennifer Marvin-Peek, Bin Yuan, Yu-An Kuo, Araceli Garza, Jessica Root, Wei Qiao, Andrea Arruda, Ivo Veletic, Yiwei Liu, Nicholas J Short, Courtney D Dinardo, Tapan M Kadia, Naval G Daver, Philip L Lorenzi, Koji Sasaki, Steven Kornblau, Mark D Minden, Farhad Ravandi, Hagop M Kantarjian, Hussein A Abbas

Faculty, Staff and Student Publications

Inflammation is increasingly recognized as a critical factor in acute myeloid leukemia (AML) pathogenesis. We performed blood-based proteomic profiling of 251 inflammatory proteins in 543 patients with newly diagnosed AML. Using a machine learning model, we derived an 8-protein prognostic score termed the leukemia inflammatory risk score (LIRS). Individual proteins were evaluated in multivariable Cox models, and model performance was assessed by cumulative concordance index. Findings were validated in internal and external cohorts across 2 institutions. Blood-based LIRS significantly outperformed the European LeukemiaNet 2022 risk model and was independently prognostic of overall survival after accounting for known clinical and molecular …

Azacitidine, Venetoclax, And Magrolimab In Newly Diagnosed And Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/Ii Study And Correlative Analysis, Naval Daver, Jayastu Senapati, Hagop M Kantarjian, Bofei Wang, Patrick K Reville, Sanam Loghavi, Musa Yilmaz, Courtney D Dinardo, Tapan M Kadia, Mhd Yousuf Yassouf, Abhishek Maiti, Sankalp Arora, Guillermo Montalban Bravo, Guilin Tang, Gautam Borthakur, Koji Sasaki, Naveen Pemmaraju, Joie Alvarez, Graciela M Nogueras Gonzalez, Jing Ning, Ghayas C Issa, Marina Konopleva, Michael Andreeff, Farhad Ravandi, Guillermo Garcia-Manero, Hussein A Abbas

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody directed against the macrophage checkpoint CD47 on myeloid leukemia cells that was preclinically synergistic with azacitidine-venetoclax, warranting further clinical evaluation.

Patients and methods: In this phase Ib/II study, the triplet combination of azacitidine, venetoclax, and magrolimab was evaluated in adult patients with first-line (ineligible for intensive chemotherapy) and relapsed/refractory acute myeloid leukemia. Azacitidine was dosed at 75 mg/m2 for 7 days, venetoclax at 400 mg/day for 28 days, and magrolimab (recommended phase II dose) as follows: 1 mg/kg dose on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Ranran Wu, Rahmah Ejaz, Hamid K Rudsari, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Time Dependency For Human Papillomavirus Circulating Tumor Dna Detection After Chemoradiation As A Prognostic Biomarker For Localized Anal Cancer, Van K Morris, Weihong Xiao, Kangyu Lin, Chi Wut Wong, Michael T Wotman, Emma B Holliday, Ryan W Huey, Sonal S Noticewala, Ethan B Ludmir, Alisha H Bent, Kaysia Ludford, Craig Messick, Eugene J Koay, Grace Smith, Tsuyoshi Konishi, Brian Bednarski, George J Chang, Albert C Koong, Y Nancy You, Prajnan Das, Maura L Gillison

Faculty, Staff and Student Publications

Purpose: Although detection of ctDNA weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Experimental design: Patients with stages I to III anal cancer treated with chemoradiation between December 2020 and March 2024 were evaluated for human papillomavirus (HPV) ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay, targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was …

Omitting Regional Nodal Irradiation After Response To Neoadjuvant Chemotherapy, Eleftherios P Mamounas, Hanna Bandos, Julia R White, Thomas B Julian, Atif J Khan, Simona F Shaitelman, Mylin A Torres, Frank A Vicini, Patricia A Ganz, Susan A Mccloskey, Peter C Lucas, Nilendu Gupta, X Allen Li, Beryl Mccormick, Benjamin Smith, Rahul D Tendulkar, Vivek S Kavadi, Koji Matsumoto, Samantha Andrews Seaward, William J Irvin, Jolinta Y Lin, Robert W Mutter, Thierry M Muanza, Jannifer Stromberg, Reshma Jagsi, Anna C Weiss, Walter J Curran, Norman Wolmark

Faculty, Staff and Student Publications

Background: The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

Methods: We evaluated whether regional nodal irradiation improves outcomes in patients with biopsy-proven, node-positive breast cancer who reach ypN0 status after neoadjuvant chemotherapy. Patients with breast cancer with a clinical stage of T1 to T3 (tumor size, ≤2 cm to >5 cm), N1, and M0 (indicating spread to one to three axillary lymph nodes but no distant …

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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. …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

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 …