SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM)

Yu, V; Nguyen, D; Kupelian, P; Kaprealian, T; Selch, M; Low, D; Pajonk, F; Sheng, K

doi:10.1118/1.4889709

Title: SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM)

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Abstract

Purpose: To explore the aggressive recurrence and radioresistence of GBM with a dual compartment tumor survival mathematical model based on intrinsic tumor heterogeneity, cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The repopulation and differentiation responses to radiotherapy of a solid tumor were simulated using an Ordinary Differential Equation (ODE). To obtain the tumor radiobiological parameters, we assumed that a tumor consists of two subpopulations, each with its distinctive linear quadratic parameters. The dual compartment cell survival model was constructed as SF(D)=F × exp(-α{sub 1} D-β{sub 1}D{sup 2}) + (1-F) × exp(-α{sub 2}D-β{sub 2}D{sup 2}) for a single fraction of treatment, with F as the fraction of CSC, and α and β describing the radiological properties of each population. Robust least square fitting was performed on clonogenic survival data from one GBM (U373MG) and one NSCLC (H460) cell line. The fit parameters were then used in the ODE model to predict treatment outcome of various treatment schemes. Results: The fit parameters from GBM cell survival data were (F, α{sub 1}, β{sub 1}, α{sub 2}, β{sub 2})=(0.0396, 0.0801, 0.0006, 0.1363, 0.0279), exhibiting two populations with distinctive radiological properties, CSC more radioresistant than DCC. The GBM cell line exhibited significantlymore »« less

Authors:

Yu, V; Nguyen, D; Kupelian, P; Kaprealian, T; Selch, M; Low, D; Pajonk, F; Sheng, K ^[1]

UCLA, Los Angeles, CA (United States)

Publication Date:: Sun Jun 15 00:00:00 EDT 2014

OSTI Identifier:: 22412434

Resource Type:: Journal Article

Journal Name:: Medical Physics

Additional Journal Information:: Journal Volume: 41; Journal Issue: 6; Other Information: (c) 2014 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0094-2405

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; FORECASTING; GLIOMAS; RADIATION DOSES; RADIOSENSITIVITY; RADIOTHERAPY; STEM CELLS

Citation Formats


                    Yu, V, Nguyen, D, Kupelian, P, Kaprealian, T, Selch, M, Low, D, Pajonk, F, and Sheng, K. SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM).  United States: N. p., 2014. 
        Web.  doi:10.1118/1.4889709.

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                    Yu, V, Nguyen, D, Kupelian, P, Kaprealian, T, Selch, M, Low, D, Pajonk, F, & Sheng, K. SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM).  United States.  https://doi.org/10.1118/1.4889709

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                    Yu, V, Nguyen, D, Kupelian, P, Kaprealian, T, Selch, M, Low, D, Pajonk, F, and Sheng, K. 2014.  
        "SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM)".  United States.  https://doi.org/10.1118/1.4889709.

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@article{osti_22412434,

  title        = {SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM)},

  author       = {Yu, V and Nguyen, D and Kupelian, P and Kaprealian, T and Selch, M and Low, D and Pajonk, F and Sheng, K},

  abstractNote = {Purpose: To explore the aggressive recurrence and radioresistence of GBM with a dual compartment tumor survival mathematical model based on intrinsic tumor heterogeneity, cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The repopulation and differentiation responses to radiotherapy of a solid tumor were simulated using an Ordinary Differential Equation (ODE). To obtain the tumor radiobiological parameters, we assumed that a tumor consists of two subpopulations, each with its distinctive linear quadratic parameters. The dual compartment cell survival model was constructed as SF(D)=F × exp(-α{sub 1} D-β{sub 1}D{sup 2}) + (1-F) × exp(-α{sub 2}D-β{sub 2}D{sup 2}) for a single fraction of treatment, with F as the fraction of CSC, and α and β describing the radiological properties of each population. Robust least square fitting was performed on clonogenic survival data from one GBM (U373MG) and one NSCLC (H460) cell line. The fit parameters were then used in the ODE model to predict treatment outcome of various treatment schemes. Results: The fit parameters from GBM cell survival data were (F, α{sub 1}, β{sub 1}, α{sub 2}, β{sub 2})=(0.0396, 0.0801, 0.0006, 0.1363, 0.0279), exhibiting two populations with distinctive radiological properties, CSC more radioresistant than DCC. The GBM cell line exhibited significantly poorer tumor control than its single compartment model prediction and NSCLC, which responded well to hypofrationation. The increased radioresistance was due to rapid regrowth of the DCC compartment triggered by its depletion while maintaining a viable CSC population. The rapid regrowth can be reduced by treating dose fractions ≤ 2 Gy with a prolonged treatment period. Conclusion: The interaction between a radioresistant CSC compartment and DCC compartment can explain the poor clinical outcome of GBM after radiotherapy despite dose escalation and hypofractionation attempts. Lower dose fractions result in better treatment outcome but still eventually recurs. Dose escalation beyond 100 Gy and/or differentiation therapy will be vital in achieving GBM tumor control.},

  doi          = {10.1118/1.4889709},

  url          = {https://www.osti.gov/biblio/22412434},
  journal      = {Medical Physics},

  issn         = {0094-2405},

  number       = 6,

  volume       = 41,

  place        = {United States},

  year         = {Sun Jun 15 00:00:00 EDT 2014},

  month        = {Sun Jun 15 00:00:00 EDT 2014}

}

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