Yeonhee Park

• Professor (Assistant) at University of Wisconsin–Madison

Background: Pediatric stroke investigators identified as their top research priority a clinical trial of corticosteroids for focal cerebral arteriopathy (FCA). However, FCA is both rare and an acute condition making it infeasible to enroll the large sample sizes needed for standard, confirmatory clinical trials. We present a pragmatic approach to...

Precision medicine relies on the idea that, for a particular targeted agent, only a subpopulation of patients is sensitive to it and thus may benefit from it therapeutically. In practice, it is often assumed based on preclinical data that a treatment-sensitive subpopulation is known, and moreover that the agent is substantively efficacious in that...

The Phase II clinical trials aim to assess the therapeutic efficacy of a new drug. The therapeutic efficacy has been often quantified by response rate such as overall response rate or survival probability in the Phase II setting. However, there is a strong desire to use survival time, which is the gold standard endpoint for the confirmatory Phase I...

Personalized medicine has been emerging to take into account individual variability in genes and environment. In the era of personalized medicine, it is critical to incorporate the patients’ characteristics and improve the clinical benefit for patients. The patients’ characteristics are incorporated in adaptive randomization to identify patients wh...

In an era of precision medicine, as advanced technology such as molecular profiling at individual patient level has been developed and become increasingly accessible and affordable, biomarker-driven trials have been received a lot of attention and are expected to receive more attention in order to integrate clinical practice with clinical research....

Background: Pulmonary hypertension due to heart failure with preserved ejection fraction (PH HFpEF) is a highly heterogeneous disease associated with right ventricular (RV) failure and adverse outcomes. Current diagnostic tools inadequately characterize pulmonary vascular disease and RV dysfunction, limiting treatment precision. We hypothesized tha...

Background Liquid biopsies in advanced solid tumors can provide a unique noninvasive approach to monitor disease burden over time. Detection and capturing circulating tumor cells (CTCs) in melanoma patients have faced many challenges and limitations. In our study, we use our novel, high-sensitivity, CTC capturing technology to assess numerical hete...

The Mann-Whitney-Wilcoxon test, often referred to as the Mann-Whitney U test or Wilcoxon rank-sum test, is a non-parametric statistical test used to compare two independent groups when the dependent variable is ordinal or continuous but not normally distributed. It’s particularly useful for small sample sizes or when the assumptions of parametric t...

Background: Improved understanding of the high-risk features associated with HFpEF may facilitate risk stratification. Cardiac magnetic resonance (CMR)-based strain and structural data can define detailed myocardial structure, which can be leveraged to define heterogenous HFpEF phenotypes. This study used phenotypic clustering integrating CMR-based...

Background: Highly precise definition of high-risk features associated with HFpEF may guide targeted treatments and inform biological studies. The aim of this two-step study is to 1) define a high risk HFpEF cluster with unsupervised machine learning approach using cardiac magnetic resonance (CMR), 2) define novel pulmonary vascular mechanics at re...

225 Background: ctDNA monitoring has shown promising results in predicting relapse in resected solid tumors. Its role in treatment response assessment and predicting survival outcomes in the unresectable or metastatic disease setting merits further investigation. In our study, we attempt to assess the role of early ctDNA changes in predicting disea...

Dose‐finding studies play a crucial role in drug development by identifying the optimal dose(s) for later studies while considering tolerability. This not only saves time and effort in proceeding with Phase III trials but also improves efficacy. In an era of precision medicine, it is not ideal to assume patient homogeneity in dose‐finding studies a...

The response envelope model proposed by Cook et al. (2010) is an efficient method to estimate the regression coefficient under the context of the multivariate linear regression model. It improves estimation efficiency by identifying material and immaterial parts of responses and removing the immaterial variation. The response envelope model has bee...

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteom...

Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast...

OBJECTIVES/GOALS: Metastasis to regional areas decreases invasive breast cancer (IBC) survival rate by 13%. Despite the clinical importance of lymph node involvement, the role of extracellular matrix (ECM) remodeling in metastases is unknown. We hypothesize that the spatial dysregulation of the collagen proteome facilitates pro-tumorigenic immune i...

Clinical trials play a critical role in drug development which involves a series of phases and requires a significant amount of time and effort. Efficient clinical trial designs are necessary to investigate a new drug. Investigators strongly desire to use the time-to-event endpoint as the primary endpoint for Phase II studies, which evaluates the t...

Neutrophil‐to‐lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil‐to‐eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti‐PD‐1 treated patients with adv...

As a prominent dimension reduction method for multivariate linear regression, the envelope model has received increased attention over the past decade due to its modeling flexibility and success in enhancing estimation and prediction efficiencies. Several enveloping approaches have been proposed in the literature; among these, the partial response...

Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review...

Background An association between lower neutrophil-to-eosinophil ratios (NER) and improved clinical outcomes in patients with metastatic renal cell carcinoma treated with combination ipilimumab/nivolumab (I/N) was recently reported.¹ While neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts have been associated with improved survival in mel...

Background Body mass index (BMI) and serum albumin are common measurements used to evaluate nutritional status. Recent studies have shown conflicting results correlating nutritional status with immune checkpoint inhibitor (ICI) therapy outcomes.1,2 In this study, we investigate if baseline and change in BMI and serum albumin levels correlate with s...

DNA mutations in specific genes can confer preferential benefit from drugs targeting those genes. However, other molecular perturbations can "phenocopy" pathogenic mutations, but would not be identified using standard clinical sequencing, leading to missed opportunities for other patients to benefit from targeted treatments. We hypothesized that RN...

