Medicine and Health Sciences Commons^™

Impact Of Fall Education To Oncology Staff On Oncology Patient Fall Rates, Danni Sloane

Articles, Abstracts, and Reports

Significance & Background

Falls and fall-related injuries impact patients' health outcomes and are the most commonly reported adverse event in hospitals. Patient falls also affect reimbursement rates and can increase length of stay by about 6.3 days and increase undue patient harm. An increase of patients falls on the medical and surgical oncology acute care units have caused undue physical harm, increased moral distress, mental fatigue, and burnout in nurses; as well as placing financial burdens on the healthcare system. Implementing fall education and interventions aligns with national patient safety goals, is a top-priority project, is in alignment with the …

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

Immune-Based Mutation Classification Enables Neoantigen Prioritization And Immune Feature Discovery In Cancer Immunotherapy., Peng Bai, Yongzheng Li, Qiuping Zhou, Jiaqi Xia, Peng-Cheng Wei, Hexiang Deng, Min Wu, Sanny K Chan, John W Kappler, Yu Zhou, Eric Tran, Philippa Marrack, Lei Yin

Articles, Abstracts, and Reports

Genetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the "NP" rule. By integrating this rule with an existing …

Multiplex Immunofluorescence To Measure Dynamic Changes In Tumor-Infiltrating Lymphocytes And Pd-L1 In Early-Stage Breast Cancer., Katherine Sanchez, Isaac Kim, Brie Chun, Joanna Pucilowska, William L. Redmond, Walter Urba, Maritza Martel, Yaping Wu, Mary Campbell, Zhaoyu Sun, Gary Grunkemeier, Shu-Ching Chang, Brady Bernard, David B Page

Articles, Abstracts, and Reports

BACKGROUND: The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents.

METHODS: Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine …

Developing An Enhanced 7-Color Multiplex Ihc Protocol To Dissect Immune Infiltration In Human Cancers., Zhaoyu Sun, Richard Nyberg, Yaping Wu, Brady Bernard, William L. Redmond

Articles, Abstracts, and Reports

The TSA Opal multiplex immunohistochemistry (mIHC) protocol (PerkinElmer) has been used to characterize immune infiltration in human cancers. This technique allows multiple biomarkers to be simultaneously stained in a single tissue section, which helps to elucidate the spatial relationship among individual cell types. We developed and optimized two improved mIHC protocols for a 7-color panel containing 6 biomarkers (CD3, CD8, CD163, PD-L1, FoxP3, and cytokeratin (CK)) and DAPI. The only difference between these two protocols was the staining sequence of those 6 biomarkers as the first sequence is PD-L1/CD163/CD8/CK/CD3/FoxP3/DAPI and the second sequence is FoxP3/CD163/CD8/CK/CD3/PD-L1/DAPI. By comparing PD-L1/FoxP3 staining in …

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.

Nivolumab In Advanced Hepatocellular Carcinoma: Safety Profile And Select Treatment-Related Adverse Events From The Checkmate 040 Study., Karen Julien, Hiu Tung Leung, Carmen Fuertes, Megumi Mori, Miao-Jen Wang, Jocelyn Teo, Lisa Weiss, Sara Hamilton, Holly Difebo, Yoon Jin Noh, Aralee Galway, Jane Koh, Edith Brutcher, Huanyu Zhao, Yun Shen, Marina Tschaika, Yue-Yun To

Articles, Abstracts, and Reports

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.

MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and …