Genetic Phenomena Commons^™

Postoperative Management Of Recurrence After Radiosurgery And Surgical Resection For Brain Metastases And Predicting Benefit From Adjuvant Radiation, Samantha M Buszek, Benjamin Tran, James P Long, Dershan Luo, Dima Suki, Jing Li, Sherise Ferguson, Caroline Chung

Faculty, Staff and Student Publications

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 …

Accelerating Artificial Intelligence: How Federated Learning Can Protect Privacy, Facilitate Collaboration, And Improve Outcomes, Malhar Patel, Ittai Dayan, Elliot K Fishman, Mona Flores, Fiona J Gilbert, Michal Guindy, Eugene J Koay, Michael Rosenthal, Holger R Roth, Marius G Linguraru

Faculty, Staff and Student Publications

Cross-institution collaborations are constrained by data-sharing challenges. These challenges hamper innovation, particularly in artificial intelligence, where models require diverse data to ensure strong performance. Federated learning (FL) solves data-sharing challenges. In typical collaborations, data is sent to a central repository where models are trained. With FL, models are sent to participating sites, trained locally, and model weights aggregated to create a master model with improved performance. At the 2021 Radiology Society of North America's (RSNA) conference, a panel was conducted titled "Accelerating AI: How Federated Learning Can Protect Privacy, Facilitate Collaboration and Improve Outcomes." Two groups shared insights: researchers from …

Editorial: Non-Coding Genome And Endocrinology: From Bench To Bedside, Radu Pirlog, Kinga Nemeth, George Adrian Calin

Faculty, Staff and Student Publications

No abstract provided.

Lysosomal Tmem9-Lamtor4-Controlled Mtor Signaling Integrity Is Required For Mammary Tumorigenesis, Shengzhe Zhang, Sung Ho Lee, Litong Nie, Yuanjian Huang, Gengyi Zou, Youn-Sang Jung, Sohee Jun, Jie Zhang, Esther M Lien, Junjie Chen, Jae-Il Park

Faculty, Staff and Student Publications

No abstract provided.

Late Effects Of Craniospinal Irradiation Using Electron Spinal Fields For Pediatric Patients With Cancer, Brian De, Marcus A Florez, Ethan B Ludmir, Moshe H Maor, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Eric L Chang, Anita Mahajan, Arnold C Paulino

Faculty, Staff and Student Publications

Purpose: For children, craniospinal irradiation (CSI) with photons is associated with significant toxic effects. The use of electrons for spinal fields is hypothesized to spare anterior structures but the long-term effects remain uncertain. We studied late effects of CSI using electrons for spinal radiation therapy (RT).

Methods and materials: Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution between 1983 and 2014 were reviewed. Median age at RT was 5 (range, 1-14) years. The most common histologies were medulloblastoma/primitive neuroectodermal tumor (59%) and ependymoma (8%). The median prescribed dose to the entire …

The Importance Of "When" In Calorie Restriction-Induced Lifespan Extension, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

No abstract provided.

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …

Less Is More? First Impressions From Cosmic-313, Pavlos Msaouel

Faculty, Staff and Student Publications

The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma. The first results presented at the 2022 European Society of Medical Oncology Congress are a milestone for the renal cell carcinoma field because they signal the advent of triplet combinations as potential treatment options for our patients. The present commentary highlights some considerations and potential next steps based on these first impressions.

Phase 1/2 Study Of Epacadostat In Combination With Durvalumab In Patients With Metastatic Solid Tumors, Aung Naing, Alain P Algazi, Gerald S Falchook, Benjamin C Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B Mettu, Pierre L Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R Patel

Faculty, Staff and Student Publications

Background: Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.

Methods: The open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.

Results: The most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) …

Radiation Therapy Can Be Safely Incorporated Into Pretransplantation Treatment Regimens For Patients With Multiple Myeloma, Ethan P Damron, Muzaffar H Qazilbash, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Gabriela Rondon, Chitra Hosing, Richard E Champlin, Qaiser Bashir, Elizabeth J Shpall, Mark K Knafl, Hans C Lee, Elisabet E Manasanch, Krina Patel, Sheeba K Thomas, Robert Z Orlowski, Donna M Weber, Chelsea C Pinnix, Jillian R Gunther

Faculty, Staff and Student Publications

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM …

Editorial: Interplay Between Epigenetic Modifiers And Transcription Factors In Driving Cancer Progression, Yongyong Yang, Annalisa Di Ruscio, Satoshi Inoue, Guocan Wang, Shuai Gao

Faculty, Staff and Student Publications

No abstract provided.

Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav

Faculty, Staff and Student Publications

The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

Faculty, Staff and Student Publications

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Clinical Outcomes: Endoscopic Resection Of Duodenal Ampullary Lesions, Stephanie M Woo, Mark J Real, Brett M Will, Eric J Kim, Jiling Chou, Ahmed A Alsaiari, Ahmad Nakshabandi, Walid M Chalhoub, Nadim G Haddad

Faculty, Staff and Student Publications

Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews. The objective of this study is to describe endoscopic papillectomy outcomes to further refine management guidelines.

Methods: This is a retrospective study of patients who underwent endoscopic papillectomy. Demographic data were included. Details regarding lesions and procedures were also collected, including endoscopic impression, size, resection method and adjunctive …

Easy Nanostring Ncounter Data Analysis With The Nanotube, Caleb A Class, Caiden J Lukan, Christopher A Bristow, Kim-Anh Do

Faculty, Staff and Student Publications

Summary: The NanoTube is an open-source pipeline that simplifies the processing, quality control, normalization and analysis of NanoString nCounter gene expression data. It is implemented in an extensible R library, which performs a variety of gene expression analysis techniques and contains additional functions for integration with other R libraries performing advanced NanoString analysis techniques. Additionally, the NanoTube web application is available as a simple tool for researchers without programming expertise.

Availability and implementation: The NanoTube R package is available on Bioconductor under the GPL-3 license (https://www.bioconductor.org/packages/NanoTube/). The R-Shiny application can be downloaded at https://github.com/calebclass/Shiny-NanoTube, or a simplified …

Survival Outcomes Used To Validate Version 9 Of The American Joint Committee On Cancer Staging System For Appendiceal Cancer, Lauren M Janczewski, Amanda E Browner, Joseph H Cotler, Heidi Nelson, Sanjay Kakar, Norman J Carr, Nader N Hanna, Andreana N Holowatyj, Richard M Goldberg, M Kay Washington, Elliot A Asare, Michael J Overman, American Joint Committee On Cancer Expert Panel On Cancers For The Lower Gastrointestinal Appendix Disease Site

Faculty, Staff and Student Publications

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 …

Treatment De-Escalation In Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia: The Emerging Role Of Chemotherapy-Free Regimens, Fadi G Haddad, Jacki Sawyers, Nicholas J Short

Faculty, Staff and Student Publications

The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many …

3,3′-Diindolylmethane Augments 5-Fluorouracil-Inducedgrowth Suppression In Gastric Cancer Cells Through Suppression Of The Akt/Gsk-3Β And Wnt/Beta-Catenin, Cong Shan Li, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Gastric cancer (GC) is one of the most lethal cancers in South Korea, and it is a cancer of concern worldwide. 5-fluorouracil (5-Fu) is commonly used as the first-line therapy for advanced GC; however, its side effects often limit the dosage range and impair patients' quality of life. Due to the limitations of current chemotherapy, new anticancer therapies are urgently needed. 3,3'-diindolylmethane (DIM) has been reported to have the ability to protect against various types of cancer. Our study aimed to elucidate the anticancer effect of DIM in GC when treated with the chemotherapeutic agent 5-Fu. In our results, combined …

Bayesian Single-To-Double Arm Transition Design Using Both Short-Term And Long-Term Endpoints, Tianlin Xu, Haolun Shi, Ruitao Lin

Faculty, Staff and Student Publications

The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials. Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. …

Evolutionary History Of Transformation From Chronic Lymphocytic Leukemia To Richter Syndrome, Erin M Parry, Ignaty Leshchiner, Romain Guièze, Connor Johnson, Eugen Tausch, Sameer A Parikh, Camilla Lemvigh, Julien Broséus, Sébastien Hergalant, Conor Messer, Filippo Utro, Chaya Levovitz, Kahn Rhrissorrakrai, Liang Li, Daniel Rosebrock, Shanye Yin, Stephanie Deng, Kara Slowik, Raquel Jacobs, Teddy Huang, Shuqiang Li, Geoff Fell, Robert Redd, Ziao Lin, Binyamin A Knisbacher, Dimitri Livitz, Christof Schneider, Neil Ruthen, Liudmila Elagina, Amaro Taylor-Weiner, Bria Persaud, Aina Martinez, Stacey M Fernandes, Noelia Purroy, Annabelle J Anandappa, Jialin Ma, Julian Hess, Laura Z Rassenti, Thomas J Kipps, Nitin Jain, William Wierda, Florence Cymbalista, Pierre Feugier, Neil E Kay, Kenneth J Livak, Brian P Danysh, Chip Stewart, Donna Neuberg, Matthew S Davids, Jennifer R Brown, Laxmi Parida, Stephan Stilgenbauer, Gad Getz, Catherine J Wu

Faculty, Staff and Student Publications

Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. …

Risk Stratification Of Postoperative Cardiopulmonary Toxicity After Trimodality Therapy For Esophageal Cancer, Roman O Kowalchuk, Grant M Spears, Lindsay K Morris, Dawn Owen, Harry H Yoon, Krishan Jethwa, Michael D Chuong, Matthew J Ferris, Michael G Haddock, Christopher L Hallemeier, Dennis Wigle, Steven H Lin, Kenneth W Merrell

Faculty, Staff and Student Publications

Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.

Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used.

Results: From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and …

A Th2-Score In The Tumor Microenvironment As A Predictive Biomarker Of Response To Bacillus Calmette Guérin In Patients With Non-Muscle Invasive Bladder Carcinoma: A Retrospective Study, Gustavo Martín Villoldo, María Teresa Pombo, Mariana Aris, Joaquín Chemi, Pablo Mandó, Supriya Nagaraju, Juan Camean, Adrián Burioni, Deborah Egea, Mora Amat, José León Mellado, José Mordoh, Alberto Villaronga, María Marcela Barrio

Faculty, Staff and Student Publications

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ …

Clinical Insights Into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, And Future Directions, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or …

Pre-Epithelialized Cryopreserved Tracheal Allograft For Neo-Trachea Flap Engineering, Ning Zeng, Youbai Chen, Yewen Wu, Mengqing Zang, Rene D Largo, Edward I Chang, Mark V Schaverien, Peirong Yu, Qixu Zhang

Faculty, Staff and Student Publications

Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection.

Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique …

Stem Cell Theory Of Cancer: Origin Of Metastasis And Sub-Clonality, Shi-Ming Tu, Cesar Moran, William Norton, Niki M Zacharias

Faculty, Staff and Student Publications

Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and …

Chd1, A Multifaceted Epigenetic Remodeler In Prostate Cancer, Haoyan Li, Loraine Gigi, Di Zhao

Faculty, Staff and Student Publications

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1's …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

Segmentation Stability Of Human Head And Neck Cancer Medical Images For Radiotherapy Applications Under De-Identification Conditions: Benchmarking Data Sharing And Artificial Intelligence Use-Cases, Jaakko Sahlsten, Kareem A Wahid, Enrico Glerean, Joel Jaskari, Mohamed A Naser, Renjie He, Benjamin H Kann, Antti Mäkitie, Clifton D Fuller, Kimmo Kaski

Faculty, Staff and Student Publications

BACKGROUND: Demand for head and neck cancer (HNC) radiotherapy data in algorithmic development has prompted increased image dataset sharing. Medical images must comply with data protection requirements so that re-use is enabled without disclosing patient identifiers. Defacing, i.e., the removal of facial features from images, is often considered a reasonable compromise between data protection and re-usability for neuroimaging data. While defacing tools have been developed by the neuroimaging community, their acceptability for radiotherapy applications have not been explored. Therefore, this study systematically investigated the impact of available defacing algorithms on HNC organs at risk (OARs).

METHODS: A publicly available dataset …

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …