Medical Specialties Commons^™

Author Correction: Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies

Faculty, Staff and Student Publications

No abstract provided.

A Bayesian Quasi-Likelihood Design For Identifying The Minimum Effective Dose And Maximum Utility Dose In Dose-Ranging Studies, Feng Tian, Ruitao Lin, Li Wang, Ying Yuan

Faculty, Staff and Student Publications

Most existing dose-ranging study designs focus on assessing the dose-efficacy relationship and identifying the minimum effective dose. There is an increasing interest in optimizing the dose based on the benefit-risk tradeoff. We propose a Bayesian quasi-likelihood dose-ranging design that jointly considers safety and efficacy to simultaneously identify the minimum effective dose and the maximum utility dose to optimize the benefit-risk tradeoff. The binary toxicity endpoint is modeled using a beta-binomial model. The efficacy endpoint is modeled using the quasi-likelihood approach to accommodate various types of data (e.g. binary, ordinal or continuous) without imposing any parametric assumptions on the dose-response curve. …

Comparative Analysis Of Brain Language Templates With Primary Language Areas Detected From Presurgical Fmri Of Brain Tumor Patients, Jina Lee, Vinodh A Kumar, Jian Ming Teo, Rami W Eldaya, Ping Hou, Kyle R Noll, Sherise D Ferguson, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

INTRODUCTION: Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients.

METHODS: Four language templates (A-D) based on anatomy, task-based fMRI, resting-state fMRI, and meta-analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by …

Salpingectomy For Ovarian Cancer Prevention: Video Education For The Surgeon, Emily Macarthur, Kara Long Roche, Joseph Sakran, Sunil H Patel, Peter Najjar, Karen H Lu, Megan Gornet, Anja S Frost, Meghan Walrath, Tom Bauer, Gyyong Oh, Rebecca Stone

Faculty, Staff and Student Publications

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on …

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma\, Angela E Alnemri, Sruti Tekumalla, Annie E Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David M Cognetti, Joseph M Curry, Athanassios Argiris, Alban Linnenbach, Andrew P South, Larry A Harshyne, Jennifer M Johnson, Adam J Luginbuhl

Faculty, Staff and Student Publications

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

A Phase I Study Of Tak-659 And Paclitaxel In Patients With Taxane-Refractory Advanced Solid Tumors, M A Gouda, J Shunyakova, A Naing, E Dumbrava, D S Hong, Y Yuan, P Yang, A Myers, Y Liang, J Peng, D Karp, A M Tsimberidou, J Rodon, T A Yap, S A Piha-Paul, F Meric-Bernstam, S Fu

Faculty, Staff and Student Publications

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.

PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients …

Impact Of Knockout Of Dual-Specificity Protein Phosphatase 5 On Structural And Mechanical Properties Of Rat Middle Cerebral Arteries: Implications For Vascular Aging, Chengyun Tang, Huawei Zhang, Jane J Border, Yedan Liu, Xing Fang, Joshua R Jefferson, Andrew Gregory, Claire Johnson, Tae Jin Lee, Shan Bai, Ashok Sharma, Seung Min Shin, Hongwei Yu, Richard J Roman, Fan Fan

Faculty, Staff and Student Publications

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and …

Duration Of Androgen Deprivation Therapy With Postoperative Radiotherapy For Prostate Cancer: A Comparison Of Long-Course Versus Short-Course Androgen Deprivation Therapy In The Radicals-Hd Randomised Trial, Chris C Parker, Howard Kynaston, Adrian D Cook, Noel W Clarke, Charles N Catton, William R Cross, Peter M Petersen, Rajendra A Persad, Cheryl A Pugh, Fred Saad, John Logue, Heather Payne, Lorna C Bower, Chris Brawley, Mary Rauchenberger, Maroie Barkati, David M Bottomley, Klaus Brasso, Hans T Chung, Peter W M Chung, Ruth Conroy, Alison Falconer, Vicky Ford, Chee L Goh, Catherine M Heath, Nicholas D James, Charmaine Kim-Sing, Ravi Kodavatiganti, Shawn C Malone, Stephen L Morris, Abdenour Nabid, Aldrich D Ong, Rakesh Raman, Sree Rodda, Paula Wells, Jane Worlding, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes

Faculty, Staff and Student Publications

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.

METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT …

From Pre-Clinical To Translational Brain Metastasis Research: Current Challenges And Emerging Opportunities, Emilija Aleksandrovic, Siyuan Zhang, Dihua Yu

Faculty, Staff and Student Publications

Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical interventions have remained elusive. The heterogeneous nature of the primary tumor of origin, complications in drug delivery across the blood-brain barrier, and the distinct microenvironment collectively pose formidable clinical challenges in developing new treatments for patients with brain metastasis. Although current preclinical models have deepened our basic understanding of the disease, much of the existing research on brain metastasis has employed a reductionist approach. This approach, which often relies on either in vitro systems or in …

Lymphovenous Anastomosis For The External And Internal Types Of Head And Neck Lymphedema: A Case Series And Preliminary Clinical Results, Ying-Sheng Lin, Chia-Ju Liu, Chen-Han Chou

Faculty, Staff and Student Publications

BACKGROUND: Head and neck lymphedema (HNL), including external and internal types, could be a possible consequence for patients who have received neck dissection and radiotherapy for head and neck cancer. Initially, the common presentations are heaviness or tightness, followed by swelling in appearance, or difficulty speaking and swallowing in internal edema cases. Lymphovenous anastomosis (LVA) is an established approach to treat extremity lymphedema. We hereby present our preliminary experience in using LVA to treat HNL.

METHODS: Between March 2021 and January 2024, six patients with HNL were treated with LVA via a preauricular or submandibular incision of the obstructed side. …

Targeting Sinonasal Undifferentiated Carcinoma With A Combinatory Immunotherapy Approach, Austin T K Hoke, Yoko Takahashi, Michelle R Padget, Javier Gomez, Moran Amit, Jared Burks, Diana Bell, Tongxin Xie, Patrick Soon-Shiong, James W Hodge, Ehab Y Hanna, Nyall R London

Faculty, Staff and Student Publications

PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME).

EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed.

RESULTS: Anti-PD-L1 blockade enhanced NK …

Genetic Evidence For Functional Diversification Of Gram-Negative Intermembrane Phospholipid Transporters, Ashutosh K Rai, Katsuhiro Sawasato, Haley C Bennett, Anastasiia Kozlova, Genevieve C Sparagna, Mikhail Bogdanov, Angela M Mitchell

Faculty, Staff and Student Publications

The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. It remains unclear whether these functions are related to phospholipid metabolism. We investigated a synthetic cold sensitivity caused by deletion of fadR, a transcriptional regulator …

Characteristics And Outcomes Of Acute Myeloid Leukaemia Patients With Baseline Cd7 Expression, Wei-Ying Jen, Koji Sasaki, Sanam Loghavi, Sa A Wang, Wei Qiao, Gautam Borthakur, Farhad Ravandi, Tapan M Kadia, Ghayas C Issa, Nicholas J Short, Musa Yilmaz, Naval G Daver, Courtney D Dinardo

Faculty, Staff and Student Publications

Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7-15.9] vs. 19.0 months [95% CI, 16.1-23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability …

Ivosidenib Significantly Reduces Triazole Levels In Patients With Acute Myeloid Leukemia And Myelodysplastic Syndrome, Ashley Dinh, J Michael Savoy, Dimitrios P Kontoyiannis, Koichi Takahashi, Ghayas C Issa, Hagop M Kantarjian, Courtney D Dinardo, Caitlin R Rausch

Faculty, Staff and Student Publications

Background: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations. Although posaconazole is a substrate of P-glycoprotein, it is metabolized primarily via UDP glucuronidation; thus, the impact of ivosidenib on posaconazole exposure is unknown.

Methods: Patients treated with ivosidenib and concomitant triazole with at least one …

Outcome Of Patients With Relapsed Acute Promyelocytic Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney D Dinardo, Musa Yilmaz, Nicholas Short, Elias Jabbour, Keyur P Patel, Sanam Loghavi, Sherry Pierce, Gautam Borthakur, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The outcome of patients with acute promyelocytic leukemia (APL) has improved significantly since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as APL therapies. The optimal therapy for APL relapse is believed to require autologous or allogeneic stem cell transplantation (SCT) based on historical experience.

Study aims: To evaluate the outcome of patients with relapsed APL before and after the era of ATRA-ATO.

Patients and methods: We reviewed 61 patients with relapsed APL treated from November 1991 to June 2023; 31 patients (51%) received modern therapy with the combination of ATRA and ATO with and without …

Germline Predisposition In Hematologic Malignancies: Testing, Management, And Implications, Lucy A Godley, Courtney D Dinardo, Kelly Bolton

Faculty, Staff and Student Publications

Although numerous barriers for clinical germline cancer predisposition testing exist, the increasing recognition of deleterious germline DNA variants contributing to myeloid malignancy risk is yielding steady improvements in referrals for testing and testing availability. Many germline predisposition alleles are common in populations, and the increasing number of recognized disorders makes inherited myeloid malignancy risk an entity worthy of consideration for all patients regardless of age at diagnosis. Germline testing is facilitated by obtaining DNA from cultured skin fibroblasts or hair bulbs, and cascade testing is easily performed via buccal swab, saliva, or blood. Increasingly as diagnostic criteria and clinical management …

Plasmacytoid Urothelial Carcinoma Of The Urinary Bladder-A Clinicopathological And Molecular Analysis Of 52 Cases, Lan Zheng, Hui Chen, Jianping Zhao, Sinchita Roy-Chowdhuri, Ashish M Kamat, Omar Alhalabi, Jianjun Gao, Arlene Siefker-Radtke, Donna E Hansel, Bogdan Czerniak, Charles C Guo

Faculty, Staff and Student Publications

Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41-91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5-100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n …

Determination Of Quality Of Life-Related Health Utilities For Surgical Complications In Ovarian Cancer, Rudy S Suidan, Charlotte C Sun, Amy K Schneider, Karen H Lu, Sharon H Giordano, Larissa A Meyer

Faculty, Staff and Student Publications

Objective: To assess the health state utilities of ovarian cancer patients, clinicians, and non-cancer controls regarding surgical complications in ovarian cancer.

Methods: Utilities for 14 surgical complications were assessed from patients with recently diagnosed or recurrent ovarian cancer, clinicians, and non-cancer controls using the visual analog scale (VAS) and time trade-off (TTO) methods. Health state utilities were converted to a 0-to-1 scale, where 0 represents the least favorable outcome and 1 represents the most favorable outcome.

Results: Fifty patients, 50 clinicians, and 50 controls participated. Median VAS scores were lower than TTO scores across all groups (p < 0.01). Patients viewed 'bleeding requiring transfusion' most favorably (VAS utility 0.75), followed in order by less favorable utility scores for hernia, thromboembolism, pleural effusion, abscess, ileus/bowel obstruction, wound infection, bowel obstruction requiring surgery, anastomotic leak requiring drain, temporary ostomy, anastomotic leak requiring surgery, genito-urinary fistula, permanent ostomy, and genito-intestinal fistula (VAS utility 0.2). Overall, clinicians perceived complications more favorably than patients by VAS (overall utility score 0.49 vs 0.43, p < 0.01), but not by the TTO. There were no differences in overall utility scores between patients and controls. Patients who had not experienced certain surgical complications had less favorable scores than patients who did (utility score for ostomy = 0.2 for patients without ostomy vs. 0.7 for patients with ostomy, p = 0.02).

Conclusions: This study …

Liver Late Effects In Childhood Cancer Survivors Treated With Radiation Therapy: A Pentec Comprehensive Review, Matthew D Hall, Rebecca M Howell, Andrew Jackson, Constance A Owens, Soleil Hernandez, Sharon M Castellino, Cecile M Ronckers, Louis S Constine, Julie A Bradley

Faculty, Staff and Student Publications

Purpose: A pediatric normal tissue effects in the clinic (PENTEC) comprehensive review of patients with childhood cancer who received radiation therapy (RT) to the liver was performed to develop models that may inform RT dose constraints for the liver and improve risk forecasting of toxicities.

