Biomedical Informatics Commons^™

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Diverse Clonal Fates Emerge Upon Drug Treatment Of Homogeneous Cancer Cells, Yogesh Goyal, Gianna T Busch, Maalavika Pillai, Jingxin Li, Ryan H Boe, Emanuelle I Grody, Manoj Chelvanambi, Ian P Dardani, Benjamin Emert, Nicholas Bodkin, Jonas Braun, Dylan Fingerman, Amanpreet Kaur, Naveen Jain, Pavithran T Ravindran, Ian A Mellis, Karun Kiani, Gretchen M Alicea, Mitchell E Fane, Syeda Subia Ahmed, Haiyin Li, Yeqing Chen, Cedric Chai, Jessica Kaster, Russell G Witt, Rossana Lazcano, Davis R Ingram, Sarah B Johnson, Khalida Wani, Margaret C Dunagin, Alexander J Lazar, Ashani T Weeraratna, Jennifer A Wargo, Meenhard Herlyn, Arjun Raj

Faculty, Staff and Student Publications

Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1-7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7-9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and …

Mesothelin-Targeting T Cell Receptor Fusion Construct Cell Therapy In Refractory Solid Tumors: Phase 1/2 Trial Interim Results, Raffit Hassan, Marcus Butler, Roisin E O'Cearbhaill, David Y Oh, Melissa Johnson, Kevin Zikaras, Munisha Smalley, Michael Ross, Janos L Tanyi, Azam Ghafoor, Nirali N Shah, Babak Saboury, Liang Cao, Alfonso Quintás-Cardama, David Hong

Faculty, Staff and Student Publications

The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of …

Artificial Mirnas Derived From Mir-181 Family Members Have Potential In Cancer Therapy Due To An Altered Spectrum Of Target Mrnas, Sergiu Chira, Cristina Ciocan, Cecilia Bica, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

miRNAs are a class of noncoding RNAs with gene regulation properties, and they function as key factors in cell homeostasis. The interaction of miRNAs with their target mRNAs is largely considered to rely on sequence complementarity; however, some evidence indicates that mature miRNAs can adopt diverse conformations with implications for their function. Using the oncogenic miR-181 family as a study model, we suggest that a potential relationship between the primary sequence and secondary structure of miRNAs may have an impact on the number and spectrum of targeted cellular transcripts. We further emphasize that specific alterations in miR-181 primary sequences might …

Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit

Faculty, Staff and Student Publications

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …

Cardiac Substructure Radiation Dose And Risk Of Late Cardiac Disease In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, James E Bates, Suman Shrestha, Qi Liu, Susan A Smith, Daniel A Mulrooney, Wendy Leisenring, Todd Gibson, Leslie L Robison, Eric J Chow, Kevin C Oeffinger, Gregory T Armstrong, Louis S Constine, Bradford S Hoppe, Choonsik Lee, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

PURPOSE: Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.

METHODS: Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.

RESULTS: The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 …

Association Of Patient-Reported Health-Related Quality Of Life With Physician-Reported Toxicities In Adolescents And Young Adults Receiving Radiation Therapy For Cancer, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

PURPOSE: Radiation therapy (RT) may cause toxicities in adolescents and young adults (AYAs, age 15-39 years) with cancer. However, the range of RT-related toxicities in AYAs and the affect on health-related quality of life (HRQOL) has not been well studied. We performed a cross-sectional study in AYAs with cancer who received RT to identify RT-related toxicities and examine their impact on HRQOL.

MATERIALS AND METHODS: A total of 178 AYAs received RT and completed PROMIS HRQOL instruments from 2018 to 2022. Acute and late physician-graded Common Terminology Criteria for Adverse Events RT-related toxicities were extracted and described. Multivariable linear regression …

Cooperative Activation Of Pdk1 And Akt By Mapk4 Enhances Cancer Growth And Resistance To Therapy, Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang

Faculty, Staff and Students Publications

Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase of the protein A, G, and C (AGC) family kinases that play important roles in regulating cancer cell proliferation, survival, and metabolism. Besides phosphorylating/activating AKT at the cell membrane in a PI3K-dependent manner, PDK1 also exhibits constitutive activity on many other AGC kinases for tumor-promoting activity. In the latter case, PDK1 protein levels dominate its activity. We previously reported that MAPK4, an atypical MAPK, can PI3K-independently promote AKT activation and tumor growth. Here, using triple-negative breast cancer (TNBC) cell models, we demonstrate that MAPK4 can also enhance PDK1 protein synthesis, thus phosphorylate/activate PDK1 …

The New World Of Rna Diagnostics And Therapeutics, Giovanni Blandino, Roberto Dinami, Marco Marcia, Eleni Anastasiadou, Brid M Ryan, Alina Catalina Palcau, Luigi Fattore, Giulia Regazzo, Rosanna Sestito, Rossella Loria, Ana Belén Díaz Méndez, Maria Chiara Cappelletto, Claudio Pulito, Laura Monteonofrio, George A Calin, Gabriella Sozzi, Jit Kong Cheong, Ranit Aharonov, Gennaro Ciliberto

Faculty, Staff and Student Publications

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27-28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled "The New World of RNA diagnostics and therapeutics" highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.This report collected the presentations …

Analysis Of Performance And Failure Modes Of The Iroc Proton Liver Phantom, Hunter Mehrens, Paige Taylor, Paola Alvarez, Stephen Kry

Faculty, Staff and Student Publications

Purpose: To analyze trends in institutional performance and failure modes for the Imaging and Radiation Oncology Core’s (IROC’s) proton liver phantom.

Materials and Methods: Results of 66 phantom irradiations from 28 institutions between 2015 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom results. Phantom results included pass/fail classification, average thermoluminescent dosimeter (TLD) ratio of both targets, and percentage of pixels passing gamma of both targets. The following categories were evaluated in terms of how they predicted these outcomes: irradiation year, treatment planning system (TPS), TPS algorithm, treatment machine, number …

Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness

Faculty, Staff and Student Publications

Purpose: Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality.

Methods: CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and …

Feasibility And Safety Of Personalized, Multi-Target, Adoptive Cell Therapy (Ima101): First-In-Human Clinical Trial In Patients With Advanced Metastatic Cancer, Apostolia M Tsimberidou, Kerstin Guenther, Borje S Andersson, Regina Mendrzyk, Amir Alpert, Claudia Wagner, Anna Nowak, Katrin Aslan, Arun Satelli, Fabian Richter, Sabrina Kuttruff-Coqui, Oliver Schoor, Jens Fritsche, Zoe Coughlin, Ali S Mohamed, Kerry Sieger, Becky Norris, Rita Ort, Jennifer Beck, Henry Hiep Vo, Franziska Hoffgaard, Manuel Ruh, Linus Backert, Ignacio I Wistuba, David Fuhrmann, Nuhad K Ibrahim, Van Karlyle Morris, Bryan K Kee, Daniel M Halperin, Graciela M Nogueras-Gonzalez, Partow Kebriaei, Elizabeth J Shpall, David Vining, Patrick Hwu, Harpreet Singh, Carsten Reinhardt, Cedrik M Britten, Norbert Hilf, Toni Weinschenk, Dominik Maurer, Steffen Walter

Faculty, Staff and Student Publications

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with …

The Swi/Snf Chromatin-Remodeling Subunit Dpf2 Facilitates Nrf2-Dependent Antiinflammatory And Antioxidant Gene Expression, Gloria Mas, Na Man, Yuichiro Nakata, Concepcion Martinez-Caja, Daniel Karl, Felipe Beckedorff, Francesco Tamiro, Chuan Chen, Stephanie Duffort, Hidehiro Itonaga, Adnan K Mookhtiar, Kranthi Kunkalla, Alfredo M Valencia, Clayton K Collings, Cigall Kadoch, Francisco Vega, Scott C Kogan, Ramin Shiekhattar, Lluis Morey, Daniel Bilbao, Stephen D Nimer

Faculty, Staff and Student Publications

During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation. DPF2 is a defining subunit of the hematopoiesis-specific BAF (SWI/SNF) chromatin-remodeling complex, and it is mutated in multiple cancers and neurological disorders. We uncovered that hematopoiesis-specific Dpf2-KO mice developed leukopenia, severe anemia, and lethal systemic inflammation characterized by histiocytic and fibrotic tissue infiltration resembling a …

Associations Between Kir/Kir-Ligand Genotypes And Clinical Outcome For Patients With Advanced Solid Tumors Receiving Bempeg Plus Nivolumab Combination Therapy In The Pivot-02 Trial, A S Feils, A K Erbe, J Birstler, K Kim, U Hoch, S L Currie, T Nguyen, D Yu, A O Siefker-Radtke, N Tannir, S M Tolaney, A Diab, P M Sondel

Faculty, Staff and Student Publications

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with …

Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions, Alex K Bryant, Zoey Chopra, Donna M Edwards, Adam S Whalley, Brian G Bazzell, Julie A Moeller, Michael J Kelley, A Mark Fendrick, Eve A Kerr, Nithya Ramnath, Michael D Green, Timothy P Hofer, Garth W Strohbehn

Faculty, Staff and Student Publications

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at "one-size-fits-all" flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug …

The Promise And Future Of Radiomics For Personalized Radiotherapy Dosing And Adaptation, Rachel B Ger, Lise Wei, Issam El Naqa, Jing Wang

Faculty, Staff and Student Publications

Quantitative image analysis, also known as radiomics, aims to analyze large-scale quantitative features extracted from acquired medical images using hand-crafted or machine-engineered feature extraction approaches. Radiomics has great potential for a variety of clinical applications in radiation oncology, an image-rich treatment modality that utilizes computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for treatment planning, dose calculation, and image guidance. A promising application of radiomics is in predicting treatment outcomes after radiotherapy such as local control and treatment-related toxicity using features extracted from pretreatment and on-treatment images. Based on these individualized predictions of treatment outcomes, radiotherapy …

Characteristics, Treatment, And Outcome Of Diverticulitis After Immune Checkpoint Inhibitor Treatment In Patients With Malignancies, Austin R Thomas, Mostafa Eyada, Miho Kono, Krishnavathana Varatharajalu, Yang Lu, Guofan Xu, Kavea Panneerselvam, Malek Shatila, Mehmet Altan, Jennifer Wang, John A Thompson, Hao Chi Zhang, Muhammad Ali Khan, Gottumukkala S Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Purpose: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment.

Methods: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups.

Results: 77 eligible patients were included: 63 patients developed …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Tumor And Breast Activity Concentrations, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of

PURPOSE: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue

METHODS: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of …

G Protein-Coupled Receptor-Targeting Antibody-Drug Conjugates: Current Status And Future Directions, Peyton High, Kendra S Carmon

Faculty, Staff and Student Publications

In recent years, antibody-drug conjugates (ADCs) have emerged as promising anti-cancer therapeutic agents with several having already received market approval for the treatment of solid tumor and hematological malignancies. As ADC technology continues to improve and the range of indications treatable by ADCs increases, the repertoire of target antigens has expanded and will undoubtedly continue to grow. G protein-coupled receptors (GPCRs) are well-characterized therapeutic targets implicated in many human pathologies, including cancer, and represent a promising emerging target of ADCs. In this review, we will discuss the past and present therapeutic targeting of GPCRs and describe ADCs as therapeutic modalities. …

Slc7a11 Expression Level Dictates Differential Responses To Oxidative Stress In Cancer Cells, Yuelong Yan, Hongqi Teng, Qinglei Hang, Lavanya Kondiparthi, Guang Lei, Amber Horbath, Xiaoguang Liu, Chao Mao, Shiqi Wu, Li Zhuang, M James You, Masha V Poyurovsky, Li Ma, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H2O2, a common oxidative stress inducer, its high overexpression dramatically increases H2O2-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H2O2 treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). We further show …

Eganelisib, A First-In-Class Pi3kγ Inhibitor, In Patients With Advanced Solid Tumors: Results Of The Phase 1/1b Mario-1 Trial, David S Hong, Michael Postow, Bartosz Chmielowski, Ryan Sullivan, Amita Patnaik, Ezra E W Cohen, Geoffrey Shapiro, Conor Steuer, Martin Gutierrez, Heather Yeckes-Rodin, Robert Ilaria, Brenda O'Connell, Joanna Peng, Guangbin Peng, Nora Zizlsperger, Anthony Tolcher, Jedd D Wolchok

Faculty, Staff and Student Publications

Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.

Patients and methods: Dose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE).

Results: …

Genome-Wide Analyses Characterize Shared Heritability Among Cancers And Identify Novel Cancer Susceptibility Regions, Sara Lindström, Lu Wang, Helian Feng, Arunabha Majumdar, Sijia Huo, James Macdonald, Tabitha Harrison, Constance Turman, Hongjie Chen, Nicholas Mancuso, Theo Bammler, Breast Cancer Association Consortium (Bcac), Steve Gallinger, Stephen B Gruber, Marc J Gunter, Loic Le Marchand, Victor Moreno, Kenneth Offit, Colorectal Transdisciplinary Study (Corect), Colon Cancer Family Registry Study (Ccfr), Genetics And Epidemiology Of Colorectal Cancer Consortium (Gecco), Immaculata De Vivo, Tracy A O'Mara, Amanda B Spurdle, Ian Tomlinson, Endometrial Cancer Association Consortium (Ecac), Rebecca Fitzgerald, Puya Gharahkhani, Ines Gockel, Janusz Jankowski, Stuart Macgregor, Johannes Schumacher, Jill Barnholtz-Sloan, Melissa L Bondy, Richard S Houlston, Robert B Jenkins, Beatrice Melin, Margaret Wrensch, Paul Brennan, David C Christiani, Mattias Johansson, James Mckay, Melinda C Aldrich, Christopher I Amos, Maria Teresa Landi, Adonina Tardon, International Lung Cancer Consortium (Ilcco), D Timothy Bishop, Florence Demenais, Alisa M Goldstein, Mark M Iles, Peter A Kanetsky, Matthew H Law, Ovarian Cancer Association Consortium (Ocac), Laufey T Amundadottir, Rachael Stolzenberg-Solomon, Brian M Wolpin, Pancreatic Cancer Cohort Consortium (Panscan), Alison Klein, Gloria Petersen, Harvey Risch, Pancreatic Cancer Case-Control Consortium (Panc4), The Practical Consortium, Stephen J Chanock, Mark P Purdue, Ghislaine Scelo, Paul Pharoah, Siddhartha Kar, Rayjean J Hung, Bogdan Pasaniuc, Peter Kraft

Faculty, Staff and Student Publications

BACKGROUND: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.

METHODS: We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel …

Learning Through Doing: Comprehensive Programming For A Training Program In Cancer Disparities, Kayce D Solari Williams, Kamisha Hamilton Escoto, Crystal Roberson, Kathy Le, Lorraine R Reitzel, Lorna H Mcneill, Shine Chang

Faculty, Staff and Student Publications

In the United States, preparing researchers and practitioners for careers in cancer requires multiple components for success. In this reflection article, we discuss our approach to designing a comprehensive research training program in cancer disparities. We focused on elements that provide students and early career scientists a deep understanding of disparities through first-hand experiences and skills training necessary to build a research career in the area. Our Educational Program sits within the framework of an NCI P20 program, "UHAND (University of Houston/MD Anderson Cancer Center)", jointly established by an NCI-designated comprehensive cancer center and a minority-serving university as a collaborative …

Piloting The Sexual And Gender Minority Cancer Curricular Advances For Research And Education (Sgm Cancer Care) Workshop: Research Training In The Service Of Sgm Cancer Health Equity, Miria Kano, Irene Tamí-Maury, Mandi L Pratt-Chapman, Shine Chang, Mikaela Kosich, Gwendolyn P Quinn, Tonia Poteat, Peter A Kanetsky, Ronit Elk, Ulrike Boehmer, Julian Sanchez, Charles Kamen, Nelson F Sanchez

Faculty, Staff and Student Publications

The purpose of this study is to describe the context, curriculum design, and pilot evaluation of the educational program "Sexual and Gender Minority Cancer Curricular Advances for Research and Education" (SGM Cancer CARE), a workshop for early-career researchers and healthcare providers interested in gaining knowledge and skills in sexual and gender minority (SGM) cancer research and healthcare advocacy. A needs assessment of a sample of clinicians and researchers (n = 104) and feedback from an Advisory Board informed the curriculum design of the SGM Cancer CARE workshop. Four SGM-tailored modules, focusing on epidemiology, clinical research, behavioral science and interventions, and …

A Highly Selective Humanized Ddr1 Mab Reverses Immune Exclusion By Disrupting Collagen Fiber Alignment In Breast Cancer, Junquan Liu, Huai-Chin Chiang, Wei Xiong, Victor Laurent, Samuel C Griffiths, Jasmin Dülfer, Hui Deng, Xiujie Sun, Y Whitney Yin, Wenliang Li, Laurent P Audoly, Zhiqiang An, Thomas Schürpf, Rong Li, Ningyan Zhang

Faculty, Staff and Student Publications

BACKGROUND: Immune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.

METHODS: To develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding …

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …

Integration Of Remote Symptom And Biometric Monitoring Into The Care Of Adult Patients With Cancer Receiving Chemotherapy-A Decentralized Feasibility Pilot Study, Anaeze C Offodile, Domenica Delgado, Yu-Li Lin, Danielle Geyen, Christopher J Miller, Sanchita Jain, Janice P Finder, Sanjay Shete, Frank V Fossella, Michael J Overman, Susan K Peterson

Faculty, Staff and Student Publications

PURPOSE: Although electronic patient-reported outcomes (ePROs) are efficacious in symptom management, much is unknown about the utility of vital signs surveillance. We examined the feasibility of a remote patient monitoring platform that integrates ePROs and biometrics into the ambulatory management of symptom burden.

METHODS: Using a decentralized workflow, patients with gastrointestinal or thoracic cancer were approached for a 1-month study. Patients reported symptom burden via ePROs and biometrics (blood pressure, oxygen saturation, pulse, weight, and temperature) using bluetooth-enabled devices daily. Alerts on the basis of prespecified thresholds were managed via nurse-led triage. Adherence was defined as the completion of > 70% …

Five-Year Overall Survival With Ipilimumab And Stereotactic Ablative Radiotherapy For Metastatic Disease, Kewen He, David S Hong, Chad Tang, Duygu Sezen, Livia Cox, Aurian Maleki, Genevieve Bertolet, Quynh-Nhu Nguyen, Nathan I Comeaux, Lily Schuda, Dawei Chen, James W Welsh

Faculty, Staff and Student Publications

Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900).

Methods and materials: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy …

Cumulative Burden Of Late, Major Surgical Intervention In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study (Ccss) Cohort, Bryan V Dieffenbach, Andrew J Murphy, Qi Liu, Duncan C Ramsey, Erik J Geiger, Lisa R Diller, Rebecca M Howell, Kevin C Oeffinger, Leslie L Robison, Yutaka Yasui, Gregory T Armstrong, Eric J Chow, Brent R Weil, Christopher B Weldon

Faculty, Staff and Student Publications

Background: Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions.

Methods: We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in …

Learning Through Doing: Comprehensive Programming For A Training Program In Cancer Disparities, Kayce D Solari Williams, Kamisha Hamilton Escoto, Crystal Roberson, Kathy Le, Lorraine R Reitzel, Lorna H Mcneill, Shine Chang

Faculty, Staff and Student Publications

In the United States, preparing researchers and practitioners for careers in cancer requires multiple components for success. In this reflection article, we discuss our approach to designing a comprehensive research training program in cancer disparities. We focused on elements that provide students and early career scientists a deep understanding of disparities through first-hand experiences and skills training necessary to build a research career in the area. Our Educational Program sits within the framework of an NCI P20 program, "UHAND (University of Houston/MD Anderson Cancer Center)", jointly established by an NCI-designated comprehensive cancer center and a minority-serving university as a collaborative …