In the newly diagnosed patient, careful evaluation to fully determine the extent of disease must precede the treatment of ependymoma. Surgery should be performed in an attempt at maximal tumor reduction; children have improved progression-free survival if there is minimal residual disease present after surgery.[1,2] Postoperatively, magnetic resonance imaging (MRI) should be performed to determine the extent of resection. If not performed preoperatively, MRI of the entire neuroaxis should be obtained to evaluate for disease dissemination. Even myxopapillary ependymomas, considered to be a somewhat benign histologic subtype of ependymoma, have a relatively high incidence of central nervous system (CNS) tumor dissemination at diagnosis and at followup, thus, underscoring the need for imaging of the complete cranial spinal axis at the time of diagnosis and during follow-up.[3] Patients with residual tumor or disseminated disease should be considered at high risk for relapse and should be treated on protocols specifically designed for them. Those with no evidence of residual tumor still have an approximate 20% to 40% relapse risk in spite of postoperative radiation therapy.

Postsurgical Treatment Options

Standard treatment options

• NO RESIDUAL DISEASE; NO DISSEMINATED DISEASE:

  The traditional postsurgical treatment for these patients has been radiation therapy consisting of 54 to 55.8 Gy to the tumor bed for children aged 3 years and older and is under evaluation for children younger than 3 years. It is not necessary to treat the entire CNS (whole brain and spine) because these tumors usually recur at the local site.[2,4] When possible, patients should be treated in a center experienced with this therapy. There is no evidence that adjuvant chemotherapy improves the outcome for patients with totally resected, nondisseminated ependymoma. The 3-year progression-free survival rate in 74 patients aged between 1 and 21 years treated with radiation therapy following surgery was 77.6% ± 5.8%.[5] Limited experience with surgery alone for completely resected supratentorial nonanaplastic tumors suggests that, in select cases, this may be an option.[6]

• RESIDUAL DISEASE; NO DISSEMINATED DISEASE:

  Second-look surgery should be considered because patients who have complete resections have better disease control. The traditional postsurgical treatment for children aged 3 years and older has been radiation therapy consisting of 54 to 55.8 Gy to the tumor bed. It is not necessary to treat the entire CNS (whole brain and spine) because these tumors usually recur at the local site. In subtotally resected patients, treatment with radiation therapy results in 3-year to 5-year progression-free survival in 30% to 50% of patients.[5,7] There is no evidence that adjuvant chemotherapy, including high-dose chemotherapy with stem cell rescue, is of any benefit.[8]

• CNS DISSEMINATED DISEASE:

  In children with disseminated disease, long-term survivors have been reported and aggressive therapy is warranted. Regardless of degree of surgical resection, these patients require radiation therapy to the entire CNS (whole brain and spine) along with boosts to local disease and bulk areas of disseminated disease. The traditional local postsurgical radiation doses in these patients have been 54 to 55.8 Gy. Doses of approximately 36 Gy to the entire neuraxis (i.e., the whole brain and spine) should also be administered, but may be modulated depending on the age of the patient. Boosts between 41.4 Gy and 50.4 Gy to bulk areas of spinal disease should be administered, with doses depending on the age of the patient and the location of the tumor. When possible, patients should be treated in a center experienced with this therapy. Trials are ongoing to evaluate the possible role of radiation therapy and chemotherapy in these patients.

• MANAGEMENT OF CHILDREN YOUNGER THAN 3 YEARS:

  Because of the known effects of radiation on growth and neurocognitive development, radiation therapy immediately after surgery in children younger than 3 years has traditionally been limited, with attempts to delay its administration through the use of chemotherapy.[9,10,11,12] When analyzing neurologic outcome following treatment of young children with ependymoma, it is important to consider that not all long-term deficits can be ascribed to radiation therapy, as deficits may be present in young children before therapy is begun.[5] For example, the presence of hydrocephalus at diagnosis is associated with lower intelligence quotient as measured following surgical resection and prior to administration of radiation therapy.[13]

  Chemotherapy is able to induce objective responses in some children younger than 3 years with newly diagnosed ependymoma,[9,10,11] though not all chemotherapy regimens induce objective responses.[12] Most young children with ependymoma treated with chemotherapy alone following their initial surgical resection will eventually develop progressive disease, though a minority of children may achieve long-term survival with chemotherapy alone.[11,12,14] The need and timing of radiation therapy for children who have successfully completed chemotherapy and have no residual disease is still to be determined. Current approaches to treating young children with ependymoma do not generally employ chemotherapy to delay use of radiation therapy.

  Conformal radiation therapy is an alternative approach for minimizing radiation-induced neurologic damage in young children with ependymoma. The initial experience with this approach suggests that children with ependymoma younger than 3 years have neurologic deficits at diagnosis that improve with time following conformal radiation treatment.[5] The current Children's Oncology Group (COG) protocol for children with ependymoma includes young children aged 12 to 36 months and is evaluating whether conformal radiation therapy can minimize neurologic late effects while producing long-term survival.