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2020

Oncology

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Full-Text Articles in Medicine and Health Sciences

Use Of A Cancer Registry To Evaluate Patient-Reported Outcomes Of Immune Checkpoint Inhibitors., Heather S L Jim, Sarah L Eisel, Aasha I Hoogland, Sandra Shaw, Jennifer C King, Adam P Dicker Dec 2020

Use Of A Cancer Registry To Evaluate Patient-Reported Outcomes Of Immune Checkpoint Inhibitors., Heather S L Jim, Sarah L Eisel, Aasha I Hoogland, Sandra Shaw, Jennifer C King, Adam P Dicker

Department of Radiation Oncology Faculty Papers

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, butfew studies have reported on patient-reported outcomes (PROs) outside the context of a clinicaltrial. The goal of the current study was to assess PROs in participants of a lung cancer registry whohad been treated with an ICI. Patients participating in the GO2Foundation’s Lung Cancer Registrywho reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited toparticipate in a survey about their experiences during treatment. Quality of life was evaluated usingthe Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverseevents were evaluated using an item bank generated for ICIs. Internationally, 226 …


Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar Dec 2020

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …


Identifying Personalized Metabolic Signatures In Breast Cancer., Priyanka Baloni, Wikum Dinalankara, John C Earls, Theo A Knijnenburg, Donald Geman, Luigi Marchionni, Nathan D Price Dec 2020

Identifying Personalized Metabolic Signatures In Breast Cancer., Priyanka Baloni, Wikum Dinalankara, John C Earls, Theo A Knijnenburg, Donald Geman, Luigi Marchionni, Nathan D Price

Articles, Abstracts, and Reports

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino …


Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland J Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon Dec 2020

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland J Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …


Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon Dec 2020

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …


Upfront Treatment Of Flt3-Mutated Aml: A Look Back At The Ratify Trial And Beyond., Gina Keiffer, Kimberly L Aderhold, Neil D Palmisiano Dec 2020

Upfront Treatment Of Flt3-Mutated Aml: A Look Back At The Ratify Trial And Beyond., Gina Keiffer, Kimberly L Aderhold, Neil D Palmisiano

Department of Medical Oncology Faculty Papers

In April 2017, following the results of the RATIFY trial (1), midostaurin, a multikinase FLT3 inhibitor, became the first FDA approved targeted agent for the treatment of acute myeloid leukemia (AML) (2). The addition of midostaurin to standard induction therapy with anthracycline and cytarabine (7 + 3) rapidly became the new standard of care for treatment-naïve, fit patients with FLT3-mutated (FLTmut+) AML (3). More recently, gilteritinib, a selective FLT3 inhibitor, showed superiority to chemotherapy in the treatment of relapsed or refractory FLTmut+ AML (4). With two FLT3 inhibitors now approved by the FDA—that is, the more selective gilteritinib and the …


Development And Preliminary Clinical Activity Of Pd-1-Guided Ctla-4 Blocking Bispecific Dart Molecule., Alexey Berezhnoy, Bradley J Sumrow, Kurt Stahl, Kalpana Shah, Daorong Liu, Jonathan Li, Su-Shin Hao, Anushka De Costa, Sanjeev Kaul, Johanna Bendell, Gregory M Cote, Jason J Luke, Rachel E Sanborn, Manish R Sharma, Francine Chen, Hua Li, Gundo Diedrich, Ezio Bonvini, Paul A Moore Dec 2020

Development And Preliminary Clinical Activity Of Pd-1-Guided Ctla-4 Blocking Bispecific Dart Molecule., Alexey Berezhnoy, Bradley J Sumrow, Kurt Stahl, Kalpana Shah, Daorong Liu, Jonathan Li, Su-Shin Hao, Anushka De Costa, Sanjeev Kaul, Johanna Bendell, Gregory M Cote, Jason J Luke, Rachel E Sanborn, Manish R Sharma, Francine Chen, Hua Li, Gundo Diedrich, Ezio Bonvini, Paul A Moore

Articles, Abstracts, and Reports

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner.


Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian Dec 2020

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …


Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan Dec 2020

Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan

Chemistry Theses and Dissertations

As complex organisms, animals and humans rely on a delicate interplay between many connected systems to maintain proper cellular and whole-body function. Oxygen regulation and homeostasis are vital for proper function in healthy cells, as are core components of aerobic metabolism and efficient ATP generation to supply our energy needs. Maintaining pH homeostasis is also of primary importance; cells maintain pH homeostasis through a host of active and passive transporters to maintain pH balance both inside and outside of the cell.

