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

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.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.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.Medulloblastoma is a relatively common primary tumor of the central nervous system (CNS) in the pediatric population, representing about 20% of brain tumors in this group [1]. The mainstays of treatment include maximal surgical resection followed by chemotherapy and radiation to the entire craniospinal axis (brain and spine), also known as craniospinal irradiation (CSI) [2]. Radiotherapists treat the entire craniospinal axis because the tumor cells have direct axis to the subarachnoid space, and, hence, the cerebrospinal fluid (CSF), which can provide a route for metastatic spread throughout the craniospinal axis. Early clinical studies indicated the importance of full CSI as opposed to treatment of smaller, gross-tumor-directed volumes [3]. Various clinical trials have been performed or are underway to study reduction of the radiation dose and attendant complications of CSI, possibly by way of intensifying chemotherapy. Nonetheless, CSI has retained its role as a critical component in the multimodality management of medulloblastoma [4,5].Other primary and metasta