Location: Cleveland Clinic Main Campus
My goal is to develop a model-based dose decision support tool that will suggest doses that minimize the sum of the risks of death by disease and by drug for chronic myeloid leukemia (CML) patients. Best doses will drive CML loads down rapidly at high loads posing high progression risks and as loads lower to ones with low progression risks, they will drive loads down more slowly to focus instead on lowering toxicity risks.
Tomas Radivoyevitch, PhD, is Associate Staff in the Department of Quantitative Health Sciences. His focus is on developing response-based dose reduction algorithms for patients with chronic myeloid leukemia.
Associate Staff - Cleveland Clinic
Assitant Professor - Case Western Reserve Univeristy
Cleveland, OH USA
Visiting Research Mathematician - University of California
Berkeley, CA USA
PhD - Medical University of South Carolina
Charleston, SC USA
Coming to cancer research from process control engineering, I decided to focus on hematologic malignancies because, given the accessibility of blood, cancer state feedback should be richest for such cancers. I then decided to focus on chronic myeloid leukemia (CML) because it is simple/well understood. My goal is to develop patient-specific mathematical models of CML that can be used to adjust doses to minimize total risks of death by drug and by disease.
I program in R, a high-level scripting language and statistical computing environment.
View publications for Tomas Radivoyevitch, PhD
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Klippenstein, S. J. and Radivoyevitch, T., A theoretical study of the dissociation of NO2. J Chem Phys 99, 3644-3653 (1993).
Radivoyevitch, T. and Cedervall, B., Mathematical analysis of DNA fragment distribution models used with pulsed-field gel electrophoresis for DNA double-strand break calculations. Electrophoresis 17, 1087-1093 (1996).
Radivoyevitch, T., Hoel, D. G., Hahnfeldt, P. J., Rydberg, B. and Sachs, R. K., Recent data obtained by pulsed-field gel electrophoresis suggest two types of double-strand breaks. Radiat Res 149, 52-58 (1998).
Radivoyevitch, T., Hoel, D. G., Chen, A. M. and Sachs, R. K., Misrejoining of double-strand breaks after X irradiation: relating moderate to very high doses by a Markov model. Radiat Res 149, 59-67 (1998).
Radivoyevitch, T., Hoel, D. G., Hahnfeldt, P. and Sachs, R. K., Size distributions of misrejoining DNA fragments in irradiated cells. Math Biosci 149, 107-136 (1998).
Radivoyevitch, T., Ramsey, M. J. and Tucker, J. D., Estimation of the target stem-cell population size in chronic myeloid leukemogenesis. Radiat Environ Biophys 38, 201-206 (1999).
Radivoyevitch, T. and Hoel, D. G., Modeling the low-LET dose-response of BCR-ABL formation: predicting stem cell numbers from A-bomb data. Math Biosci 162, 85-101 (1999).
Radivoyevitch, T. and Hoel, D. G., Biologically-based risk estimation for radiation-induced chronic myeloid leukemia. Radiat Environ Biophys 39, 153-159 (2000)
Radivoyevitch, T., Time course solutions of the Sax-Markov binary eurejoining/misrejoining model of DNA double-strand breaks. Radiat Environ Biophys 39, 265-273 (2000).
Voit, E. O. and Radivoyevitch, T., Biochemical systems analysis of genome-wide expression data. Bioinformatics 16, 1023-1037 (2000)
Radivoyevitch, T., The death-mutation model of carcinogenesis. Mathematical and Computer Modeling 33, 1219-1226 (2001).
Radivoyevitch, T., Kozubek, S. and Sachs, R. K., Biologically based risk estimation for radiation-induced CML. Inferences from BCR and ABL geometric distributions. Radiat Environ Biophys 40, 1-9 (2001).
Radivoyevitch, T., Sphingoid base metabolism in yeast: Mapping gene expression patterns into qualitative metabolite time course predictions. Comparative & Functional Genomics 2, 289-294 (2001).
Radivoyevitch, T., Kozubek, S. and Sachs, R. K., The risk of chronic myeloid leukemia: can the dose-response curve be U- shaped? Radiat Res 157, 106-109 (2002).
Radivoyevitch, T., A two-way interface between limited Systems Biology Markup Language and R. BMC Bioinformatics 5, 190 (2004).
Radivoyevitch, T., Taverna, P., Schupp, J. E. and Kinsella, T. J., The Linear-Quadratic Log-Survival Radiation Dose Response Model: Confidence Ellipses, Drug-Drug Interactions and Brachytherapeutic Gains. Medical Hypotheses and Research 1, 23-28 (2004).
