Browsing by Author "Davis, Robert"

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    A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer
    (American Association for Cancer Research, 2023) Veeraraghavan, Jamunarani; Gutierrez, Carolina; De Angelis, Carmine; Davis, Robert; Wang, Tao; Pascual, Tomas; Selenica, Pier; Sanchez, Katherine; Nitta, Hiroaki; Kapadia, Monesh; Pavlick, Anne C.; Galvan, Patricia; Rexer, Brent; Forero-Torres, Andres; Nanda, Rita; Storniolo, Anna M.; Krop, Ian E.; Goetz, Matthew P.; Nangia, Julie R.; Wolff, Antonio C.; Weigelt, Britta; Reis-Filho, Jorge S.; Hilsenbeck, Susan G.; Prat, Aleix; Osborne, C. Kent; Schiff, Rachel; Rimawi, Mothaffar F.; Medicine, School of Medicine
    Purpose: Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-"addicted" tumors who may benefit from a chemotherapy-sparing strategy. Experimental design: Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor-positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based PAM50, and targeted DNA-sequencing. GPA cutoffs and classifier of response were constructed in TBCRC023 using a decision tree algorithm, then validated in PAMELA. Results: In TBCRC023, 72 breast cancer specimens had GPA, PAM50, and sequencing data, of which 15 had pCR. Recursive partitioning identified cutoffs of HER2 ratio ≥ 4.6 and %3+ IHC staining ≥ 97.5%. With PAM50 and sequencing data, the model added HER2-E and PIK3CA wild-type (WT). For clinical implementation, the classifier was locked as HER2 ratio ≥ 4.5, %3+ IHC staining ≥ 90%, and PIK3CA-WT and HER2-E, yielding 55% and 94% positive (PPV) and negative (NPV) predictive values, respectively. Independent validation using 44 PAMELA cases with all three biomarkers yielded 47% PPV and 82% NPV. Importantly, our classifier's high NPV signifies its strength in accurately identifying patients who may not be good candidates for treatment deescalation. Conclusions: Our multiparameter classifier differentially identifies patients who may benefit from HER2-targeted therapy alone from those who need chemotherapy and predicts pCR to anti-HER2 therapy alone comparable with chemotherapy plus dual anti-HER2 therapy in unselected patients.
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    Biorepository and integrative genomics initiative: designing and implementing a preliminary platform for predictive, preventive and personalized medicine at a pediatric hospital in a historically disadvantaged community in the USA
    (Springer Nature, 2018-08) Jose, Rony; Rooney, Robert; Nagisetty, Naga; Davis, Robert; Hains, David; Pediatrics, School of Medicine
    Current healthcare is evolving to emphasize cost-effective care by leveraging results and outcomes of genomic and other advanced research efforts in clinical care and preventive health planning. Through a collaborative effort between the University of Tennessee Health Science Center (UTHSC) and Le Bonheur Children's Hospital (LBCH), the Biorepository and Integrative Genomics (BIG) Initiative was established to set up a pediatric-based DNA biorepository that can serve as a foundation for successful development of delivery platforms for predictive, preventive, and personalized medical services in Memphis, Tennessee, a historically disadvantaged community in the USA. In this paper, we describe the steps that were followed to establish the biorepository. We focused on domains that are essential for implementation of a biorepository for genomic research as an initial goal and identified patient consent, DNA extraction, storage and dissemination, and governance as essential components. Specific needs in each of these domains were addressed by respective solutions developed by multidisciplinary teams under the guidance of a governance model that involved experts from multiple hospital arenas and community members. The end result was the successful launch of a large-scale DNA biorepository, with patient consent greater than 75% in the first year. Our experience highlights the importance of performing pre-design research, needs assessment, and designing an ethically vetted plan that is cost-effective, easy to implement, and inclusive of the community that is served. We believe this biorepository model, with appropriate tailoring according to organizational needs and available resources, can be adopted and successfully applied by other small- to mid-sized healthcare organizations.
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    Incorporating Acupuncture Into American Healthcare: Initiating a Discussion on Implementation Science, the Status of the Field, and Stakeholder Considerations
    (Sage, 2021-08-25) Miller, David W.; Roseen, Eric J.; Stone, Jennifer A.M.; Gardiner, Paula; Olson, Juli; Rosen, Shellie; Wayne, Peter; Davis, Robert; Coeytaux, Remy; Anesthesia, School of Medicine
    Introduction: The field of implementation science is the study of methods that promote the uptake of evidence-based interventions into healthcare policy and practice. While acupuncture has gained significant traction in the American healthcare landscape, its journey has been somewhat haphazard and non-linear. Methods: In June 2019, a group of thirty diverse stakeholders was convened by the Society for Acupuncture Research with the support of a Patient Centered Outcomes Research Institute, Eugene Washington Engagement Award. This group of stakeholders represented a diverse mix of patients, providers, academicians, researchers, funders, allied health professionals, insurers, association leaders, certification experts, and military program developers. The collective engaged in discussion that explored acupuncture's status in healthcare, including reflections on its safety, effectiveness, best practices, and the actual implementation of acupuncture as seen from diverse stakeholder viewpoints. Objectives: A primary goal was to consider how to utilize knowledge from the field of implementation science more systematically and intentionally to disseminate information about acupuncture and its research base, through application of methods known to implementation science. The group also considered novel challenges that acupuncture may present to known implementation processes. Findings: This article summarizes the initial findings of this in-person meeting of stakeholders and the ongoing discussion among the subject matter experts who authored this report. The goal of this report is to catalyze greater conversation about how the field of implementation science might intersect with practice, access, research, and policymaking pertaining to acupuncture. Core concepts of implementation science and its relationship to acupuncture are introduced, and the case for acupuncture as an Evidence Based Practice (EBP) is established. The status of the field and current environment of acupuncture is examined, and the perspectives of four stakeholder groups--patients, two types of professional practitioners, and researchers--are explored in more detail.