paediatrics Brussels 17

Childs Nerv Syst

als were 69% and 81%, respectively The 7-year local control rate was 87%. A subset of patients treated with immediate postoperative radiation therapy were found to have even high rates of local control (89%), event-free (77%), and overall survival (85%) when estimated at 7 years. Extent of resection and tumor grade remain important prognostic factors. Among the patients with differentiated ependymoma treated with GTR and 59.4 Gy, there were very few failures. These data define potential groups for treatment intensification or reduction. More than a decade later, sufficient experience has been gained to confirm the promise of conformal radiation therapy in pediatric CNS tumors and document improve- ments in disease control and preservation of functional outcomes in childhood ependymoma. In this report, we will summarize the data available from the treatment and follow-up of children irradiated using conformal radiation therapy including information on side effects. Conformal radiation therapy is defined as forward planned three-dimensional conformal radiation therapy or inverse planned intensity-modulated radiation therapy (IMRT) using photons. The goal of treatment is to achieve conformity of the prescription dose to the targeted volume and to spare normal tissues including the noninvolved brain, brainstem, spinal cord, optic chiasm, hypothalamus, and functional subunits of the cerebral hemispheres or cerebellum. The nomenclature used to define target vol- umes for conformal radiation therapy were first issued by the International Commission on Radiation Units and Measurements (ICRU) in 1993 and first used in a clinical trial for ependymoma beginning in 1997 [ 21 , 22 ]. The ICRU defines the gross tumor volume (GTV) as the imaging visible residual tumor or volume of greatest tumor burden. The clinical target volume (CTV) is defined by a margin surrounding the GTV that includes microscopic tumor extension and depends on the tumor. The planning target volume (PTV) is an additional margin surrounding the CTV that is meant to account for variability in patient positioning. To date, these definitions have been used with one modification: The GTV has been defined to include residual tumor and/or the tumor bed. This modification fits with the concept of greatest tumor burden. Recent trials have prescribed CTV margins of 10 mm and PTV margins of 3 – 5 mm (Fig. 1 ). Conformal radiation therapy requires specialized hard- ware and software. Both are now widely available. The first step in conformal therapy planning is computed tomogra- phy (CT) imaging in the treatment position. CT is the fundamental data set for three-dimensional treatment Materials and methods

lung tumors could be safely escalated to increase tumor control. Most convincing was the noticeable reduction in acute side effects leading radiation oncologists to consider the application of the same techniques in pediatric CNS tumors. The advent of conformal radiation therapy set the stage for a renewed look at the role of radiation therapy in the treatment of children with ependymoma. A prospective phase II trial (RT-1) was conducted at St. Jude Children ’ s Research Hospital between 1997 and 2003. The primary goals were to objectively document the side effects of radiation therapy and to demonstrate that tumor control with a 10-mm clinical target volume margin was equivalent to conventional radiation therapy. Eighty-eight patients with ependymoma were enrolled during a 5-year period and most were under the age of 3 years at the time of irradiation. For the first time, radiation therapy was a component of frontline management in a clinical trial for children under the age of 3 years. The rate of gross-total resection (GTR) exceeded 85% as patients were systemat- ically referred for second surgery prior to radiation therapy to minimize the amount of residual tumor. Through this process, the feasibility and safety of second surgery were demonstrated. The reported 3-year progression-free survival was 75% and the 3-year cumulative incidence of local failure was 15% [ 17 ]. These results were attributed to the high rate of gross-total resection, newer radiation planning and delivery methods, the relatively high dose tolerances for the cervical spinal cord and optic chiasm, and a cumulative planning target volume dose of 59.4 Gy with 100% coverage. As presented in the same report, the side effects of radiation therapy were found to be limited in this vulnerable patient population. Baseline and longitudinal testing using the prospective battery of neurologic, endo- crine, and cognitive testing continue to demonstrate that most long-term survivors function within the range of normal. Radiation dosimetry was found to correlate with functional outcomes supporting the goal of target volume reduction in this vulnerable group of patients [ 18 ]. The results of this study were widely accepted as a major advance, especially for very young children. As these results were unfolding, investigators in the Children ’ s Oncology Group (COG) supported the development and implementation of the ACNS0121 protocol which was based on the concepts of conformal therapy developed at St. Jude Children ’ s Research Hospital. The COG protocol was activated in August 2003, widely accepted, and reached its goal of 350 eligible patients in 4 years [ 19 ]. In early 2009, an update in the series of patients treated at St. Jude Children ’ s Research Hospital was published that included 153 patients [ 20 ]. With a median follow-up of 62 months (range 3 – 112 months) from the initiation of radiation therapy, the 7-year event-free and overall surviv-