SURVIVAL AND PROGNOSTIC FACTORS FOLLOWING RADIATION-THERAPY AND CHEMOTHERAPY FOR EPENDYMOMAS IN CHILDREN - A REPORT OF THE CHILDRENS CANCERGROUP

Object. Ependymomas in children continue to generate controversy regar ding their histological diagnosis and grading, optimal management, and possible prognostic factors. To increase our knowledge of these tumor s the authors addressed these issues in a cohort of children with pros pectively staged ependymomas treated with radiotherapy and chemotherap y. Methods. Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Canc er Group Protocol 921 from 1986 to 1992. Treatment following surgery a nd postoperative tumor staging (including brain computerized tomograph y or magnetic resonance [MR] imaging, spinal MR imaging or myelography , and cerebrospinal fluid cytological investigation) included craniosp inal irradiation with a local boost to the primary tumor and patient r andomization to receive adjuvant chemotherapy with either 1) CCNU, vin cristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Cent ralized review of the tumor pathological characteristics revealed 20 e pendymomas and 12 anaplastic ependymomas in the 32 children included i n the study. Diagnoses made at the individual institutions included an aplastic (malignant) ependymoma (15 patients), ependymoma (four patien ts), ependymoblastoma (nine patients), ependymoastrocytoma (one patien t), and primitive neuroectodermal tumor (three patients), which were d iscordant with the centralized review diagnosis in 22 of 32 cases. Onl y three of the 32 patients had metastatic disease (two with M1 and one with M3 stages). At surgery, 47% of tumors were estimated to be total ly resected. Among the 14 of 17 patients who suffered a relapse and we re evaluated for site of relapse, 10 (71%) had an isolated local relap se, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates wer e 50 +/- 10% and 64 +/- 9%, respectively. Conclusions. Predictors of P FS duration included an estimate of the extent of resection made at su rgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (less than or equal to 1.5 cm(2) compared with > 1.5 cm(2), p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T ) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominan tly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of ou tcome of ependymoma. Survival rates were comparable with those reporte d by other investigators who have treated patients with similar doses of radiation and no chemotherapy.