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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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Scenario II. A break lasting three weeks is instituted. a) Treatment results when flow is not allowed. The number of cells in the spine compartment never reaches an appreciable level and the patient is cured. b) Tumor growth when flow is allowed between the brain and spine. The patient is not cured since the spine compartment is not sterilized.
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Figure 4: Scenario II. A break lasting three weeks is instituted. a) Treatment results when flow is not allowed. The number of cells in the spine compartment never reaches an appreciable level and the patient is cured. b) Tumor growth when flow is allowed between the brain and spine. The patient is not cured since the spine compartment is not sterilized.

Mentions: In this scenario II (Figure 4), results following the introduction of a 3-week break in the spine portion of the treatment are described. As described above, such breaks may be necessitated when the acute reactions of the spine portion of CSI become life-threatening. The deleterious impact of treatment delay on outcomes in medulloblastoma has been documented in several retrospective series [18-20]. The kinetic model recapitulates this finding. In Figure 4a (with Qf = 25 ml/hr), the introduction of the break prevents sterilization of the spine phases, which were nearing sterilization just prior to the break. Enough cells remain to eventually repopulate all phases in the model. In a version of the model not allowing for flow (Qf = 0), shown in Figure 4b, the break never becomes an issue for cure because the spine is never seeded with cells from the brain. The brain compartment is easily sterilized with 54 Gy.


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)

Scenario II. A break lasting three weeks is instituted. a) Treatment results when flow is not allowed. The number of cells in the spine compartment never reaches an appreciable level and the patient is cured. b) Tumor growth when flow is allowed between the brain and spine. The patient is not cured since the spine compartment is not sterilized.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Scenario II. A break lasting three weeks is instituted. a) Treatment results when flow is not allowed. The number of cells in the spine compartment never reaches an appreciable level and the patient is cured. b) Tumor growth when flow is allowed between the brain and spine. The patient is not cured since the spine compartment is not sterilized.
Mentions: In this scenario II (Figure 4), results following the introduction of a 3-week break in the spine portion of the treatment are described. As described above, such breaks may be necessitated when the acute reactions of the spine portion of CSI become life-threatening. The deleterious impact of treatment delay on outcomes in medulloblastoma has been documented in several retrospective series [18-20]. The kinetic model recapitulates this finding. In Figure 4a (with Qf = 25 ml/hr), the introduction of the break prevents sterilization of the spine phases, which were nearing sterilization just prior to the break. Enough cells remain to eventually repopulate all phases in the model. In a version of the model not allowing for flow (Qf = 0), shown in Figure 4b, the break never becomes an issue for cure because the spine is never seeded with cells from the brain. The brain compartment is easily sterilized with 54 Gy.

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