In clinical trials, response-adaptive randomization (RAR) has the appealing ability to assign more subjects to better-performing treatments based on interim results. Traditional RAR strategies alter the randomization ratio on a patient-by-patient basis. An alternate approach is blocked RAR, which groups patients together in blocks and recomputes th...

Immunotherapeutics have revolutionized the treatment of metastatic cancers and are expected to play an increasingly prominent role in the treatment of cancer patients. Recent advances in checkpoint inhibition show promising early results in a number of malignancies, and several treatments have been approved for use. However, the immunotherapeutic a...

Partial least squares (PLS) regression is a popular alternative to ordinary least squares regression because of its superior prediction performance demonstrated in many cases. In various contemporary applications, the predictors include both continuous and categorical variables. A common practice in PLS regression is to treat the categorical variab...

A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and they are diagnosed at a younger age with more advanced tumors with double the rate of lethal, triple negat...

In targeted therapy or immunotherapy, it is common that only a subpopulation of patients are sensitive to and thus may benefit from the therapy. In practice, based on pre-clinical data, it is often assumed that the sensitive subpopulation is known. Subsequent clinical trial data, however, often show that this assumptions is false. We propose a rand...

Background: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. Patients and methods: We conducted a multi-institutional retrospective study, identifying sarco...

A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is not incidence, but aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and are diagnosed at a younger age with more advanced tumors with double the rate of lethal...

PurposeShave margins have been shown to decrease positive final margins in partial mastectomy. We investigated prognostic factors associated with residual disease in shave margins.Methods Patients with invasive breast carcinoma and ductal carcinoma in situ (DCIS) who had circumferential shave margins excised during lumpectomy were abstracted from a...

PurposeTo assess the efficacy of different doses of vitamin D3 on serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone(iPTH), calcium, phosphorus, and alkaline phosphatase concentrations in overweight and obese school-children.MethodsA total of 378 children and adolescents, 6–13 years of age, with age- and sex-specific body mass index(BM...

Background The evolution of pituitary surgery has made it a safe and effective form of treatment; however, risks of inadequate tumor resection, cerebrospinal fluid (CSF) leak, pituitary dysfunction, and vascular injury still exist. The use of intraoperative ultrasonography (IOUS) in pituitary surgery has been well described. Recent advancements in...

Development of cancer screening biomarkers usually follows the Early Detection Research Network 5-Phase guideline in Pepe et al. A key feature of this guide is that the phased development follows a sequential order, moving to the next phase only when the current phase study is complete and has met its target performance. Motivated by a newly funded...

Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies. Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate conten...

The concept of coherence was proposed for single-agent phase I clinical trials to describe the property that a design never escalates the dose when the most recently treated patient has toxicity and never de-escalates the dose when the most recently treated patient has no toxicity. It provides a useful theoretical tool for investigating the propert...

Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Casti...

Background Neuroblastoma (NB) is the most common extracranial solid tumor in infants and children, with amplification of the oncogene MYCN being a hallmark of high‐risk disease and poor prognosis. Although less frequent, overexpression of MYC is similarly an indicator of poor prognosis. Most NB tumors initially respond to chemotherapy, however, mos...

Objectives VitD status is important during pregnancy and lactation as maternal status is linked with fetal and neonatal outcomes: Maternal vitD status during pregnancy predicts neonatal vitD status; similarly, maternal vitD status during lactation predicts infant vitD status as mother is the sole source of vitD to the unsupplemented lactating infan...

Objectives The study aimed to evaluate the feasibility, acceptability, and preliminary clinical impact of BRIGHT (Building a Renewed ImaGe after Head & neck cancer Treatment), a novel telemedicine‐based cognitive‐behavioral intervention to manage body image disturbance (BID) in head and neck cancer (HNC) survivors. Methods HNC survivors with BID w...

Within triple negative breast cancer, several molecular subtypes have been identified, underlying the heterogeneity of such an aggressive disease. The basal-like subtype is characterized by mutations in the TP53 gene, and is associated with a low pathologic complete response rate following neoadjuvant chemotherapy. In a genome-scale short hairpin R...

Background Somatic mutation in TP53 gene (mutp53) is a strong prognostic marker in breast cancer. Triple negative breast cancer (TNBC) is characterized by up to 80% mutp53 and the greatest overall genomic instability among subtypes. Polo-like kinase 1 (PLK1) regulates progression of cells through the G2 phase of the cell cycle. We hypothesize that...

Consider a Bayesian situation in which we observe Y ∼ pθ, where θ ∈ , and we have a family {νh, h ∈ H} of potential prior distributions on . Let g be a real-valued function of θ, and let Ig(h) be the posterior expectation of g(θ) when the prior is νh. We are interested in two problems: (i) selecting a particular value of h, and (ii) estimating the...

Immunotherapy has been hailed as the biggest breakthrough for treating cancer since the first development of chemotherapy. The new features of immunotherapy make the traditional clinical trial paradigm increasingly inefficient and dysfunctional. We propose a Bayesian phase I–II design for immunotherapy trials called BDFIT to find the optimal biolog...

Motivated by searching for associations between genetic variants and brain imaging phenotypes, the aim of this article is to develop a groupwise envelope model for multivariate linear regression in order to establish the association between both multivariate responses and covariates. The groupwise envelope model allows for both distinct regression...

Aims: The purpose of this study was to determine the long-term efficacy and safety of valproic acid (VPA) treatment in patients with pigmentary retinal dystrophies. Methods: A retrospective chart review was conducted on 31 patients with a diagnosis of pigmentary retinal dystrophy prescribed VPA at a single centre. Visual field (VF), visual acuit...