André Rogatko

André Rogatko
Independent Scientist

Ph.D.

About

224
Publications
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Introduction

Publications

Publications (224)
Article
Background: There has been limited evaluation of health-related quality of life (HRQOL) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. HRQOL outcomes in the National Surgical Adjuvant Breast and Bowel Project R-04 trial are examined in this article. Methods: Between 2004 and 2010, R-04 patients were invited to enroll in the H...
Article
Full-text available
Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues—such as incomplete mechanistic knowledge an...
Preprint
Ischemic stroke is a leading cause of death worldwide, but there has been little success translating putative cerebroprotectants from preclinical trials to patients. We investigated computational image-based assessment tools for practical improvement of the quality, scalability, and outlook for large scale preclinical screening for potential therap...
Preprint
Rodent stroke models are important for evaluating treatments and understanding the pathophysiology and behavioral changes of brain ischemia, and magnetic resonance imaging (MRI) is a valuable tool for measuring outcome in preclinical studies. Brain extraction is an essential first step in most neuroimaging pipelines; however, it can be challenging...
Article
Background: Chemotherapy-induced toxicities are prevalent in patients treated with adjuvant chemotherapy and often impact on activities of daily living and other aspects of function and well-being. Understanding which patients are more likely to experience long-term chemotherapy-induced peripheral neuropathy (CIPN) and hot flashes may help tailor t...
Article
Full-text available
Background Graphical displays and data visualization are essential components of statistical analysis that can lead to improved understanding of clinical trial adverse event (AE) data. Correspondence analysis (CA) has been introduced decades ago as a multivariate technique that can communicate AE contingency tables using two-dimensional plots, whil...
Article
A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggress...
Chapter
We discuss several innovative phase I and phase I–II designs for early phase cancer clinical trial with drug combinations focusing on continuous dose levels of both agents. For phase I trials with drug combinations, the main objective is to estimate the maximum tolerated dose (MTD) curve in the two-dimensional Cartesian plane. A parametric model is...
Article
PURPOSE The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastroz...
Article
Full-text available
Objective To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer. Methods Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3–6 and as maintenance monotherapy in...
Article
Purpose: The toxicity index (TI) is a summary index that accounts for toxicity grades associated with cancer symptoms that is more sensitive than other toxicity systems to treatment differences. The TI can be used with patient-reported symptoms but requires that scores for different items represent equivalent severity. The purpose of this article...
Article
e17008 Background: A morphological subset of prostate cancer (PCa) circulating tumor cells (CTCs) with particularly small nuclei (< 8.5 μm), named very-small-nuclear CTCs (vsnCTCs), were found to be correlated with the presence of visceral metastases. It is reported that the depletion of nuclear envelope protein emerin promotes PCa metastasis and i...
Article
Importance Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years we...
Article
BACKGROUND: Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life (QoL) and resource consumption. Yet, guidelines focus on symptom management while clinical pr...
Article
167 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PCa). Previously, a subgroup of PCa CTCs, with particularly small nuclei ( < 8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We hy...
Article
Full-text available
PURPOSE Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. A...
Preprint
We propose to apply stacked CA using contribution biplots as a tool to explore differences in AE data among treatments in clinical trials. We defined five levels of refinement for the analysis based on data derived from the Common Terminology Criteria for Adverse Events (CTCAE) grades, domains, terms and their combinations. In addition, we develope...
Article
Full-text available
Cancer clinical trials typically generate detailed patient toxicity data. The most common measure used to summarize patient toxicity is the maximum grade among all toxicities and it does not fully represent the toxicity burden experienced by patients. In this article, we study the mathematical and statistical properties of the toxicity index (TI),...
Conference Paper
Background: Current risk stratification models in prostate cancer (PC) have been based on clinical and pathological variables. Beyond serum prostate-specific antigen (PSA) concentration measurements, there remain few new biomarkers to help identify patients at risk for poor clinical outcomes. Morphological analyses using Gleason scoring along with...
Article
Full-text available
Objectives Prostate cancer (PC) is the most common non-skin cancer in men and the second leading cause of cancer death. Omega-3 fatty acids and polyphenols have bioactive properties that may alter tumor biology and reduce PC progression. Walnuts (Juglans regia L.) are one of the best sources of plant-based omega-3 s (2.5 g per oz) and polyphenols (...
Conference Paper
e17512 Background: Very-small-nuclear circulating tumor cells (vsnCTCs) as a subset of CTCs with nuclear size < 8.5 μm associated with visceral metastases (VM) in advanced metastatic, castration-resistant prostate cancer (mCRPC). As VM predicts foreshortened survival, we hypothesized that vsnCTCs would be directly associated with poor overall survi...
Article
Background: The National Cancer Institute Moonshot℠ research initiative calls for improvements in the analysis and reporting of treatment toxicity to advise key stakeholders on treatment tolerability and inform regulatory and clinical decision-making. This study illustrates alternative approaches to toxicity evaluation using the National Surgical A...
Article
Full-text available
Background: The National Cancer Institute Moonshot℠ research initiative calls for improvements in the analysis and reporting of treatment toxicity to advise key stakeholders on treatment tolerability and inform regulatory and clinical decision-making. This study illustrates alternative approaches to toxicity evaluation using the National Surgical...
Conference Paper
168 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We propos...
Conference Paper
726 Background: Unintentional weight loss affecting > 85% of pancreatic cancer (PC) patients contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Optimal treatment approaches have not been developed. We hypothesize that peptide-based enteral nutritional support in cachectic advanced PC patients, receiving pallia...
Article
Full-text available
Background: Stress cardiac magnetic resonance (CMR) imaging with myocardial perfusion reserve index (MPRI) measurement has emerged as a noninvasive method for assessing coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD). Pharmacologic stress with adenosine or regadenoson is typically used with compa...
Article
Full-text available
We performed a Ph2 trial in adults and children to test abatacept for AGVHD prevention (‘ABA2’, Clinicaltrials # NCT01743131), based on our promising preclinical and pilot patient data. ABA2 had 2 cohorts: A) HLA-mismatched (‘7/8’, n = 43), a single-arm study with pre-specified CIBMTR matched analysis (vs CNI+MTX or CNI+MTX+ATG). B) HLA-matched (‘8...
Article
Backgroud: Immue-based therapy for metastatic breast cacer has had limited success, particularly i molecular subtypes with low somatic mutatios rates. Strategies to augmet T-cell ifiltratio of tumors iclude vaccies targetig established ocogeic drivers such as the geomic amplificatio of HER2. We costructed a vaccie based o a ovel alphaviral vector e...
Article
Full-text available
Despite of an extensive statistical literature showing that discretizing continuous variables results in substantial loss of information, categorization of continuous variables has been a common practice in clinical research and in cancer dose finding (phase I) clinical trials. The objective of this study is to quantify the loss of information incu...
Data
R Code. R Code used for the simulations. (ZIP)
Data
Data. Data obtained from the simulations. (ZIP)
Article
Background Admission medication history (AMH) errors frequently cause medication order errors and patient harm. Objective To quantify AMH error reduction achieved when pharmacy staff obtain AMHs before admission medication orders (AMO) are placed. Methods This was a three-arm randomised controlled trial of 306 inpatients. In one intervention arm,...
Article
We present a Bayesian adaptive design for dose finding in cancer phase I clinical trials. The goal is to estimate the maximum tolerated dose (MTD) after possible modification of the dose range during the trial. Parametric models are used to describe the relationship between the dose and the probability of dose limiting toxicity (DLT). We investigat...
Article
Although there is an extensive statistical literature showing the disadvantages of discretizing continuous variables, categorization is a common practice in clinical research which results in substantial loss of information. A large collection of methods in cancer phase I clinical trial design establishes dose of a new agent as a discrete variable....
Article
Objective: To identify the optimal clinical criteria to diagnose Hirschsprung-associated enterocolitis (HAEC) in children with Hirschsprung disease (HSCR). Background: HAEC is the most common life-threatening complication in HSCR patients, yet the diagnostic criteria for HAEC remain unclear. The consensus-based HAEC scoring system was not valida...
Conference Paper
5031 Background: The presence of VM in metastatic, castration-resistant prostate cancer (mCRPC) predicts poor survival. Cabozantinib (cabo) is a multi-kinase inhibitor that has clinical activity that did not improve survival in an unselected mCRPC population. Subgroup analyses suggested that the benefit may exist for patients (pts) with mCRPC-VM. T...
Article
We present a cancer phase I clinical trial design of a combination of two drugs with the goal of estimating the maximum tolerated dose curve in the two-dimensional Cartesian plane. A parametric model is used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity. The model is re-parameterized...
Article
TPS487 Background: Targeted inhibition of PARP1/2 is one way to further exploit the well-known synergy between gemcitabine (G) and radiotherapy (RT) in locally advanced pancreatic cancer (LAPC). PARP1/2 inhibitors, such as veliparib (V), have shown excellent anti-tumor activity when used with other cytotoxic therapies. This synergy may be further e...
Conference Paper
208 Background: Cabozantinib is a multi-targeted tyrosine kinase inhibitor (TKI) that has recognized clinical activity in mCRPC. While phase 3 studies did not show a significant improvement in overall survival (OS), patients with VM had improved OS compared to those with only osseous metastases in subgroup analysis. Our group has also identified a...
Article
Full-text available
We describe a Bayesian adaptive design for early phase cancer trials of a combination of three agents. This is an extension of an earlier work by the authors by allowing all three agents to vary during the trial and by assigning different drug combinations to cohorts of three patients. The primary objective is to estimate the Maximum Tolerated Dose...
Article
Full-text available
Aims: The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocard...
Article
Full-text available
The standard 3 + 3 or " modified Fibonacci " up-and-down (MF-UD) method of dose escalation is by far the most used design in dose-finding cancer trials. However, MF-UD has always shown inferior performance when compared with its competitors regarding number of patients treated at optimal doses. A consequence of using less effective designs is that...
Article
Hybrid positron emission tomography (PET) myocardial perfusion imaging (MPI) with computed tomography (CT) allows the incorporation of coronary artery calcium (CAC) into the clinical protocol. We aimed to determine whether the combined analysis of MPI and CAC could improve the diagnostic accuracy of PET MPI in detection of obstructive coronary arte...
Article
Full-text available
Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult pa...
Conference Paper
Background: Hematopoietic stem cell transplantation (HCT) is used with curative intent for the treatment of many blood cancers and chronic blood disorders. Patients undergoing HCT are known to experience increased fatigue, reduced physical activity, diminished functioning, and poorer quality of life after HCT. Additionally, these survivors have hig...
Article
Full-text available
Purpose: Altered PI3K/mTOR pathway is implicated in lung cancer but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non-small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. Experimental Design: We enrolled 33 patie...
Chapter
Futility designs have been proposed and used by constructing classical (non-Bayesian) hypothesis tests such that the decision of therapeutic interest is to accept the null hypothesis. A consequence is that the probability of accepting (failing to reject) the null when the null is false is unknown. Reversal of the conventional null and alternative h...
Article
Background: Patients with inflammatory bowel disease-unclassified (IBDU) undergoing ileal pouch-anal anastomosis (IPAA) are at the risk of developing Crohn's disease (CD) after surgical procedure. In these patients, a clinically centered set of preoperative risk factors has not been prospectively defined. We report a single-center analysis of clin...
Article
Background: Coronary endothelial dysfunction is typically assessed by invasive coronary reactivity testing (CRT) to measure coronary blood flow ([[Unable to Display Character: ∆]]CBF) and diameter responses to acetylcholine (Ach). We evaluated if cold pressor testing (CPT) during noninvasive cardiac magnetic resonance imaging (CMRI) measurement of...
Article
We present a Bayesian adaptive design for dose finding of a combination of two drugs in cancer phase I clinical trials. The goal is to estimate the maximum tolerated dose (MTD) as a curve in the two-dimensional Cartesian plane. We use a logistic model to describe the relationship between the doses of the two agents and the probability of dose limit...
Article
Aim: Cabozantinib (XL184) is a potent multi-targeted tyrosine kinase inhibitor (TKI) that is under active investigation in several malignancies including prostate cancer (PC). The mechanism of action in PC has not been well characterized at this time. While considerable attention has been given to the impact of this agent on Tc-bone scans, less is...
Article
Full-text available
Tumor-stromal interaction is a dynamic process that promotes tumor growth and metastasis via cell-cell interaction and extracellular vesicles. Recent studies demonstrate that stromal fibroblast-derived molecular signatures can be used to predict disease progression and drug resistance. To identify the epigenetic role of stromal noncoding RNAs in tu...
Article
Full-text available
Purpose: miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progres...
Article
Background: Cardiac magnetic resonance imaging (CMRI) quantitative myocardial perfusion reserve index (MPRI) has been shown to predict prognosis in women with persistent chest pain and no obstructive coronary artery disease. A prior study of healthy men revealed that regadenoson produces higher MPRI than adenosine but differences disappear after ad...
Article
Full-text available
Prostate cancer (PCa) metastasis to bone is lethal and there is no adequate animal model to study the mechanisms underlying the metastatic process. Here we report that receptor activator of NF-κB ligand (RANKL) expressed by PCa cells consistently induced colonization or metastasis to bone in animal models. RANK-mediated signaling established a prem...
Article
Determine predictive factors for TRansferring Inpatient rehabilitation facility (IRF) cancer Patients Back to Acute Care (TRIPBAC). Retrospective chart review of patients with cancer admitted to the IRF because of a functional impairment that developed as a direct consequence of their cancer or its treatment from 2009 - 2010. IRF of a community-bas...