The first model included measurements during treatment including before RT and at 2 and 24 h, and Weeks 16 of RT

The first model included measurements during treatment including before RT and at 2 and 24 h, and Weeks 16 of RT. of 0.10389/wk (p= 0.0068). The rate of decline was greater (p= 0.028) for patients with an infratentorial tumor location. The decline in IL-8 after RT was significant when stratified by infratentorial tumor location (p= 0.0345) and more than one surgical procedure (p= 0.0272). During RT, the decline in log VEGF was significant when stratified by the presence of a ventriculoperitoneal shunt. After RT, the log VEGF declined significantly at a rate of 0.06207/mo. The decline was significant for males (p= 0.0222), supratentorial tumors (p= 0.0158), one surgical procedure (p= Akt1 0.0222), no ventriculoperitoneal shunt (p= 0.0005), and the absence of treatment failure (p= 0.0028). == Conclusion == The pro-inflammatory cytokine IL-8 declined significantly during RT and the decline differed according to tumor location. The angiogenesis factor VEGF declined significantly during the 12 months after RT. The decline was greater in males, those without a ventriculoperitoneal shunt, and in those with favorable disease factors, including one surgical procedure, supratentorial tumor location, and tumor control. Keywords:Radiotherapy, Pediatrics, Ependymoma, Cytokines, Central nervous system tumors == INTRODUCTION == Ependymoma describes a diverse group of central nervous system tumors that can develop at any age (1). Successful therapy requires aggressive surgical intervention, accurate evaluation to determine the neuraxis extent of the tumor, and radiotherapy (RT) administered using methods that minimize the risk of side effects (2). The clinical and laboratory research performed during the past decade has resulted in important discoveries related to the biology of this tumor and the clinical and treatment factors that are prognostic for disease control (3). Future advances in the treatment of ependymoma, similar to other brain tumors, will require objective clinical and molecular information to identify patients at best risk of failure after optimal treatment, patients with a good prognosis who would be eligible for a reduction in adjuvant therapy, and markers for side effects so that early intervention could be provided. Ependymoma most often affects the very young, and because the requirement for RT has been viewed with trepidation because of the risk of side effects, we focused on studying the side effects of RT in the context of modern treatment that includes aggressive medical procedures, with the goal of gross total resection, and postoperative RT. Cytokines and growth factors have been identified as predictors or correlates of radiation effects in a number of systems; however, limited data are available to characterize the induction of these markers in the central nervous system (4,5). We have shown a time-dependent change in the central nervous system tissue levels of tumor necrosis factor-in mice. A significant Angiotensin (1-7) elevation was observed for this cytokine within 2 h of a single dose of RT (6). This elevation preceded an inflammatory response, determined by a leukocyteendothelial cell conversation and an increase in intercellular adhesion module-1 mRNA and protein levels, which we have shown to peak in the cerebral vessels of the rat during the first 2448 h after RT (6,7). Because vascular permeability is also increased in a similar fashion after RT, we postulated that this cytokines induced by the act of RT attract inflammatory cells to the extravascular compartment where tissue destruction is initiated that could eventually be clinically significant. The time course and clinical significance of cytokines, peptide growth factors, and other biologic markers of central nervous system injury after RT is usually unknown; we chose to study these response markers in children with ependymoma. In searching for clinical biomarkers that would monitor the normal tissue and tumor response to postoperative RT, we prospectively measured the serum levels of specific growth factors and cytokines during and after RT in children with localized ependymoma. == METHODS AND MATERIALS == == Patients == The study included 30 patients with intracranial ependymoma prospectively treated with focal RT between June 7, 2001 and February 5, 2003. All patients underwent conformal or intensity-modulated RT using a 1-cm clinical target volume margin. Of the 30 patients, 59.4 Gy was prescribed in 24 and 54 Gy in 6. The latter prescription was decided from the protocol-specified dose for patients Angiotensin (1-7) with the characteristics of gross total resection and age <18 months at RT. The main results of the analysis detailed in this report concern interleukin (IL)-8 and vascular endothelial growth factor (VEGF). Because the 27 patients contributing to the IL-8 and the 27 patients contributing to the VEGF measurements were not identical, we have provided the patient characteristics Angiotensin (1-7) for the combined and individual groups inTable 1. == Table 1. == Patient characteristics Abbreviations:IL-8 = interleulin-8; VEGF = vascular endothelial growth factor; RT = radiotherapy; SD = standard deviation; AEP = anaplastic ependymoma; ED =.