Radivoyevitch, T., Folate system correlations in DNA microarray data. BMC Cancer 5, 95 (2005).
Radivoyevitch, T., Loparo, K.A., Jackson, R.C. and Sedwick, W.D., On systems and control approaches to therapeutic gain. BMC Cancer 6, 104 (2006).
Radivoyevitch, T., Equilibrium model selection: dTTP induced R1 dimerization. BMC Syst Biol 2, 15 (2008)
Radivoyevitch, T., Mass action models versus the Hill model: An analysis of tetrameric human thymidine kinase 1 positive cooperativity. Biol Direct 4, 49 (2009).
Radivoyevitch, T., Automated mass action model space generation and analysis methods for two-reactant combinatorially complex equilibriums: An analysis of ATP-induced ribonucleotide reductase R1 hexamerization data. Biol Direct 4, 50 (2009).
Radivoyevitch, T., How to use the computing environment R to analyze ATP-induced ribonucleotide reductase R1 hexamerization data. Nucleosides Nucleotides Nucleic Acids 29, 427-432 (2010).
Radivoyevitch, T., Munch-Petersen, B., Wang, L. and Eriksson, S., A mathematical model of human thymidine kinase 2 activity. Nucleosides Nucleotides Nucleic Acids 30, 203-209 (2011).
Radivoyevitch, T., Saunthararajah, Y., Pink, J., Ferris, G., Lent, I., Jackson, M., Junk, D. and Kunos, C. A., dNTP Supply Gene Expression Patterns after P53 Loss. Cancers (Basel) 4, 1212-1224 (2012).
Radivoyevitch, T., Hlatky, L., Landaw, J. and Sachs, R. K., Quantitative modeling of chronic myeloid leukemia: insights from radiobiology. Blood 119, 4363-4371 (2012).
Radivoyevitch T, Saunthararajah Y. Sex Difference in Myelodysplastic Syndrome Survival and Balance in Randomized Clinical Trials. J Clin Oncol. 32, 60-1 (2014).
Radivoyevitch, T., Jankovic, G. M., Tiu, R. V., Saunthararajah, Y., Jackson, R. C., Hlatky, L. R., Gale, R. P. and Sachs, R. K. Sex differences in the incidence of chronic myeloid leukemia. Radiat Environ Biophys. 53, 55-63 (2014)
Gale R. P., Hlatky L. R., Sachs R. K., and Radivoyevitch T. Why is there so much therapy-related AML and MDS and so little therapy-related CML? Leukemia Research 38, 1162-4 (2014).
Radivoyevitch, T., Li, H., and Sachs, R. K. Etiology and Treatment of Hematological Neoplasms: Stochastic Mathematical Models. In A Systems Biology Approach to Blood (S. J. Corey, M. Kimmel and J. N. Leonard, Editors), Springer. Adv Exp Med Biol 844, 317-46 (2014).
Radivoyevitch, T., Siranart, N., Hlatky, L., Sachs, R. K. Stochastic process pharmacodynamics: dose timing in neonatal gentamicin therapy as an example. AAPSJ 17, 447-56 (2015).
Radivoyevitch, T., Sachs, R. K., Gale, R. P., Molenaar, R. J., Brenner, D. J., Hill, B. T., Kalaycio, M. E., Carraway, H. E., Mukherjee, S., Sekeres, M. A. and Maciejewski, J. P. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation. Leukemia 30, 285-94 (2016).
Radivoyevitch, T., Sachs, R. K., Gale, R. P., Smith, M. R. and Hill, B. T. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia. Leuk Res 43, 9-12 (2016).
Radivoyevitch, T., Jorgensen, T. N., Lindner, D. J., Maciejewski, J. P., Miyazaki, Y. and Gale, R. P. Chronic myeloid leukemia: Two mysteries. Leukemia Research 79, 3-5 (2019).
Radivoyevitch, T., Weaver, D., Hobbs, B., Maciejewski, J. P., Hehlmann, R., Jiang, Q., Hochhaus, A. and Gale, R.P. Do persons with chronic myeloid leukaemia have normal or near normal survival? Leukemia 34, 333-335 (2020).
Radivoyevitch, T. Parameter perturbations in a post-treatment chronic myeloid leukemia model capture the essence of pre-diagnosis A-bomb survivor mysteries. Radiat Environ Biophys 60, 41-47 (2021).