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


CONCLUSIONS
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.
Meyer
Jeffrey J
JJ
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. meyer046@mc.duke.edu
Marks
Lawrence B
LB
Halperin
Edward C
EC
Kirkpatrick
John P
JP
D000465:Algorithms; D002528:Cerebellar Neoplasms / Q000532:radiotherapy*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D016371:Cranial Irradiation / Q000379:methods*; D006801:Humans; D007700:Kinetics; D008527:Medulloblastoma / Q000532:radiotherapy*; D015233:Models, Statistical; D008962:Models, Theoretical; D018787:Radiation Oncology / Q000379:methods*; D012306:Risk