Methods and materials: A systematic literature search was performed to identify published data on hepatic toxicities in children. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. Complications from both whole and partial liver irradiation were considered. For whole liver irradiation, total body irradiation and non-total body irradiation …

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation In Unresectable Egfr-Mutant Nsclc: A Multicenter Retrospective Cohort Study, Amin H Nassar, So Yeon Kim, Jacqueline V Aredo, Jamie Feng, Frances Shepherd, Chao Xu, David Kaldas, Jhanelle E Gray, Thomas J Dilling, Joel W Neal, Heather A Wakelee, Yufei Liu, Steven H Lin, Tariq Abuali, Arya Amini, Yunan Nie, Tejas Patil, Anastasiya Lobachov, Jair Bar, Bailey Fitzgerald, Yu Fujiwara, Thomas U Marron, Rohit Thummalapalli, Helena Yu, Dwight H Owen, John Sharp, Saira Farid, Pedro Rocha, Edurne Arriola, Angelica D'Aiello, Haiying Cheng, Ryan Whitaker, Kaushal Parikh, Yash Ashara, Luxi Chen, Kamya Sankar, Jeremy P Harris, Misako Nagasaka, Adanma Ayanambakkam, Ana I Velazquez, Meera Ragavan, Jessica J Lin, Zofia Piotrowska, Molly Wilgucki, Joshua Reuss, Heike Luders, Christian Grohe, Javier Baena Espinar, Ella Feiner, Salman R Punekar, Shruti Gupta, Ticiana Leal, David J Kwiatkowski, Raymond H Mak, Elio Adib, Abdul Rafeh Naqash, Sarah B Goldberg

Faculty, Staff and Student Publications

Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.

Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology …

Network Meta-Analysis Of Car T-Cell Therapy For The Treatment Of 3l+ R/R Lbcl After Using Published Comparative Studies, Olalekan O Oluwole, Sattva S Neelapu, Markqayne D Ray, Eve H Limbrick-Oldfield, Sally W Wade, Steve Kanters, Anik R Patel, Frederick L Locke

Faculty, Staff and Student Publications

Introduction: Studies have compared chimeric antigen receptor (CAR) T-cell therapies and salvage chemotherapy in relapsed/refractory large B-cell lymphoma (LBCL) patients, but further evidence of their relative effectiveness is warranted.

Methods: Our systematic review identified studies comparing efficacy and safety outcomes of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel) and tisagenlecleucel (tisa-cel) trials to salvage chemotherapy cohorts in LBCL patients with ≥2 prior lines of treatment; and an extended evidence network included indirect comparisons comparing CAR T-cell therapies. We conducted network meta-analyzes using Bayesian hierarchical modeling.

Results: Three studies comparing ZUMA-1 (axi-cel), TRANSCEND (liso-cel) and JULIET (tisa-cel) trials to salvage chemotherapy within …

Deformable Motion Compensation In Interventional Cone-Beam Ct With A Context-Aware Learned Autofocus Metric, Heyuan Huang, Yixuan Liu, Jeffrey H Siewerdsen, Alexander Lu, Yicheng Hu, Wojciech Zbijewski, Mathias Unberath, Clifford R Weiss, Alejandro Sisniega

Faculty, Staff and Student Publications

Purpose: Interventional Cone-Beam CT (CBCT) offers 3D visualization of soft-tissue and vascular anatomy, enabling 3D guidance of abdominal interventions. However, its long acquisition time makes CBCT susceptible to patient motion. Image-based autofocus offers a suitable platform for compensation of deformable motion in CBCT, but it relies on handcrafted motion metrics based on first-order image properties and that lack awareness of the underlying anatomy. This work proposes a data-driven approach to motion quantification via a learned, context-aware, deformable metric, VIFDL , that quantifies the amount of motion degradation as well as the realism of the structural anatomical content in the image. …

Novel Cancer Prevention Strategies In Individuals With Hereditary Cancer Syndromes: Focus On Brca1, Brca2, And Lynch Syndrome, Charles M Bowen, Kaitlin Demarest, Eduardo Vilar, Payal D Shah

Faculty, Staff and Student Publications

Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1, BRCA2, or LS-associated …

A Comprehensive Investigation Of The Performance Of A Commercial Scintillator System For Applications In Electron Flash Radiotherapy, Kevin Liu, Shannon Holmes, Emil Schüler, Sam Beddar

Faculty, Staff and Student Publications

Background: Dosimetry in ultra-high dose rate (UHDR) beamlines is significantly challenged by limitations in real-time monitoring and accurate measurement of beam output, beam parameters, and delivered doses using conventional radiation detectors, which exhibit dependencies in ultra-high dose-rate (UHDR) and high dose-per-pulse (DPP) beamline conditions.

Purpose: In this study, we characterized the response of the Exradin W2 plastic scintillator (Standard Imaging, Inc.), a water-equivalent detector that provides measurements with a time resolution of 100 Hz, to determine its feasibility for use in UHDR electron beamlines.

Methods: The W2 scintillator was exposed to an UHDR electron beam with different beam parameters by …

Cascade Genetic Testing: An Underutilized Pathway To Equitable Cancer Care?, Roni Nitecki Wilke, Erica M Bednar, Sara Pirzadeh-Miller, Sayoni Lahiri, Isabel C Scarinci, Charles A Leath Iii, Melissa K Frey, Karen H Lu, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted …

Mortality In Recipients Of Allogeneic Haematopoietic Cell Transplantation In The Era Of Cytomegalovirus Primary Prophylaxis: A Single-Centre Retrospective Experience, Anthony Febres-Aldana, Fareed Khawaja, Oscar Morado-Aramburo, Terri Lynn Shigle, Gabriela Rondon, Joseph Sassine, Amy Spallone, Krithika Srinivasan, Jeremy Ramdial, Amin Alousi, Richard Champlin, George Chen, May Daher, Katayoun Rezvani, Ella J Ariza-Heredia, Elizabeth J Shpall, Roy F Chemaly

Faculty, Staff and Student Publications

Objectives: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes.

Methods: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, …

Association Of Tea And Coffee Consumption And Biliary Tract Cancer Risk: The Biliary Tract Cancers Pooling Project, Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T Chan, Veronika Fedirko, Gary E Fraser, Neal D Freedman, Graham G Giles, Patricia Hartge, Verena Katzke, Synnove F Knutsen, James Lacey, Linda M Liao, Juhua Luo, Roger L Milne, Katie M O'Brien, Ulrike Peters, Jenny N Poynter, Mark P Purdue, Kim Robien, Sven Sandin, Dale P Sandler, Veronica W Setiawan, Jae H Kang, Tracey G Simon, Rashmi Sinha, Trang Vopham, Stephanie J Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A Mcglynn, Peter T Campbell, Mei-Hsuan Lee, Jill Koshiol

Faculty, Staff and Student Publications

Background and aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach and results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and < 3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR< 3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers.

Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Utility Of Whole Slide Imaging For Intraoperative Consultation: Experience Of A Large Academic Center, Ahmed Shehabeldin, Prih Rohra, Linton D Sellen, Jianping Zhao, Doaa Alqaidy, Hermineh Aramin, Nadia Hameed, Ydamis Estrella Perez, Zongshan Lai, Yi Tat Tong, Denái R Milton, Mary E Edgerton, Gregory Fuller, Donna Hansel, Victor G Prieto, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Context.—: In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation.

Objective.—: To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation.

Design.—: Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 μm/pixel). The slides were deidentified, and a short relevant clinical history was provided for …

Development And Standardization Of An Osteoradionecrosis Classification System In Head And Neck Cancer: Implementation Of A Risk-Based Model, Erin E Watson, Katrina Hueniken, Junhyung Lee, Shao Hui Huang, Amr El Maghrabi, Wei Xu, Amy C Moreno, C Jillian Tsai, Ezra Hahn, Andrew J Mcpartlin, Christopher M K L Yao, David P Goldstein, John R De Almeida, John N Waldon, Clifton D Fuller, Andrew J Hope, Salvatore L Ruggiero, Michael Glogauer, Ali A Hosni

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

Methods: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity …

Dyadic Yoga For Head And Neck Cancer Patients Undergoing Chemoradiation And Their Family Caregivers, Kathrin Milbury, David I Rosenthal, Yisheng Li, An Thuy Ngo-Huang, Smitha Mallaiah, Sania Yousuf, Clifton D Fuller, Carol Lewis, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Objectives: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants.

Methods: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. …