Medical Specialties Commons^™

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

Faculty, Staff and Student Publications

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

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

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

Author Correction: An Atlas Of Epithelial Cell States And Plasticity In Lung Adenocarcinoma, Guangchun Han, Ansam Sinjab, Zahraa Rahal, Anne M Lynch, Warapen Treekitkarnmongkol, Yuejiang Liu, Alejandra G Serrano, Jiping Feng, Ke Liang, Khaja Khan, Wei Lu, Sharia D Hernandez, Yunhe Liu, Xuanye Cao, Enyu Dai, Guangsheng Pei, Jian Hu, Camille Abaya, Lorena I Gomez-Bolanos, Fuduan Peng, Minyue Chen, Edwin R Parra, Tina Cascone, Boris Sepesi, Seyed Javad Moghaddam, Paul Scheet, Marcelo V Negrao, John V Heymach, Mingyao Li, Steven M Dubinett, Christopher S Stevenson, Avrum E Spira, Junya Fujimoto, Luisa M Solis, Ignacio I Wistuba, Jichao Chen, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

No abstract provided.

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

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

Faculty, Staff and Student Publications

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

Surgical Outcomes After Chemotherapy Plus Nivolumab And Chemotherapy Plus Nivolumab And Ipilimumab In Patients With Non-Small Cell Lung Cancer, Hope Feldman, Boris Sepesi, Cheuk H Leung, Heather Lin, Annikka Weissferdt, Apar Pataer, William N William, Garrett L Walsh, David C Rice, Jack A Roth, Reza J Mehran, Wayne L Hofstetter, Mara B Antonoff, Ravi Rajaram, Don L Gibbons, J Jack Lee, John V Heymach, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone

Faculty, Staff and Student Publications

Objective: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab.

Methods: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab …

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

Faculty, Staff and Student Publications

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

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

Cytogenetic And Molecular Associations With Outcomes In Higher-Risk Myelodysplastic Syndromes Treated With Hypomethylating Agents Plus Venetoclax, Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M Kadia, Gautam Borthakur, Courtney D Dinardo, Naval G Daver, Elias J Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood.

Experimental design: We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations …

Analysis Of Microbiome Data, Christine B Peterson, Satabdi Saha, Kim-Anh Do

Faculty, Staff and Student Publications

The microbiome represents a hidden world of tiny organisms populating not only our surroundings but also our own bodies. By enabling comprehensive profiling of these invisible creatures, modern genomic sequencing tools have given us an unprecedented ability to characterize these populations and uncover their outsize impact on our environment and health. Statistical analysis of microbiome data is critical to infer patterns from the observed abundances. The application and development of analytical methods in this area require careful consideration of the unique aspects of microbiome profiles. We begin this review with a brief overview of microbiome data collection and processing and …

Prognostic Value Of Tumor Volume Doubling Time In Lung-Metastatic Adenoid Cystic Carcinoma, Eduardo A Dal Lago, Luana G Sousa, Zixi Yang, Camilla O Hoff, Flavia Bonini, Matthew Sawyer, Kaiwen Wang, Whitney Lewis, Kareem A Wahid, Ehab Y Hanna, Adel El-Naggar, Clifton D Fuller, Suprateek Kundu, Myrna Godoy, Renata Ferrarotto

Faculty, Staff and Student Publications

Objectives: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT).

Methods: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), …

Exploring Ferroptosis-Inducing Therapies For Cancer Treatment: Challenges And Opportunities, Guang Lei, Boyi Gan

Faculty, Staff and Student Publications

Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis-an iron-dependent regulated cell death triggered by lipid peroxide accumulation-has gained prominence in cancer research in recent years. Ferroptosis-inducing therapies hold promise for overcoming resistance encountered with conventional treatments. However, challenges, including the lack of distinctive ferroptosis markers and the intricate role of ferroptosis within the tumor microenvironment, currently hinder the clinical translation of these therapies. This perspective article critically outlines these hurdles and highlights …

Predicting Recurrence-Free And Overall Survival For Patients With Stage Ii Melanoma: The Mia Calculator, Alexander H R Varey, Isabel Li, Mary-Ann El Sharouni, Julie Simon, Aikaterini Dedeilia, Sydney Ch'ng, Robyn P M Saw, Andrew J Spillane, Kerwin F Shannon, Thomas E Pennington, Michael Rtshiladze, Jonathan R Stretch, Omgo E Nieweg, Alexander Van Akkooi, Ryan J Sullivan, Genevieve M Boland, Jeffrey E Gershenwald, Paul J Van Diest, Richard A Scolyer, Georgina V Long, John F Thompson, Serigne N Lo

Faculty, Staff and Student Publications

Purpose: Improvements in recurrence-free survival (RFS) were demonstrated in two recent randomized trials for patients with sentinel node (SN)-negative stage IIB or IIC melanoma receiving adjuvant systemic therapy (pembrolizumab/nivolumab). However, adverse events also occurred. Accurate individualized prognostic estimates of RFS and overall survival (OS) would allow patients to more accurately weigh the risks and benefits of adjuvant therapy. Since the current American Joint Committee on Cancer eighth edition (AJCC-8) melanoma staging system focuses on melanoma-specific survival, we developed a multivariable risk prediction calculator that provides estimates of 5- and 10-year RFS and OS for these patients.

Methods: Data were extracted …

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

Databases reviewed: PubMed, Cochrane Library, and Embase.

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

Results: The …

Developing Deep Learning-Based Strategies To Predict The Risk Of Hepatocellular Carcinoma Among Patients With Nonalcoholic Fatty Liver Disease From Electronic Health Records, Zhao Li, Lan Lan, Yujia Zhou, Ruoxing Li, Kenneth D Chavin, Hua Xu, Liang Li, David J H Shih, W Jim Zheng

Faculty, Staff and Student Publications

OBJECTIVE: The accuracy of deep learning models for many disease prediction problems is affected by time-varying covariates, rare incidence, covariate imbalance and delayed diagnosis when using structured electronic health records data. The situation is further exasperated when predicting the risk of one disease on condition of another disease, such as the hepatocellular carcinoma risk among patients with nonalcoholic fatty liver disease due to slow, chronic progression, the scarce of data with both disease conditions and the sex bias of the diseases. The goal of this study is to investigate the extent to which the aforementioned issues influence deep learning performance, …

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

Faculty, Staff and Student Publications

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

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

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

Early Elevations Of Ras Protein Level And Activity Are Critical For The Development Of Pdac In The Context Of Inflammation, Jianjia Ma, Fanghua Gong, Eunice Kim, James Xianxing Du, Cindy Leung, Qingchun Song, Craig D Logsdon, Yongde Luo, Xiaokun Li, Weiqin Lu

Faculty, Staff and Student Publications

The KRASG12D mutation was believed to be locked in a GTP-bound form, rendering it fully active. However, recent studies have indicated that the presence of mutant KRAS alone is insufficient; it requires additional activation through inflammatory stimuli to effectively drive the development of pancreatic ductal adenocarcinoma (PDAC). It remains unclear to what extent RAS activation occurs during the development of PDAC in the context of inflammation. Here, in a mouse model with the concurrent expression of KrasG12D/+ and inflammation mediator IKK2 in pancreatic acinar cells, we showed that, compared to KRASG12D alone, the cooperative interaction between KRASG12D and IKK2 rapidly …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Definitive Single Fraction Spine Stereotactic Radiosurgery For Metastatic Sarcoma: Simultaneous Integrated Boost Is Associated With High Tumor Control And Low Vertebral Fracture Risk, Mihir D Shanker, Adriana P Cavazos, Jing Li, Thomas H Beckham, Debra N Yeboa, Chenyang Wang, Mary Frances Mcaleer, Tina Marie Briere, Behrang Amini, Claudio E Tatsui, Robert Y North, Christopher A Alvarez-Breckenridge, Phillip Cem Cezayirli, Laurence D Rhines, Amol J Ghia, Andrew J Bishop

Faculty, Staff and Student Publications

Introduction: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS).

Materials and methods: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective …

Bone Mimetic Environments Support Engineering, Propagation, And Analysis Of Therapeutic Response Of Patient-Derived Cells, Ex Vivo And In Vivo, Claudia Paindelli, Vanessa Parietti, Sergio Barrios, Peter Shepherd, Tianhong Pan, Wei-Lien Wang, Robert L Satcher, Christopher J Logothetis, Nora Navone, Matthew T Campbell, Antonios G Mikos, Eleonora Dondossola

Faculty, Staff and Student Publications

Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated …

Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-To-Neuron Transmission, Chan Chen, Ramhari Kumbhar, Hu Wang, Xiuli Yang, Kundlik Gadhave, Cyrus Rastegar, Yasuyoshi Kimura, Adam Behensky, Sumasri Kotha, Grace Kuo, Sruthi Katakam, Deok Jeong, Liang Wang, Anthony Wang, Rong Chen, Shu Zhang, Lingtao Jin, Creg J Workman, Dario A A Vignali, Olga Pletinkova, Hongpeng Jia, Weiyi Peng, David W Nauen, Philip C Wong, Javier Redding-Ochoa, Juan C Troncoso, Mingyao Ying, Valina L Dawson, Ted M Dawson, Xiaobo Mao