Events of uncontrolled cellular proliferation, also known as cancer, survive and thrive under conditions that perturb the delicate balance …


Survival Benefit From Immunocheckpoint Inhibitors In Stage Iv Non-Small Cell Lung Cancer Patients With Brain Metastases: A National Cancer Database Propensity-Matched Analysis., Shinkichi Takamori, Takefumi Komiya Md, Emily Powell Dec 2020

Survival Benefit From Immunocheckpoint Inhibitors In Stage Iv Non-Small Cell Lung Cancer Patients With Brain Metastases: A National Cancer Database Propensity-Matched Analysis., Shinkichi Takamori, Takefumi Komiya Md, Emily Powell

PCI Publications and Projects

Immunocheckpoint inhibitors (ICIs) have become a standard pharmacological therapy in non-small cell lung cancer (NSCLC). Because brain metastases (BMs) have historically been listed as exclusion criteria in previous clinical trials involving ICIs in advanced NSCLC, the survival benefit from ICI in NSCLC patients with BMs remains unclear. The National Cancer Database was queried for stage IV NSCLC patients with or without BMs between 2014 and 2015. Overall survival (OS) of stage IV NSCLC patients who received immunotherapy and that of stage IV NSCLC patients who did not receive immunotherapy were compared according to the presence or absence of BMs. Multivariable …


Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu Dec 2020

Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3's lysine …


Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo Dec 2020

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …


Psychological Stress And Cancer: New Evidence Of An Increasingly Strong Link, Rosanna Martinelli Dec 2020

Psychological Stress And Cancer: New Evidence Of An Increasingly Strong Link, Rosanna Martinelli

Translational Medicine @ UniSa

To date stress, a highly complex process that disrupts homeostasis and involves environmental and psychosocial factors, is considered as one of the most crucial factor that affects our daily life, especially urban dweller's life.

Clinical and experimental studies widely support the notion that adrenergic stimulation due to chronic stress affects inflammation and metabolism.

In this work, supported by several recent scientific evidences, we show how stress plays a positive role in cancer initiation, progression and cancer metastasis, a negative role for anti-tumor immune function and therapy response.

Understanding the intricacies of this interaction could provide an additional help on how …


Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan Dec 2020

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in …


Spare Parts Surgery For Oncologic Reconstruction To Preserve Local Advancement Flap For Decubitus Ulcer Reconstruction: A Case Report, Emily Zurbuchen, Nathan Foje, Sean Figy Dec 2020

Spare Parts Surgery For Oncologic Reconstruction To Preserve Local Advancement Flap For Decubitus Ulcer Reconstruction: A Case Report, Emily Zurbuchen, Nathan Foje, Sean Figy

Graduate Medical Education Research Journal

A 58-year-old male presented to our institution with synchronous large left thigh sarcoma and sacral decubitus ulcer requiring oncologic resection and reconstruction. Due to extensive tumor involvement, use of local flap for reconstruction was not feasible. Therefore, a spare parts free fillet flap from the disarticulated lower leg was utilized for reconstruction following oncologic resection. The benefits of this spare parts approach include no donor site morbidity, sufficient tissue padding for later use of prosthesis, and preservation of other flaps for future reconstruction of his sacral decubitus ulcer.


Does Breast Cancer Subtype Impact Margin Status In Patients Undergoing Partial Mastectomy?, Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-Mcnatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric A. Brown, Amanda Mendiola, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen Mcgowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura L. Walters, Tara Mcpartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar Dec 2020

Does Breast Cancer Subtype Impact Margin Status In Patients Undergoing Partial Mastectomy?, Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-Mcnatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric A. Brown, Amanda Mendiola, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen Mcgowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura L. Walters, Tara Mcpartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar

Conference Presentation Abstracts

BACKGROUND: Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy.

METHODS: Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. …


Erratum: Viswanathan, A., Et Al. Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor With Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation)., Anisha Viswanathan, Aliyu Musa, Akshaya Murugesan, João R Vale, Carlos A M Afonso, Saravanan Konda Mani, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu Dec 2020

Erratum: Viswanathan, A., Et Al. Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor With Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation)., Anisha Viswanathan, Aliyu Musa, Akshaya Murugesan, João R Vale, Carlos A M Afonso, Saravanan Konda Mani, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

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Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray Dec 2020

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …


Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel Dec 2020

Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel

Biomedical Sciences

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that …


Dimensions Of Misinformation About The Hpv Vaccine On Instagram: Content And Network Analysis Of Social Media Characteristics., Philip M. Massey, Matthew D. Kearney, Michael K. Hauer, Preethi Selvan, Emmanuel Koku, Amy Leader Dec 2020

Dimensions Of Misinformation About The Hpv Vaccine On Instagram: Content And Network Analysis Of Social Media Characteristics., Philip M. Massey, Matthew D. Kearney, Michael K. Hauer, Preethi Selvan, Emmanuel Koku, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram.

OBJECTIVE: The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine …


Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl Dec 2020

Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl

Department of Medical Oncology Faculty Papers

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent …


Bystanders’ Perspectives On The Provision Of Informal, Hospital-Based Care To Bedridden Patients With Cancer In Sri Lanka, B. Sunil S. De Silva Dec 2020

Bystanders’ Perspectives On The Provision Of Informal, Hospital-Based Care To Bedridden Patients With Cancer In Sri Lanka, B. Sunil S. De Silva

Nursing ETDs

Due to the nursing shortage in Sri Lanka, patients need informal caregivers, known as bystanders, to help provide patient care. This study described bystanders’ perspectives on informal, hospital-based care to bedridden patients with cancer in Sri Lanka. In this qualitative descriptive study, 17 bystanders at Apeksa/Cancer Hospital, Sri Lanka, were recruited using snowballing sampling. Data were collected through telephone interviews and analyzed using content and thematic analyses. Findings showed that paid and unpaid bystanders cover all caregiving tasks with minimum interaction with nurses. Unpaid bystanders described the need for same-sex bystanders and additional help with patients’ mobilization and specialized care. …


Burden Of Care As Perceived By Informal Caregivers Of The Patients Receiving Chemotherapy In Tertiary Care Hospital Of Karachi, Pakistan, Asher Ghori, Rubina Barolia, Naghma Rizvi, Ghulam Qadir Dec 2020

Burden Of Care As Perceived By Informal Caregivers Of The Patients Receiving Chemotherapy In Tertiary Care Hospital Of Karachi, Pakistan, Asher Ghori, Rubina Barolia, Naghma Rizvi, Ghulam Qadir

School of Nursing & Midwifery

Background: Almost 32.5 million people are diagnosed with cancer annually. The huge number of cancer patients with deteriorating health renders a far greater number of informal caregivers bearing the burden of care in different forms and magnitude. The main purpose of the study was to explore the types of burden perceived by the informal caregivers and the factors associated with the caregiving burden.
Methods: A quantitative descriptive cross-sectional study design was adopted to answer the research questions from April to May 2016. Around 200 informal caregivers were recruited from one of the tertiary hospitals of Karachi, Pakistan. The modified ZBIS …


Improving Code Response Time Through Strategic Positioning Of Nursing House Supervisors: Results Of A Nurse-Led Intervention, Noah R. Zanville, Paula T. Smith, Albis A. Aguiar, Joan Simon-Smith, Jessenia Menendez, Alice J. Cockerel, Rosalina P. Butao, Marguerite Rowell Dec 2020

Improving Code Response Time Through Strategic Positioning Of Nursing House Supervisors: Results Of A Nurse-Led Intervention, Noah R. Zanville, Paula T. Smith, Albis A. Aguiar, Joan Simon-Smith, Jessenia Menendez, Alice J. Cockerel, Rosalina P. Butao, Marguerite Rowell

Nursing & Health Sciences Research Journal

Background: In many settings, the nursing house supervisors (NHS) are a critical part of the entity’s code response team. To date, much of the research on code response has focused on improving response times through staff-focused interventions such as simulation training. However, use of data to determine where to physically place NHS in the building to optimize code response times has received little attention, especially in an outpatient oncology setting.

Purpose: To test whether using data on code frequency/location to strategically position NHS could reduce mean code response times in large (450,000-ft2) outpatient cancer center.

