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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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The phases and compartments of the model. The rate constants shown govern the flow of tumor between the phases.
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Figure 2: The phases and compartments of the model. The rate constants shown govern the flow of tumor between the phases.

Mentions: The craniospinal axis is considered as having two tissue compartments, brain (b) and spine (s), with two phases, solid tumor (t) and cerebrospinal fluid (f), within each compartment (Figure 2). In the model the brain is not subdivided into supratentorial and posterior fossa (where medulloblastomas arise) compartments but rather as a single compartment. Recognizing that CSF flow is temporally and spatially heterogeneous [12], we assume that each fluid phase is well-mixed, as a crude approximation. Between the two compartments, cell transfer is governed by the volumetric flow rate, Qf, and the cell concentration in the fluid phases, i.e., the number of cells in the fluid phase divided by the volume of that phase. This is a reasonable assumption since the CSF flows relatively freely between the brain and spine compartments. Within each tissue compartment, transfer of cells between the phases is determined by the rate of adhesion of cells from the fluid phase onto the solid phase and by the rate of shedding of cells from the solid phase into the fluid phase. We assume that adhesion and shedding are described by the product of cell number and the rate constants kadh and kshed, respectively. However, not all of the cells shed into the fluid phase will be viable, and adhesion will account for only a portion of the cells cleared from the CSF. This is accounted for in the model by incorporating modulating efficiency factors for transfer of viable cells from the CSF to solid tumor and from solid tumor to CSF, γf and γt, respectively, which range in value from 0 to 1.


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)

The phases and compartments of the model. The rate constants shown govern the flow of tumor between the phases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: The phases and compartments of the model. The rate constants shown govern the flow of tumor between the phases.
Mentions: The craniospinal axis is considered as having two tissue compartments, brain (b) and spine (s), with two phases, solid tumor (t) and cerebrospinal fluid (f), within each compartment (Figure 2). In the model the brain is not subdivided into supratentorial and posterior fossa (where medulloblastomas arise) compartments but rather as a single compartment. Recognizing that CSF flow is temporally and spatially heterogeneous [12], we assume that each fluid phase is well-mixed, as a crude approximation. Between the two compartments, cell transfer is governed by the volumetric flow rate, Qf, and the cell concentration in the fluid phases, i.e., the number of cells in the fluid phase divided by the volume of that phase. This is a reasonable assumption since the CSF flows relatively freely between the brain and spine compartments. Within each tissue compartment, transfer of cells between the phases is determined by the rate of adhesion of cells from the fluid phase onto the solid phase and by the rate of shedding of cells from the solid phase into the fluid phase. We assume that adhesion and shedding are described by the product of cell number and the rate constants kadh and kshed, respectively. However, not all of the cells shed into the fluid phase will be viable, and adhesion will account for only a portion of the cells cleared from the CSF. This is accounted for in the model by incorporating modulating efficiency factors for transfer of viable cells from the CSF to solid tumor and from solid tumor to CSF, γf and γt, respectively, which range in value from 0 to 1.

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