Faculty, Staff and Student Publications

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it …

Targetable Genetic Abnormalities In Patients With Acute Myeloblastic Leukemia Across Age Groups, Alex Bataller, Courtney D Dinardo, Alexandre Bazinet, Naval G Daver, Abhishek Maiti, Gautam Borthakur, Nicholas Short, Koji Sasaki, Elias J Jabbour, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Guillermo Montalban-Bravo, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Incidence of potential targetable genetic abnormalities by age in AML.

Dose-Dense Mini-Hyper-Cvd, Inotuzumab Ozogamicin And Blinatumomab Achieves Rapid Mrd-Negativity In Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Trevor Jamison, Shilpa Paul, Branko Cuglievan, David Mccall, Amber Gibson, Nitin Jain, Fadi G Haddad, Lewis F Nasr, Kayleigh R Marx, Caitlin Rausch, J Michael Savoy, Rebecca Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD …

Chromatin Remodeling In Patient-Derived Colorectal Cancer Models, Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar, Shree Bose, Nicholas Giroux, Shengli Ding, Lihua Wang, Jorge Prado Balcazar, Qiang Huang, Pasupathi Sundaramoorthy, Rui Xi, Shannon Jones Mccall, Zhaohui Wang, Chongming Jiang, Yubin Kang, Scott Kopetz, Gregory E Crawford, Steven M Lipkin, Xiao-Fan Wang, Hans Clevers, David Hsu, Xiling Shen

Faculty, Staff and Student Publications

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors …

Disease Progression, Survival, And Molecular Disparities In Black And White Patients With Endometrioid Endometrial Carcinoma In Real-World Registries And Gog/Nrg Oncology Randomized Phase Iii Clinical Trials, Zachary A Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T Phippen, Christopher M Tarney, Erica R Hope, Stuart S Winkler, Suzanne Jokajtys, Calen W Kucera, John K Chan, Michael T Richardson, Daniel S Kapp, Chad A Hamilton, Charles A Leath, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Angeles Alvarez Secord, Casey M Cosgrove, Matthew A Powell, Ann Klopp, Joan L Walker, Gini F Fleming, Nicholas W Bateman, Thomas P Conrads, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) …

Normal Risk Ovarian Screening Study: 21-Year Update, Chae Young Han, Karen H Lu, Gwen Corrigan, Alexandra Perez, Sharlene D Kohring, Joseph Celestino, Deepak Bedi, Enrique Bedia, Therese Bevers, David Boruta, Matthew Carlson, Laura Holman, Leroy Leeds, Cara Mathews, Georgia Mccann, Richard G Moore, Matthew Schlumbrecht, Brian Slomovitz, Dan Tobias, Yvette Williams-Brown, Michael W Bevers, Jinsong Liu, Terrie G Gornet, Beverly C Handy, Zhen Lu, Jacob S Bedia, Steven J Skates, Robert C Bast

Faculty, Staff and Student Publications

Purpose: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

Methods: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and < 1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

Results: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 …

Histologic And Genomic Analysis Of Conjunctival Scc In African And American Cohorts Reveal Uv Light And Hpv Signatures And High Tumor Mutation Burden, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Oded Sagiv, Curtis R Pickering, Neil Gross, Jing Ning, Melisachew M Yeshi, Yonas Mitku, Michael T Tetzlaff, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies.

Methods: We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared …

Seamark: Phase Ii Study Of First-Line Encorafenib And Cetuximab Plus Pembrolizumab For Msi-H/Dmmr Brafv600e-Mutant Mcrc, Elena Elez, Scott Kopetz, Josep Tabernero, Tanios Bekaii-Saab, Julien Taieb, Takayuki Yoshino, Gulam Manji, Kathrine Fernandez, Antonello Abbattista, Xiaosong Zhang, Van K Morris

Faculty, Staff and Student Publications

Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination …

Dietary Magnesium Replacement For Prevention Of Hypomagnesemia In Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy, Wenli Liu, Larissa Meyer, Meroë Morse, Yisheng Li, Juhee Song, Rosalinda Engle, Gabriel Lopez, Santhosshi Narayanan, Pamela T Soliman, Lois Ramondetta, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Purpose: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment.

Materials and methods: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined …