Medical Specialties Commons^™

Young-Onset Rectal Cancer: Unique Tumoral Microbiome And Correlation With Response To Neoadjuvant Therapy, Michael G White, Ashish Damania, Jumanah Alshenaifi, Pranoti Sahasrabhojane, Oliver Peacock, Jillian Losh, Matthew C Wong, Zuzana Lutter-Berkova, George J Chang, Andrew Futreal, Jennifer A Wargo, Nadim J Ajami, Scott Kopetz, Y Nancy You

Faculty, Staff and Student Publications

OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

METHODS: YORC (old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to …

Peripheral Levels Of The Brain-Derived Neurotrophic Factor In Coronary Artery Disease: A Systematic Review And Meta-Analysis, Parnian Shobeiri, Amir Hossein Behnoush, Amirmohammad Khalaji, Antonio Lucio Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls.

METHODS: We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted …

Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity, Thomas B K Watkins, Emma C Colliver, Matthew R Huska, Tom L Kaufmann, Emilia L Lim, Cody B Duncan, Kerstin Haase, Peter Van Loo, Charles Swanton, Nicholas Mcgranahan, Roland F Schwarz

Faculty, Staff and Student Publications

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient's disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase's ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.

Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker

Faculty, Staff and Student Publications

People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments about constrained individuals who do not persist. Using a developmental social inference task (Study 1a: n = 124 U.S. children, 5 to 12 years of age; Study 1b [n = 135] and Study 2 [n = 120]: U.S. adults), the present research tested whether persistence stories lead people to infer that a constrained individual who does not persist, and instead accepts the lower-quality option that is available to them, prefers it over a …

Prevalence Of Pituitary Hormone Dysfunction Following Radiotherapy For Sinonasal And Nasopharyngeal Malignancies, Kevin J Contrera, Jack Phan, Steven G Waguespack, Mohammed Aldehaim, Xin Wang, Tze Yee Lim, Dianna B Roberts, C David Fuller, Michael T Spiotto, Shaan M Raza, Franco Demonte, Ehab Y Hanna, Shirley Y Su

Faculty, Staff and Student Publications

BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation.

METHODS: Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated.

RESULTS: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P …

Single-Agent Lenalidomide Maintenance After Upfront Autologous Stem Cell Transplant For Newly Diagnosed Multiple Myeloma: The Md Anderson Experience, Oren Pasvolsky, Denái R Milton, Adeel Masood, Sophiya S Sami, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Arsalan Saeed, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single-center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single-agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4-82.3) years, and high-risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03-139.6) months. After a median follow-up of 47.9 (range 2.9-171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2-61.4) months and 111.3 …

A Machine Learning Approach That Measures Ph Using Acidocest Mri Of Iopamidol, Tianzhe Li, Julio Cárdenas-Rodríguez, Priya N Trakru, Mark D Pagel

Faculty, Staff and Student Publications

Tumor acidosis is an important biomarker for aggressive tumors, and extracellular pH (pHe) of the tumor microenvironment can be used to predict and evaluate tumor responses to chemotherapy and immunotherapy. AcidoCEST MRI measures tumor pHe by exploiting the pH-dependent chemical exchange saturation transfer (CEST) effect of iopamidol, an exogenous CT agent repurposed for CEST MRI. However, all pH fitting methodologies for acidoCEST MRI data have limitations. Herein we present results of the application of machine learning for extracting pH values from CEST Z-spectra of iopamidol. We acquired 36,000 experimental CEST spectra from 200 phantoms of iopamidol prepared at five concentrations, …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar

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Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Controversy And Consensus On The Management Of Elevated Sperm Dna Fragmentation In Male Infertility: A Global Survey, Current Guidelines, And Expert Recommendations, Ala'a Farkouh, Ashok Agarwal, Taha Abo-Almagd Abdel-Meguid Hamoda, Parviz Kavoussi, Ramadan Saleh, Armand Zini, Mohamed Arafa, Ahmed M Harraz, Murat Gul, Vilvapathy Senguttuvan Karthikeyan, Damayanthi Durairajanayagam, Amarnath Rambhatla, Florence Boitrelle, Eric Chung, Ponco Birowo, Tuncay Toprak, Ramy Abou Ghayda, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Fotios Dimitriadis, Giorgio I Russo, Ioannis Sokolakis, Taymour Mostafa, Konstantinos Makarounis, Imad Ziouziou, Shinnosuke Kuroda, Marion Bendayan, Raneen Sawaid Kaiyal, Andrian Japari, Mara Simopoulou, Lucia Rocco, Nicolas Garrido, Nazim Gherabi, Kadir Bocu, Oguzhan Kahraman, Tan V Le, Christine Wyns, Kelton Tremellen, Selcuk Sarikaya, Sheena Lewis, Donald P Evenson, Edmund Ko, Aldo E Calogero, Fahmi Bahar, Marlon Martinez, Andrea Crafa, Quang Nguyen, Rafael F Ambar, Giovanni Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alarbid, Akira Tsujimura, Alireza Kheradmand, Christina Anagnostopoulou, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Germar-Michael Pinggera, Priyank Kothari, Nasser Mogharabian, Sava Micic, Sheryl Homa, Sara Darbandi, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Marjan Sabbaghian, Wael Ibrahim, Ryan P Smith, Christopher Chee Kong Ho, Jean De La Rosette, Ahmed I El-Sakka, Mirko Preto, Cătălina Zenoaga-Barbăroșie, Saad Mohammed Abumelha, Aykut Baser, Kaan Aydos, Liliana Ramirez-Dominguez, Vijay Kumar, Teng Aik Ong, Tiago Cesar Mierzwa, Ricky Adriansjah, Saleem A Banihani, Kasonde Bowa, Shinichiro Fukuhara, Marcelo Rodriguez Peña, Mohamad Moussa, Umut Çağın Ari, Chak-Lam Cho, Nicholas N Tadros, Muhammet Rasit Ugur, Edouard Amar, Marco Falcone, Frederic Romain Santer, Arif Kalkanli, Keshab Kumar Karna, Kareim Khalafalla, Ranjit B Vishwakarma, Federica Finocchi, Carlo Giulioni, Erman Ceyhan, Gökhan Çeker, Chadi Yazbeck, Osvaldo Rajmil, Mehmet Yilmaz, Baris Altay, Trenton L Barrett, Kay Seong Ngoo, Shubhadeep Roychoudhury, Gianmaria Salvio, Haocheng Lin, Ates Kadioglu, Massimiliano Timpano, Tomer Avidor-Reiss, Lukman Hakim, Puneet Sindhwani, Giorgio Franco, Rajender Singh, Filippo Giacone, Mikhail Ruzaev, Raghavender Kosgi, Nikolaos Sofikitis, Ayad Palani, Gokhan Calik, Deniz Kulaksız, Davor Jezek, Manaf Al Hashmi, Panagiotis Drakopoulos, Huda Omran, Sofia Leonardi, Ciler Celik-Ozenci, Nur Dokuzeylül Güngör, Jonathan Ramsay, Toshiyasu Amano, Emrullah Sogutdelen, Gede Wirya Kusuma Duarsa, Koji Chiba, Sunil Jindal, Missy Savira, Luca Boeri, Edson Borges, Deepak Gupte, Fatih Gokalp, Guadalupe Hernández Hebrard, Suks Minhas, Rupin Shah, Global Andrology Forum

Faculty, Staff and Student Publications

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.

Materials and methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate …

Regression Analysis Of General Mixed Recurrent Event Data, Ryan Sun, Dayu Sun, Liang Zhu, Jianguo Sun

Faculty, Staff and Student Publications

In modern biomedical datasets, it is common for recurrent outcomes data to be collected in an incomplete manner. More specifically, information on recurrent events is routinely recorded as a mixture of recurrent event data, panel count data, and panel binary data; we refer to this structure as general mixed recurrent event data. Although the aforementioned data types are individually well-studied, there does not appear to exist an established approach for regression analysis of the three component combination. Often, ad-hoc measures such as imputation or discarding of data are used to homogenize records prior to the analysis, but such measures lead …

Correction: Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello

Faculty, Staff and Student Publications

No abstract provided.

Gut Microbiome In Patients With Early-Stage And Late-Stage Melanoma, Russell G Witt, Samuel H Cass, Tiffaney Tran, Ashish Damania, Emelie E Nelson, Elizabeth Sirmans, Elizabeth M Burton, Manoj Chelvanambi, Sarah Johnson, Hussein A Tawbi, Jeffrey E Gershenwald, Michael A Davies, Christine Spencer, Aditya Mishra, Matthew C Wong, Nadim J Ajami, Christine B Peterson, Carrie R Daniel, Jennifer A Wargo, Jennifer L Mcquade, Kelly C Nelson

Faculty, Staff and Student Publications

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.

OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.

DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at …

Automated Cellular-Level Dual Global Fusion Of Whole-Slide Imaging For Lung Adenocarcinoma Prognosis, Songhui Diao, Pingjun Chen, Eman Showkatian, Rukhmini Bandyopadhyay, Frank R Rojas, Bo Zhu, Lingzhi Hong, Muhammad Aminu, Maliazurina B Saad, Morteza Salehjahromi, Amgad Muneer, Sheeba J Sujit, Carmen Behrens, Don L Gibbons, John V Heymach, Neda Kalhor, Ignacio I Wistuba, Luisa M Solis Soto, Jianjun Zhang, Wenjian Qin, Jia Wu

Faculty, Staff and Student Publications

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce …

Kunitz-Type Protease Inhibitor Tfpi2 Remodels Stemness And Immunosuppressive Tumor Microenvironment In Glioblastoma, Lizhi Pang, Madeline Dunterman, Songlin Guo, Fatima Khan, Yang Liu, Erfan Taefi, Atousa Bahrami, Changiz Geula, Wen-Hao Hsu, Craig Horbinski, Charles David James, Peiwen Chen

Faculty, Staff and Student Publications

Glioblastoma (GBM) tumors consist of multiple cell populations, including self-renewing glioblastoma stem cells (GSCs) and immunosuppressive microglia. Here we identified Kunitz-type protease inhibitor TFPI2 as a critical factor connecting these cell populations and their associated GBM hallmarks of stemness and immunosuppression. TFPI2 promotes GSC self-renewal and tumor growth via activation of the c-Jun N-terminal kinase-signal transducer and activator of transcription (STAT)3 pathway. Secreted TFPI2 interacts with its functional receptor CD51 on microglia to trigger the infiltration and immunosuppressive polarization of microglia through activation of STAT6 signaling. Inhibition of the TFPI2-CD51-STAT6 signaling axis activates T cells and synergizes with anti-PD1 therapy …

Selection And Prejudice: Addressing Clinical Trial Disparities With A Review Of Current Shortcomings And Future Directions, Kelsey L Corrigan, Michael K Rooney, Ramez Kouzy, Gohar Manzar, Charles R Thomas, Ethan B Ludmir

Faculty, Staff and Student Publications

Growing evidence has demonstrated significant, persistent, and widespread disparities in cancer clinical trial enrollment across myriad disease sites and target populations. Although mechanisms underlying such disparities are complex and multifactorial, clinical trial eligibility criteria may serve as a key structural barrier to equitable and diverse trial enrollment. In this review, we provide an overview of the data describing historical and current disparities in cancer clinical trial enrollment and subsequently describe several patient-, institution-, and trial-related factors which appear to be key drivers of enrollment inequity, with specific discussion regarding the impact of eligibility criteria. We further describe the landscape of …

The Concise Guide To Pharmacology 2023/24: Enzymes, Stephen P H Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Jamie A Davies, Stephanie Annett, Detlev Boison, Kathryn Elisa Burns, Carmen Dessauer, Jurg Gertsch, Nuala Ann Helsby, Angelo A Izzo, Rennolds Ostrom, Andreas Papapetropoulos, Nigel J Pyne, Susan Pyne, Tracy Robson, Roland Seifert, Johannes-Peter Stasch, Csaba Szabo, Mario Van Der Stelt, Albert Van Der Vliet, Val Watts, Szu Shen Wong

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The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It …

Clinical And Biological Significance Of Circulating Mirnas In Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation, Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin

Faculty, Staff and Student Publications

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.

Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.

Results: …

Correspondence On "Points To Consider In The Practice Of Postmortem Genetic Testing: A Statement Of The American College Of Medical Genetics And Genomics (Acmg)" By Deignan, Et Al, Fowzan S Alkuraya, Kathryn J Gray, Siddharth K Prakash, Monica H Wojcik, Angela E Lin

Faculty, Staff and Student Publications

No abstract provided.

Joint Vestibular Schwannoma Enlargement Prediction And Segmentation Using A Deep Multi-Task Model, Kai Wang, Nicholas A George-Jones, Liyuan Chen, Jacob B Hunter, Jing Wang

Faculty, Staff and Student Publications

Objective: To develop a deep-learning-based multi-task (DMT) model for joint tumor enlargement prediction (TEP) and automatic tumor segmentation (TS) for vestibular schwannoma (VS) patients using their initial diagnostic contrast-enhanced T1-weighted (ceT1) magnetic resonance images (MRIs).

Methods: Initial ceT1 MRIs for VS patients meeting the inclusion/exclusion criteria of this study were retrospectively collected. VSs on the initial MRIs and their first follow-up scans were manually contoured. Tumor volume and enlargement ratio were measured based on expert contours. A DMT model was constructed for jointly TS and TEP. The manually segmented VS volume on the initial scan and the tumor enlargement label …

Suspected Bronchiectasis And Mortality In Adults With A History Of Smoking Who Have Normal And Impaired Lung Function : A Cohort Study, Alejandro A Diaz, Wei Wang, Jose L Orejas, Rim Elalami, Wojciech R Dolliver, Pietro Nardelli, Ruben San José Estépar, Bina Choi, Carrie L Pistenmaa, James C Ross, Diego J Maselli, Andrew Yen, Kendra A Young, Gregory L Kinney, Michael H Cho, Raul San José Estépar

Faculty, Staff and Student Publications

Background: Bronchiectasis in adults with chronic obstructive pulmonary disease (COPD) is associated with greater mortality. However, whether suspected bronchiectasis-defined as incidental bronchiectasis on computed tomography (CT) images plus clinical manifestation-is associated with increased mortality in adults with a history of smoking with normal spirometry and preserved ratio impaired spirometry (PRISm) is unknown.

Objective: To determine the association between suspected bronchiectasis and mortality in adults with normal spirometry, PRISm, and obstructive spirometry.

Design: Prospective, observational cohort.

Setting: The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study.

Participants: 7662 non-Hispanic Black or White adults, aged 45 to 80 years, with 10 …

Advances In Vaccine Development For Cancer Prevention And Treatment In Lynch Syndrome, Ana M Bolivar, Fahriye Duzagac, Krishna M Sinha, Eduardo Vilar

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Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal …

Emerging Therapeutics And Evolving Assessment Criteria For Intracranial Metastases In Patients With Oncogene-Driven Non-Small-Cell Lung Cancer, Kelsey Pan, Kyle Concannon, Jing Li, Jianjun Zhang, John V Heymach, Xiuning Le

Faculty, Staff and Student Publications

The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood-brain barrier. However, …

Cancer Germline Predisposing Variants And Late Mortality From Subsequent Malignant Neoplasms Among Long-Term Childhood Cancer Survivors: A Report From The St Jude Lifetime Cohort And The Childhood Cancer Survivor Study, Cheng Chen, Na Qin, Mingjuan Wang, Qian Dong, Saima Sultana Tithi, Yawei Hui, Wenan Chen, Gang Wu, Dennis Kennetz, Michael N Edmonson, Michael C Rusch, Andrew Thrasher, John Easton, Heather L Mulder, Nan Song, Noel-Marie Plonski, Kyla Shelton, Cindy Im, Matthew J Ehrhardt, Kim E Nichols, Wendy M Leisenring, Kayla L Stratton, Rebecca Howell, Yutaka Yasui, Smita Bhatia, Gregory T Armstrong, Kirsten K Ness, Melissa M Hudson, Jinghui Zhang, Hui Wang, Deo Kumar Srivastava, Leslie L Robison, Zhaoming Wang

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Background: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis).

Methods: In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or …

Trends In Radiation Dose To The Contralateral Breast During Breast Cancer Radiation Therapy, Gordon P Watt, Susan A Smith, Rebecca M Howell, Angélica Pérez-Andújar, Ann S Reiner, Laura Cerviño, Beryl Mccormick, Daniela Hess, Julia A Knight, Kathleen E Malone, Esther M John, Leslie Bernstein, Charles F Lynch, Lene Mellemkjær, Roy E Shore, Xiaolin Liang, Meghan Woods, John D Boice, Lawrence T Dauer, Jonine L Bernstein

Faculty, Staff and Student Publications

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in …

Risk Factors For Overweight And Obesity After Childhood Acute Lymphoblastic Leukemia In North America And Switzerland: A Comparison Of Two Cohort Studies, Fabiën N Belle, Christina Schindera, Marc Ansari, Gregory T Armstrong, Maja Beck-Popovic, Rebecca Howell, Wendy M Leisenring, Lillian R Meacham, Jochen Rössler, Ben D Spycher, Emily Tonorezos, Nicolas X Von Der Weid, Yutaka Yasui, Kevin C Oeffinger, Claudia E Kuehni

Faculty, Staff and Student Publications

Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors.

Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in …

Kras G12c In Advanced Nsclc: Prevalence, Co-Mutations, And Testing, Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M Kerr, Myung-Ju Ahn, Joshua R Kapp, Fernando A Soares, Yasushi Yatabe

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KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence …

International Association For The Study Of Lung Cancer Study Of Reproducibility In Assessment Of Pathologic Response In Resected Lung Cancers After Neoadjuvant Therapy, Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A Schalper, Ming-Sound Tsao, David P Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A Bunn, Mark G Kris, Chandra P Belani, Karen Kelly, Ignacio Wistuba

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Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable …

Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir

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The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.

Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan

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Medical device technology develops rapidly, and the life cycle of a medical device is much shorter than drugs. It is necessary to evaluate the safety and effectiveness of a medical device in a timely manner to keep up with technology flux. Bayesian methods provides an efficient approach to addressing this challenge. In this article, we review the characteristics of the Bayesian approach and some Bayesian designs that were commonly used in medical device regulatory setting, including Bayesian adaptive design, Bayesian diagnostic design, Bayesian multiregional design, and Bayesian label expansion study. We illustrate these designs with medical devices approved by the …