paediatrics Brussels 17

Conformal RT for Pediatric Ependymoma

and additional surgery at the completion of chemotherapy or time of progression could replace radiation therapy as treatment for ependymoma in 73 children younger than 5 years. 5 PFS estimates at 2 and 4 years were 33% and 22%, respectively; 50%of patients experienced relapse during the planned chemotherapy course. Radiation therapy was ulti- mately delivered to 39 patients (53%), but nearly 72% of patients with relapsed disease required further surgery and irradiation. At the time of their report, 34 patients (47%) had avoided irradiation, but only 11 were without evidence of disease and remained at high risk of progression. The median age of patients enrolled on the present study was 2.85 years, and their outcome has raised further questions about the necessity of chemotherapy and of ef- forts to delay or avoid irradiation. On the basis of our findings, the use of radiation therapy for pediatric patients of all ages (1 to 21 years) has been adopted by investigators from the Children’s Oncology Group. The current national trial for pediatric patients with localized ependymoma uses the targeting guidelines from this study and seeks to in- crease the proportion of cases in which gross-total resection is achieved, through the use of second surgery (Children’s Oncology Group ACNS0121).

37.5% 17% for the eight patients who were 0 to 23 months of age and 87.5% 12% for the eight patients who were 24 to 36 months old. Their findings suggested that the poor survival estimates frequently reported for young chil- dren were probably related to the delay in the administra- tion of radiation therapy, although tumor location and extent of resection were important cofactors. Preirradiation chemotherapy was shown to marginally effect PFS by univariate statistics in this report. The PFS after radiation therapy has been shown to be shorter for those treated with chemotherapy compared with those not treated with chemotherapy. 42,43 In the prospective Pediatric Oncology Group study, 3 those who received chemotherapy for 2 years had a worse PFS when compared with those who received chemotherapy for 1 year; however, because the Pediatric Oncology Group study did not have a radiation control arm, the effect seemed to be age-related. In our study, we had a sufficient number of young patients who did and did not receive chemotherapy so that we were able to perform univariate and multivariate analyses to show that age was not a factor and that preirradiation chemother- apy affects PFS by univariate statistics. The marginal signif- icance of this result leads us to believe that the 7-week course of chemotherapy for incompletely resected patients on the current Children’s Oncology Group study will not compromise PFS. The French Society of Pediatric Oncology conducted a study to determine whether postoperative chemotherapy

Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.

15. The Psychological Corporation: The Wechsler Individual Achievement Test. New York, NY, Harcourt, Brace, Jovanovich, 1992 16. Sparrow SS, Balla DA, Cicchetti DV: Vineland Adaptive Behavior Scales. Circle Pines, MN, American Guidance Services, 1984 17. Woodcock RW, Johnson MB: Woodcock- Johnson Tests of Cognitive Ability: Revised. New York, NY, Riverside Publishing, 1989 18. Xiong X: A class of sequential conditional probability ratio tests. J Am Stat Assoc 90:1463- 1473, 1995 19. Kaplan EL, Meier P: Nonparametric esti- mation from incomplete observations. J Am Stat Assoc 53:457-481, 1958 20. Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data. New York, NY, John Wiley & Sons, 1980 21. Cox DR: Regression models and life tables (with discussion). J R Stat Soc B 34:187-220, 1972 22. Gray RJ: A class of K-sample tests for comparing the cumulative incidence of a com- peting risk. Ann Stat 16:1141-1154, 1988 23. Verbeke G, Molenberghs G: Linear mixed models for longitudinal data. New York, NY, Springer-Verlag, 2000 24. SAS Institute Inc: SAS/STAT user’s guide, version 8. Cary, NC, SAS Institute, 1999 25. Rousseau P, Habrand JL, Sarrazin D, et al: Treatment of intracranial ependymomas of chil- dren: Review of a 15-year experience. Int J Radiat Oncol Biol Phys 28:381-386, 1994

7. Chao KS, Majhail N, Huang CJ, et al: Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tu- mor control in patients with oropharyngeal carci- noma: A comparison with conventional techniques. Radiother Oncol 61:275-280, 2001 8. Merchant TE, Zhu Y, Thompson SJ, et al: Preliminary results from a phase II trial of con- formal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma. Int J Radiat Oncol Biol Phys 52: 325-332, 2002 9. The Psychological Corporation: The Bayley Scales of Infant Development (ed 2). New York, NY, Harcourt, Brace, Jovanovich, 1993 10. The Psychological Corporation: The Wechsler Preschool and Primary Scales of Intel- ligence: Revised. San Antonio, TX, Harcourt, Brace, Jovanovich, 1989 11. The Psychological Corporation: The Wechsler Intelligence Test for Children (ed 3). New York, NY, Harcourt, Brace, Jovanovich, 1992 12. The Psychological Corporation: The Wechsler Adult Intelligence Scale: Revised. New York, NY, Harcourt, Brace, Jovanovich, 1989 13. Delis DC, Kramer JH, Kaplan E, et al: Califor- nia Verbal Learning Test: Children’s Version. New York, NY, Harcourt, Brace, Jovanovich, 1994 14. Delis DC, Kramer JH, Kaplan E, et al: California Verbal Learning Test. New York, NY, Harcourt, Brace, Jovanovich, 1987

REFERENCES 1. CBTRUS: Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Central Brain Tumor Registry of the United States, Hins- dale, IL, 2002 2. Merchant TE: Current management of childhood ependymoma. Oncology 16:629-644, 2002 3. Duffner PK, Horowitz ME, Krischer JP, et al: Postoperative chemotherapy and delayed ra- diation in children less than 3 years of age with malignant brain tumors. N Engl J Med 328:1725- 1731, 1993 4. Strother D, Kepner J, Aronin P, et al: Dose-intensive chemotherapy prolongs event- free survival for very young children with ependymoma: Results of Pediatric Oncology Group study 9233. Proc Am Soc Clin Oncol 19:585a, 2000 (abstr 2302) 5. Grill J, Le Delay MC, Gambarelli D, et al: Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: A multicenter trial of the French Society of Pediatric Oncology. J Clin Oncol 19:1288-1296, 2001 6. Zelefsky MJ, Fuks Z, Hunt M, et al: High- dose intensity modulated radiation therapy for prostate cancer: Early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 53:1111-1116, 2002

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