Biomedical Informatics Commons^™

Dna Damage Response-Related Proteins Are Prognostic For Outcome In Both Adult And Pediatric Acute Myelogenous Leukemia Patients: Samples From Adults And From Children Enrolled In A Children's Oncology Group Study, Stefan E Hubner, Eduardo S De Camargo Magalhães, Fieke W Hoff, Brandon D Brown, Yihua Qiu, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In …

Comparison Of Four Clinical Prognostic Scores In Patients With Advanced Gastric And Esophageal Cancer, Lucy X Ma, Osvaldo Espin-Garcia, Yvonne Bach, Hiroko Aoyama, Michael J Allen, Xin Wang, Gail E Darling, Jonathan Yeung, Carol J Swallow, Savtaj Brar, Patrick Veit-Haibach, Sangeetha Kalimuthu, Rebecca Wong, Eric X Chen, Grainne M O'Kane, Raymond W Jang, Elena Elimova

Faculty, Staff and Student Publications

Background: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer.

Methods: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards …

Human Papillomavirus Status And Prognosis Of Oropharyngeal High-Grade Neuroendocrine Carcinoma, Luana G De Sousa, Felippe Lazar Neto, Eduardo A Dal Lago, Andrew Sikora, Ehab Hanna, Amy Moreno, Jack Phan, Bonnie S Glisson, Diana Bell, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established.

Methods: Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models.

Results: Thirty patients were included; most had a heavy (≥10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was …

Leukemic Phase Follicular Lymphoma In A Young Adult, Daniel Rivera, Wei Wang, Zubaidah Al-Jumaili, Zhihong Hu

Faculty, Staff and Student Publications

Background: Leukemic presentation of follicular lymphoma (FL) is uncommon, with most cases reported in older adults.

Design: This report describes an unusual case of a young adult diagnosed with leukemic phase of FL. We reviewed the existing literature on this rare presentation of the disease and its potential impact on patient outcomes.

Results: Leukemic phase of FL in young adults can be mistaken for other high-grade hematologic malignancies. Morphology assessment and ancillary testing, such as flow cytometry and FISH analysis, can assist in achieving an accurate diagnosis of the leukemic phase of FL. Notably, our young patient responded well to …

Impact Of High Neutrophil-To-Lymphocyte Ratio On Survival In Hospitalized Cancer Patients With Covid-19, Fernando A Díaz-Couselo, Santiago Flagel, Carla Nicolini, Sebastián Halac, Natalia Manzano, Marina Aguirre, Juan Rébora, Sandra Valle, Laura Noro, Chirayu Mohindroo, Florencia Mcallister, Marcelo Zylberman

Faculty, Staff and Student Publications

Neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic factor for mortality in COVID-19 patients. Our study aimed to evaluate the association between NLR at COVID-19 diagnosis and survival during the following 90 days in hospitalized patients with solid cancer. Between May 2020 and June 2021, 120 patients were included in a retrospective cohort study. Univariable analysis showed patients with an NLR > 8.3 were associated with an increased risk of death (HR: 4.34; 95% CI: 1.74-10.84) compared to patients with NLR < 3.82 and with NLR ≥3.82 and ≤8.30 (HR: 2.89; 95% CI: 1.32-6.36). Furthermore, on multivariable analysis, NLR > 8.30 independently correlated with increased mortality. In patients with solid malignancies with COVID-19, an NLR > 8.3 is associated with …

Deep Learning-Based Pathology Image Analysis Predicts Cancer Progression Risk In Patients With Oral Leukoplakia, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Roberta Rayra Martins-Chaves, Ricardo Santiago Gomez, Nadarajah Vigneswaran, Arunangshu Sarkar, William N William, Vassiliki Papadimitrakopoulou, Michelle Williams, Diana Bell, Doreen Palsgrove, Justin Bishop, John V Heymach, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Scott M Lippman, Curtis Rg Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models.

METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could …

Immune Checkpoint Gene Vsir Predicts Patient Prognosis In Acute Myeloid Leukemia And Myelodysplastic Syndromes, Kevin Yao, Emily Zhou, Evelien Schaafsma, Baoyi Zhang, Chao Cheng

Faculty, Staff and Students Publications

Background: Immune checkpoint proteins play critical functions during the immune response to cancer and have been targeted by immune checkpoint blockade therapy. V-domain Ig suppressor of T cell activation (VSIR) is one of these immune checkpoint genes and has been investigated extensively in recent years due to its conflicting roles in cancer immunity. Specifically, in acute myeloid leukemia (AML), the prognostic value of VSIR is debated.

Results: In both patient tumor samples and cancer cell lines we find that VSIR has the highest expression in AML out of all cancer types and, in AML, has the highest expression out of …

Prognostic Significance Of Acellular Mucin In Patients Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy (Crs/Hipec) For Appendiceal Neoplasms, Derek J Erstad, Kristen A Robinson, Karen Beaty, Safia Rafeeq, Yi-Ju Chiang, Kanwal Raghav, John P Shen, Michael J Overman, Wai Chin Foo, Melissa W Taggart, Paul F Mansfield, Richard E Royal, Keith F Fournier, Christopher P Scally

Faculty, Staff and Student Publications

Introduction: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients.

Methods: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed.

Results: Median age was 51 years, 70% were female, …

Emerging Treatments For Myelodysplastic Syndromes: Biological Rationales And Clinical Translation, Juan Jose Rodriguez-Sevilla, Vera Adema, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, nearly 50% of patients have no response to the treatment. Patients with MDS in whom HMA therapy has failed have a dismal prognosis and no approved second-line therapy options, so enrollment in clinical trials of experimental agents represents these patients' only chance for improved outcomes. A better understanding of the molecular and biological mechanisms underpinning MDS …

Spatially Resolved Single-Cell Assessment Of Pancreatic Cancer Expression Subtypes Reveals Co-Expressor Phenotypes And Extensive Intratumoral Heterogeneity, Hannah L Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S Winter, Kevin S Kapner, Scott P Ginebaugh, Sara A Väyrynen, Juha P Väyrynen, Chen Yuan, Andrew W Navia, Junning Wang, Annan Yang, Timothy L Bosse, Radha L Kalekar, Kristen E Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A Rubinson, Harshabad Singh, Kimberly Perez, James M Cleary, Thomas E Clancy, Jiping Wang, Joseph D Mancias, Lauren K Brais, Emma R Hill, Margaret M Kozak, David C Linehan, Richard F Dunne, Daniel T Chang, Albert C Koong, Aram F Hezel, William C Hahn, Alex K Shalek, Andrew J Aguirre, Jonathan A Nowak, Brian M Wolpin

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed …

Kynureninase Upregulation Is A Prominent Feature Of Nfr2-Activated Cancers And Is Associated With Tumor Immunosuppression And Poor Prognosis, Ricardo A León-Letelier, Ali H Abdel Sater, Yihui Chen, Soyoung Park, Ranran Wu, Ehsan Irajizad, Jennifer B Dennison, Hiroyuki Katayama, Jody V Vykoukal, Samir Hanash, Edwin J Ostrin, Johannes F Fahrmann

Faculty, Staff and Student Publications

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding gene NFE2L2 or a loss of function of its suppressor, Kelch-like ECH-associated protein 1 (KEAP1). NRF2 activation exerts pro-tumoral effects in part by altering cancer cell metabolism. Previously, we reported a novel mechanism of NRF2 tumoral immune suppression through the selective upregulation of the tryptophan-metabolizing enzyme kynureninase (KYNU) in lung adenocarcinoma. In the current study, we explored the relevance of NRF2-mediated KYNU upregulation across multiple cancer types. Specifically, …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Tung-Shing M Lih, Saravana M Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J Clark, Iga Kołodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A Wyczalkowski, Michael C Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe Da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A Reimers, Russell Pachynski, Alexander J Lazar, Arul M Chinnaiyan, Brian A Van Tine, Bing Zhang, Karin D Rodland, Gad Getz, D R Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W Marston Linehan, David Fenyö, Scott D Jewell, Gilbert S Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W Chan, Christopher J Ricketts, Alexey I Nesvizhskii, Hui Zhang, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

Multicenter International Study Of The Consensus Immunoscore For The Prediction Of Relapse And Survival In Early-Stage Colon Cancer, Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van Den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, Seongjun Han, Heather L Macgregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van De Water, Shannon Van Lent-Van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Bernard A Fox, Franck Pagès, Jérôme Galon

Faculty, Staff and Student Publications

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival …

Predicting The Risk Of A Clinical Event Using Longitudinal Data: The Generalized Landmark Analysis, Yi Yao, Liang Li, Brad Astor, Wei Yang, Tom Greene

Faculty, Staff and Student Publications

Background: In the development of prediction models for a clinical event, it is common to use the static prediction modeling (SPM), a regression model that relates baseline predictors to the time to event. In many situations, the data used in training and validation are from longitudinal studies, where predictor variables are time-varying and measured at clinical visits. But these data are not used in SPM. The landmark analysis (LA), previously proposed for dynamic prediction with longitudinal data, has interpretational difficulty when the baseline is not a risk-changing clinical milestone, as is often the case in observational studies of chronic disease …

Integrated Clinical Genotype-Phenotype Characteristics Of Early T-Cell Precursor Acute Lymphoblastic Leukemia, Matthew T Ye, Yi Wang, Zhuang Zuo, Steliana Calin, Hua He, Zhenya Tang, Elias J Jabbour, Gautam Borthakur, Yizhuo Zhang, Yaling Yang, M James You

Faculty, Staff and Student Publications

Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a unique immunophenotype and high treatment failure rate. The molecular genetic abnormalities and their prognostic impact in ETP-ALL patients are poorly understood.

Methods: The authors performed systematic analyses of the clinicopathologic features with an emphasis on molecular genetic aspects of 32 patients with ETP-ALL.

Results: The median age was 43 years (range, 16-71). The blasts were positive for cytoplasmic CD3 and CD7 and negative for CD1a and CD8. Other markers expressed included CD34 (88%), CD33 (72%), CD117 (68%), CD13 (58%), CD5 (partial, 56%), CD2 (38%), …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

Molecular Predictors Of Immunophenotypic Measurable Residual Disease Clearance In Acute Myeloid Leukemia, Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A Patel, Sheng F Cai, Linde A Miles, Robert L Bowman, Mark B Geyer, Andrew Dunbar, Zachary D Epstein-Peterson, Erin Mcgovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Eytan M Stein, Bartlomiej Getta, Maria E Arcila, Qi Gao, Juliet Barker, Brian C Shaffer, Esperanza B Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L Levine, Sergio A Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S Tallman, Mikhail Roshal, Aaron D Goldberg

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and …

Head And Neck Cancer Predictive Risk Estimator To Determine Control And Therapeutic Outcomes Of Radiotherapy (Hnc-Predictor): Development, International Multi-Institutional Validation, And Web Implementation Of Clinic-Ready Model-Based Risk Stratification For Head And Neck Cancer, Lisanne V Van Dijk, Abdallah Sr Mohamed, Sara Ahmed, Nafiul Nipu, G Elisabeta Marai, Kareem Wahid, Nanna M Sijtsema, Brandon Gunn, Adam S Garden, Amy Moreno, Andrew J Hope, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Background: Personalised radiotherapy can improve treatment outcomes of patients with head and neck cancer (HNC), where currently a 'one-dose-fits-all' approach is the standard. The aim was to establish individualised outcome prediction based on multi-institutional international 'big-data' to facilitate risk-based stratification of patients with HNC.

Methods: The data of 4611 HNC radiotherapy patients from three academic cancer centres were split into four cohorts: a training (n = 2241), independent test (n = 786), and external validation cohorts 1 (n = 1087) and 2 (n = 497). Tumour- and patient-related clinical variables were considered in a machine learning pipeline to predict overall …

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

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 …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Absolute Lymphocyte Count Recovery Following Initial Acute Myelogenous Leukemia Therapy: Implications For Adoptive Cell Therapy, John C Molina, Yimei Li, William R Otto, Tamara P Miller, Kelly D Getz, Carly Mccoubrey, Mark Ramos, Edward Krause, Lusha Cao, M Monica Gramatges, Karen Rabin, Michael Scheurer, Caitlin W Elgarten, Regina M Myers, Alix E Seif, Brian T Fisher, Nirali N Shah, Richard Aplenc

Faculty, Staff and Students Publications

Background: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML.

Procedure: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 …

Habitat Imaging Biomarkers For Diagnosis And Prognosis In Cancer Patients Infected With Covid-19, Muhammad Aminu, Divya Yadav, Lingzhi Hong, Elliana Young, Paul Edelkamp, Maliazurina Saad, Morteza Salehjahromi, Pingjun Chen, Sheeba J Sujit, Melissa M Chen, Bradley Sabloff, Gregory Gladish, Patricia M De Groot, Myrna C B Godoy, Tina Cascone, Natalie I Vokes, Jianjun Zhang, Kristy K Brock, Naval Daver, Scott E Woodman, Hussein A Tawbi, Ajay Sheshadri, J Jack Lee, David Jaffray, D Code Team, Carol C Wu, Caroline Chung, Jia Wu

Faculty, Staff and Student Publications

OBJECTIVES: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population.

METHODS: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and …

Prognostic Model For Predicting Overall And Cancer-Specific Survival Among Patients With Superficial Spreading Melanoma: A Seer Based Study, Qiang Ji, Jun Tang, Shulian Li, Junjie Chen

Faculty, Staff and Student Publications

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology …

Spatial Heterogeneity Of Infiltrating T Cells In High-Grade Serous Ovarian Cancer Revealed By Multi-Omics Analysis, Bin Yang, Xiong Li, Wei Zhang, Junpeng Fan, Yong Zhou, Wenting Li, Jingjing Yin, Xiaohang Yang, Ensong Guo, Xi Li, Yu Fu, Si Liu, Dianxing Hu, Xu Qin, Yingyu Dou, Rourou Xiao, Funian Lu, Zizhuo Wang, Tianyu Qin, Wei Wang, Qinghua Zhang, Shuaicheng Li, Ding Ma, Gordon B Mills, Gang Chen, Chaoyang Sun

Faculty, Staff and Student Publications

Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

Implications Of Ras Mutational Status In Subsets Of Patients With Newly Diagnosed Acute Myeloid Leukemia Across Therapy Subtypes, Daniel Rivera, Kunhwa Kim, Rashmi Kanagal-Shamanna, Gautam Borthakur, Guillermo Montalban-Bravo, Naval Daver, Courtney Dinardo, Nicholas J Short, Musa Yilmaz, Naveen Pemmaraju, Koichi Takahashi, Elias J Jabbour, Sherry Pierce, Marina Konopleva, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Activating mutations in RAS have been reported in about 10-15% of patients with AML; previous studies have not identified a prognostic significance. However, RAS mutations have emerged as a potential resistance mechanism to treatment with inhibitors of FLT3, IDH, and BCL2. We aimed to determine the characteristics and outcomes of patients with RAS-mutated (RAS-mut) AML across therapy subsets of 1410 patients newly diagnosed (ND AML). RAS-mut was observed in 273 (20%) patients. Overall, patients with RAS-mut AML had an estimated 3-year survival rate of 38% vs. 28% in those with RAS wild type (RAS-wt), p = .01. Among patients with …

Association Of Hematologic Response And Assay Sensitivity On The Prognostic Impact Of Measurable Residual Disease In Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Nicholas J Short, Chenqi Fu, Donald A Berry, Roland B Walter, Sylvie D Freeman, Christopher S Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Shouhao Zhou, Farhad Ravandi

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across clinical contexts, including its association with hematologic response and MRD assay sensitivity. We performed systematic literature review and meta-analysis of 48 studies that reported the association between MRD and overall survival (OS) or disease-free survival (DFS) in AML and provided information on the MRD threshold used and the hematologic response of the study population. Among studies limited to patients in complete remission (CR), the estimated 5-year OS for the MRD-negative and MRD-positive groups was …

Prognostic Impact Of Breslow Thickness In Acral Melanoma: A Retrospective Analysis, Xiaoting Wei, Yu Chen, Hong Yao, Di Wu, Hang Li, Rui Zhang, Zhihong Chi, Chuanliang Cui, Xue Bai, Lili Mao, Zhonghui Qi, Ke Li, Shijie Lan, Lizhu Chen, Rui Guo, Xinyu Yao, Bin Lian, Yan Kong, Jie Dai, Bixia Tang, Xuan Wang, Jeffrey E Gershenwald, Charles M Balch, Jun Guo, Lu Si

Faculty, Staff and Student Publications

Background: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited.

Objective: The objective of the study was to determine the prognostic impact of Breslow thickness in AM.

Methods: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression.

Results: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The …

The Single-Cell Immunogenomic Landscape Of B And Plasma Cells In Early-Stage Lung Adenocarcinoma, Dapeng Hao, Guangchun Han, Ansam Sinjab, Lorena Isabel Gomez-Bolanos, Rossana Lazcano, Alejandra Serrano, Sharia D Hernandez, Enyu Dai, Xuanye Cao, Jian Hu, Minghao Dang, Ruiping Wang, Yanshuo Chu, Xingzhi Song, Jianhua Zhang, Edwin R Parra, Jennifer A Wargo, Stephen G Swisher, Tina Cascone, Boris Sepesi, Andrew P Futreal, Mingyao Li, Steven M Dubinett, Junya Fujimoto, Luisa M Solis Soto, Ignacio I Wistuba, Christopher S Stevenson, Avrum Spira, Shabnam Shalapour, Humam Kadara, Linghua Wang

Faculty, Staff and Student Publications

Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they are poorly characterized. We performed paired single-cell RNA and B-cell receptor (BCR) sequencing of 16 early-stage LUADs and 47 matching multiregion normal tissues. By integrative analysis of ∼50,000 TIBs, we define 12 TIB subsets in the LUAD and adjacent normal ecosystems and demonstrate extensive remodeling of TIBs in LUADs. Memory B cells and plasma cells (PC) were highly enriched in tumor tissues with more differentiated states and increased frequencies of somatic hypermutation. Smokers exhibited markedly elevated PCs and PCs with distinct differentiation trajectories. BCR clonotype diversity …