Methods: Data on code volume, …


Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu Dec 2020

Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational …


A Phase Ii Study Of The Insulin-Like Growth Factor Type I Receptor Inhibitor Imc-A12 In Patients With Metastatic Uveal Melanoma., Jane Mattei, Alexej Ballhausen, Roland Bassett, Michael Shephard, Chandrani Chattopadhyay, Courtney Hudgens, Michael Tetzlaff, Scott Woodman, Takami Sato, Sapna P Patel Dec 2020

A Phase Ii Study Of The Insulin-Like Growth Factor Type I Receptor Inhibitor Imc-A12 In Patients With Metastatic Uveal Melanoma., Jane Mattei, Alexej Ballhausen, Roland Bassett, Michael Shephard, Chandrani Chattopadhyay, Courtney Hudgens, Michael Tetzlaff, Scott Woodman, Takami Sato, Sapna P Patel

Department of Medical Oncology Faculty Papers

Uveal melanoma is a rare and aggressive malignancy and up to half of all patients will develop metastatic disease despite the effective treatment of the primary tumor. Insulin-like growth factors I/II play a fundamental role in the cell migration, proliferation, and apoptosis. IMC-A12, a mAb specifically targets insulin-like growth factor type I receptor, has shown promise in preclinical studies. We performed a multicenter phase II study for patients with metastatic uveal melanoma administered IMC-A12 10 mg/kg IV every two weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response (proportion of patients with complete or partial response), …


Sitc Cancer Immunotherapy Resource Document: A Compass In The Land Of Biomarker Discovery., Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean-Charles J B Grivel, Sumati Gupta, Brent A Hanks, Sylvia Janetzki, Thomas O Kleen, Yoshinobu Koguchi, Amanda W Lund, Cristina Maccalli, Yolanda D Mahnke, Ruslan D Novosiadly, Senthamil R Selvan, Tasha Sims, Yingdong Zhao, Holden T Maecker Dec 2020

Sitc Cancer Immunotherapy Resource Document: A Compass In The Land Of Biomarker Discovery., Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean-Charles J B Grivel, Sumati Gupta, Brent A Hanks, Sylvia Janetzki, Thomas O Kleen, Yoshinobu Koguchi, Amanda W Lund, Cristina Maccalli, Yolanda D Mahnke, Ruslan D Novosiadly, Senthamil R Selvan, Tasha Sims, Yingdong Zhao, Holden T Maecker

Articles, Abstracts, and Reports

Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in …


Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume Ii-Practical Challenges., Alessandra Cesano, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Sergio Rutella Dec 2020

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume Ii-Practical Challenges., Alessandra Cesano, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Sergio Rutella

Articles, Abstracts, and Reports

The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated …


A Rare Case Of Idiopathic Pyometra In A Premenopausal Patient., Kristina M Mori, Howard D Epstein, Michael C Roossin, Bram H Goldstein Dec 2020

A Rare Case Of Idiopathic Pyometra In A Premenopausal Patient., Kristina M Mori, Howard D Epstein, Michael C Roossin, Bram H Goldstein

Articles, Abstracts, and Reports

Pyometra is a very uncommon disease principally occurring in postmenopausal women. It is characterized by the accumulation of purulent material within the uterine cavity. This paper presents the clinical history of a 35-year-old premenopausal woman with otherwise normal menstruation who developed heavy menstruation and was diagnosed with a benign pyometra of indeterminate etiology in March 2017. The patient underwent repeated ultrasound-guided drainage, dilation and curettage, and antibiotic therapy. Biopsies of the pelvic sidewall revealed endometriosis in June 2017. The heavy menstruation and suppurative fluid in the uterus of the patient persisted in which intramuscular leuprolide acetate was prescribed to address …


Target Treatment With Stereotactic Radiation For Recurrent Gliomas, Ayesha Ali, Victor E. Chen, Claire Zurlo, James M Taylor, Christian Fernandez, Wenyin Shi Dec 2020

Target Treatment With Stereotactic Radiation For Recurrent Gliomas, Ayesha Ali, Victor E. Chen, Claire Zurlo, James M Taylor, Christian Fernandez, Wenyin Shi

Department of Radiation Oncology Faculty Papers

High grade gliomas (HGG) have a propensity to recur locally and have poor outcomes. As such, safe and effective treatment is paramount. Target treatment with stereotactic radiation allows safe re-irradiation through minimizing normal brain tissue radiation due to its high precision. In this review, we evaluated the clinical experiences using SRS and FSRT for re-irradiation in HGG. We report the radiobiological advantages and disadvantages of both modalities as well as the safety and efficacy published in current literature.