Medicine and Health Sciences Commons^™

Investigation Of The Functional Impact Of Anti-Pd-1 On Tumor-Infiltrating Lymphocytes (Til) And Mapping Of Tumor Genomic Features Relevant For Response To Til Therapy, Caitlin Creasy

Dissertations & Theses (Open Access)

With the growing use of both cellular and antibody-based immunotherapies, it has become more important to uncover biomarkers to predict patient response to therapy and ideally aid in patient selection for specific therapeutics, thereby enhancing treatment outcome. At MD Anderson, we have a 43% response rate to therapy when treating metastatic melanoma patients with adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL), but it is unknown what makes the other 57% of patients not respond to therapy. It is further unknown how particularly early doses of checkpoint inhibitors, like anti-PD-1, attribute to TIL functionality, adding another confounding factor in determining …

Development Of A Ct Metal Artifact Management Algorithm For Proton Therapy Planning (Ampp) For Head And Neck Cancer Patients, Daniela Branco

Dissertations & Theses (Open Access)

Purpose: Dental amalgams (high Z materials) are common sources of artifacts in Head and Neck (HN) images. Commercial artifact reduction techniques have been offered, but many are impractical, produce inaccurate CT images or are not clinically available, thus not widely implemented. The goal of this work is to use CT gantry tilts to develop and evaluate a stereoscopic HN metal artifact management algorithm and investigate its improvement in proton treatment planning.

Methods: The in-house CT metal artifact management method for proton planning (AMPP) uses two angled CT scans to generate a single image set with no metal artifacts posterior …

Investigating The Metabolic Progression Of Glioblastoma With Hyperpolarized Magnetic Resonance, Travis Salzillo

Dissertations & Theses (Open Access)

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma (GBM) can improve patient survival by providing physicians the time to optimally deliver treatment. This includes early in development, while the tumor is still manageable, or following initial therapy, when alternative treatments should be considered. The main goal of this project was to determine whether metabolic imaging with hyperpolarized magnetic resonance spectroscopy (MRS) could detect changes in tumor progression more rapidly than conventional anatomic magnetic resonance imaging (MRI) in patient-derived GBM murine models. To comprehensively capture the dynamic nature of cancer metabolism, in vivo pyruvate-to-lactate conversion with hyperpolarized MRI, …

Assessing Patient Attitudes Toward Genetic Testing For Hereditary Hematologic Malignancy, Addison Johnson

Dissertations & Theses (Open Access)

Since 2003, more than 15 genes have been identified to predispose to hereditary hematologic malignancy (HHM). Although the diagnostic yield of germline analysis for leukemia is similar to solid tumors, referral for genetic evaluation in adults with leukemia is underperformed. Identifying HHM is important for prognostication, treatment, and donor selection for hematopoietic stem cell transplant. No studies have examined leukemia patients’ attitudes toward genetic testing for HHM. This study aimed to assess leukemia patients’ attitudes toward genetic testing and elicit current perceived distress due to a leukemia diagnosis. Data were elicited through an electronic survey sent to 5,513 patients diagnosed …

Modulation Of Pi3k-Akt Pathway In Colorectal Cancer, Maliha Nusrat

Dissertations & Theses (Open Access)

The phosphatidylinositol-3-kinase (PI3K) signaling pathway is activated in 20-40% colorectal cancers (CRC) through PTEN loss (PTEN^loss) and PIK3CA mutations (PIK3CA^mut). Allosteric AKT inhibition with MK2206 monotherapy has been ineffective in CRC patients. We investigated the impact of MK2206 on pharmacodynamic (PD) markers and signaling pathways using reverse phase protein array (RPPA) on (1) paired tumor biopsies from a clinical trial of MK2206 in PI3K-altered metastatic CRC, (2) PTEN^lossCRC patient derived xenografts (PDX) treated with MK2206 or carrier, and (3) MK2206-treated cell lines. PD inhibition was deep in cell lines, less but significant in …

Genetic Counselors' Approaches To Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer, Sarah Burke

Dissertations & Theses (Open Access)

Given the increasing availability of health-related direct-to-consumer genetic testing (DTC-GT) and third-party interpretation (TPI) services, it is likely that genetic counselors (GCs) will continue to encounter consumers that require follow-up counseling for their results. The National Comprehensive Cancer Network recommends clinical-grade genetic testing to confirm commercial results; however, the type of testing that GCs select remains uncharacterized. Therefore, we aimed to describe the specific recommendations that cancer GCs make for confirmatory genetic testing in probands who have already obtained DTC-GT results or TPI data that reported a BRCA1/2 pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered …