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Kinetic modeling of tumor growth and dissemination in the craniospinal axis: implications for craniospinal irradiation.

Meyer JJ, Marks LB, Halperin EC, Kirkpatrick JP - Radiat Oncol (2006)

Bottom Line: The model accurately describes known clinical outcomes for patients with medulloblastoma.It can help guide treatment decisions for radiation oncologists treating patients with this disease.Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. meyer046@mc.duke.edu

ABSTRACT

Background: Medulloblastoma and other types of tumors that gain access to the cerebrospinal fluid can spread throughout the craniospinal axis. The purpose of this study was to devise a simple multi-compartment kinetic model using established tumor cell growth and treatment sensitivity parameters to model the complications of this spread as well as the impact of treatment with craniospinal radiotherapy.

Methods: A two-compartment mathematical model was constructed. Rate constants were derived from previously published work and the model used to predict outcomes for various clinical scenarios.

Results: The model is simple and with the use of known and estimated clinical parameters is consistent with known clinical outcomes. Treatment outcomes are critically dependent upon the duration of the treatment break and the radiosensitivity of the tumor. Cross-plot analyses serve as an estimate of likelihood of cure as a function of these and other factors.

Conclusion: The model accurately describes known clinical outcomes for patients with medulloblastoma. It can help guide treatment decisions for radiation oncologists treating patients with this disease. Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure.

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Related in: MedlinePlus

Cross-Plot Analyses. a) The interplay of kg,t and kg,f on treatment outcome, with and without growth of tumor cells in the fluid phase When kg,f is set to 0 (i.e., no growth of cells in the fluid phase), longer treatment breaks are allowed without threatening cure. b) The effect of efficiency factor γ is shown on treatment outcomes. Decreasing the efficiency of transfer of viable cells from one phase to the other (i.e., decreasing γt and/or γf) reduces the number of tumor cells, permitting a longer treatment break. c) The effect of independently varying γf and γt on treatment outcome is shown. High γt and low γf values versus the converse are associated with a higher risk of treatment failure for extended treatment breaks at all kg values. d) The effect of initial number of tumor cells in the brain parenchyma, Nb,t, and radiosensitivity, D0, on treatment outcome is shown. Failure is more likely the higher the value of Nb,t and D0.
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Figure 7: Cross-Plot Analyses. a) The interplay of kg,t and kg,f on treatment outcome, with and without growth of tumor cells in the fluid phase When kg,f is set to 0 (i.e., no growth of cells in the fluid phase), longer treatment breaks are allowed without threatening cure. b) The effect of efficiency factor γ is shown on treatment outcomes. Decreasing the efficiency of transfer of viable cells from one phase to the other (i.e., decreasing γt and/or γf) reduces the number of tumor cells, permitting a longer treatment break. c) The effect of independently varying γf and γt on treatment outcome is shown. High γt and low γf values versus the converse are associated with a higher risk of treatment failure for extended treatment breaks at all kg values. d) The effect of initial number of tumor cells in the brain parenchyma, Nb,t, and radiosensitivity, D0, on treatment outcome is shown. Failure is more likely the higher the value of Nb,t and D0.

Mentions: It is clear from the above scenarios, as well as from clinical experience, that multiple factors likely determine if a course of therapy is curative or not for medulloblastoma. To illustrate the sensitivity of cure, cross-plot analyses of treatment outcome as a function of several tumor and transport parameters was undertaken. In Figure 7, the impact of the values of kg,t, kg,f, γf, γt, D0 and the initial size of the brain tumor (Nb,t) on the maximum duration of treatment break duration is shown.


Kinetic modeling of tumor growth and dissemination in the craniospinal axis: implications for craniospinal irradiation.

Meyer JJ, Marks LB, Halperin EC, Kirkpatrick JP - Radiat Oncol (2006)

Cross-Plot Analyses. a) The interplay of kg,t and kg,f on treatment outcome, with and without growth of tumor cells in the fluid phase When kg,f is set to 0 (i.e., no growth of cells in the fluid phase), longer treatment breaks are allowed without threatening cure. b) The effect of efficiency factor γ is shown on treatment outcomes. Decreasing the efficiency of transfer of viable cells from one phase to the other (i.e., decreasing γt and/or γf) reduces the number of tumor cells, permitting a longer treatment break. c) The effect of independently varying γf and γt on treatment outcome is shown. High γt and low γf values versus the converse are associated with a higher risk of treatment failure for extended treatment breaks at all kg values. d) The effect of initial number of tumor cells in the brain parenchyma, Nb,t, and radiosensitivity, D0, on treatment outcome is shown. Failure is more likely the higher the value of Nb,t and D0.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1764894&req=5

Figure 7: Cross-Plot Analyses. a) The interplay of kg,t and kg,f on treatment outcome, with and without growth of tumor cells in the fluid phase When kg,f is set to 0 (i.e., no growth of cells in the fluid phase), longer treatment breaks are allowed without threatening cure. b) The effect of efficiency factor γ is shown on treatment outcomes. Decreasing the efficiency of transfer of viable cells from one phase to the other (i.e., decreasing γt and/or γf) reduces the number of tumor cells, permitting a longer treatment break. c) The effect of independently varying γf and γt on treatment outcome is shown. High γt and low γf values versus the converse are associated with a higher risk of treatment failure for extended treatment breaks at all kg values. d) The effect of initial number of tumor cells in the brain parenchyma, Nb,t, and radiosensitivity, D0, on treatment outcome is shown. Failure is more likely the higher the value of Nb,t and D0.
Mentions: It is clear from the above scenarios, as well as from clinical experience, that multiple factors likely determine if a course of therapy is curative or not for medulloblastoma. To illustrate the sensitivity of cure, cross-plot analyses of treatment outcome as a function of several tumor and transport parameters was undertaken. In Figure 7, the impact of the values of kg,t, kg,f, γf, γt, D0 and the initial size of the brain tumor (Nb,t) on the maximum duration of treatment break duration is shown.

Bottom Line: The model accurately describes known clinical outcomes for patients with medulloblastoma.It can help guide treatment decisions for radiation oncologists treating patients with this disease.Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. meyer046@mc.duke.edu

ABSTRACT

Background: Medulloblastoma and other types of tumors that gain access to the cerebrospinal fluid can spread throughout the craniospinal axis. The purpose of this study was to devise a simple multi-compartment kinetic model using established tumor cell growth and treatment sensitivity parameters to model the complications of this spread as well as the impact of treatment with craniospinal radiotherapy.

Methods: A two-compartment mathematical model was constructed. Rate constants were derived from previously published work and the model used to predict outcomes for various clinical scenarios.

Results: The model is simple and with the use of known and estimated clinical parameters is consistent with known clinical outcomes. Treatment outcomes are critically dependent upon the duration of the treatment break and the radiosensitivity of the tumor. Cross-plot analyses serve as an estimate of likelihood of cure as a function of these and other factors.

Conclusion: The model accurately describes known clinical outcomes for patients with medulloblastoma. It can help guide treatment decisions for radiation oncologists treating patients with this disease. Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure.

Show MeSH
Related in: MedlinePlus