paediatrics Brussels 17

Bifractionated RT in childhood ependymoma d C. C ONTER et al .

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( i.e., carboplatin, etoposide, vincristine, and ifosfamide) was followed by 70.7-Gy bifractionated RT. Similarly, Massi- mino et al. (16) reported on the Associazione Italiana di Ematologia-Oncologia Pediatrica strategy using vincristine, etoposide, and cyclophosphamide with HFRT at a dose of 70.4 Gy, with a 5-year OS rate of 75% and a PFS rate of 56%. Their results were also very encouraging, with 9 of 12 responses to RT and 15 of the 23 relapses being local. In the present study, the 5-year OS (74.8%) and PFS (54.2%) rates were roughly similar, despite lower radiation doses (range, 60–66 Gy) and the lack of associated chemo- therapy. The rate of response to RT was 3 of 4 and most (10 of 11) relapses were local. However, the administration of HFRT is more complicated than standard RT. Only one- third of our patients could receive RT within the first 30 days after surgery. This delay was not just related to postop- erative complications. Whether monofractionated RT would have resulted in shorter delays is not clear. Most recent stud- ies have used standard local or craniospinal (21) or conformal RT (26) . The 5-year OS rate was 65–76%, and the PFS rate was 50–75% (16, 18, 21, 27–29) . The results of the five major studies are reported in Table 4 . The most encouraging results have been reported by Merchant et al. (26) . This unicentric study also included young patients (median age, 2.8 years). The high rate of complete surgical removal obtained in the present study might have been because of the high number of second-look surgeries. The rate and type of postoperative complications have not been clearly reported. The 1-cm safety margin is small and requires perfect immobilization of the patient. The RT procedures are very sophisticated and thus often require general anesthesia, which can be 1. Pollack IF. Brain tumors in children. N Engl J Med 1994;331: 1500–1507. 2. Allen JC, Siffert J, Hukin J. Clinical manifestations of child- hood ependymoma: A multitude of syndromes. Pediatr Neuro- surg 1998;28:49–55. 3. Wilne S, Collier J, Kennedy C, et al . Presentation of childhood CNS tumours: A systematic review and meta-analysis. Lancet Oncol 2007;8:685–695. 4. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, et al . Adju- vant chemotherapy of childhood posterior fossa ependymoma: Cranio-spinal irradiation with or without adjuvant CCNU, vin- cristine, and prednisone—A Children’s Cancer Group study. Med Pediatr Oncol 1996;27:8–14. 5. Carrie C, Muracciole X, Gomez F, et al . Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk me- dulloblastoma without chemotherapy: Results of the French M-SFOP 98 protocol. Int J Radiat Oncol Biol Phys 2005; 63:711–716. 6. Needle MN, Goldwein JW, Grass J, et al . Adjuvant chemother- apy for the treatment of intracranial ependymoma of childhood. Cancer 1997;80:341–347. 7. Mulhern RK, Merchant TE, Gajjar A, et al . Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 2004;5:399–408. 8. Geyer JR, Sposto R, Jennings M, et al . Multiagent chemother- apy and deferred radiotherapy in infants with malignant brain

difficult to perform in a multi-institutional setting. The 3-year PFS findings have been reported, and longer follow- up is needed to ensure that relapse will not occur. Whether such encouraging results will be confirmed by the multi- institutional ACNS 0121 Children’s Oncology Group study remains to be demonstrated. The major concern with RT delivered to young children is long-term neuropsychological and endocrine sequelae. It is difficult to compare series that do not always prospectively report such complications and for which no follow-up data are available. Grill et al. (30) reported that 11 patients with EP who underwent local RT of the whole posterior fossa at 55 Gy had a mean full-scale IQ of 84.2, with the verbal IQ superior to performance IQ. Of these 11 patients, 94% were able to attend normal school- ing (30) . Our series showed that about three-quarters of long- term survivors were free of neuropsychological, endocrine, or hearing troubles and have normal school results. The visual sequelae are mostly strabismus, which is more likely a result of surgery than to RT. The results of the present study have demonstrated that local HFRT is feasible for the treatment of EP. Whether the low rate of long-term sequelae resulted from the procedure remains to be demonstrated. Only one-half of the children treated were cured. Whether standard 59.4 Gy will result in greater PFS at 5 years also remains to be clarified. Moreover, the role of adjuvant treatment by chemotherapy or innovative treatments deserves additional randomized evaluation. tumors: A report from the Children’s Cancer Group. J Clin Oncol 2005;23:7621–7631. 9. Grill J, Le Deley MC, Gambarelli D, et al . Postoperative chemo- therapy without irradiation for ependymoma in children under 5 years of age: A multicenter trial of the French Society of Pedi- atric Oncology. J Clin Oncol 2001;19:1288–1296. 10. Grundy RG, Wilne SA, Weston CL, et al . Primary postopera- tive chemotherapy without radiotherapy for intracranial epen- dymoma in children: The UKCCSG/SIOP prospective study. Lancet Oncol 2007;8:696–705. 11. Louis DN, Ohgaki H, Wiestler OD, et al . The 2007 WHO clas- sification of tumours of the central nervous system. Acta Neuro- pathol (Berl) 2007;114:97–109. 12. Gnekow AK. for the SIOP Brain Tumor Subcommittee, Interna- tional Society of Pediatric Oncology. Recommendations of the Brain Tumor Subcommittee for the reporting of trials. Med Pediatr Oncol 1995;24:104–108. 13. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996;17:343–346. 14. Bouffet E, Perilongo G, Canete A, et al . Intracranial ependymo- mas in children: A critical review of prognostic factors and a plea for cooperation. Med Pediatr Oncol 1998;30:319–329. 15. Smyth MD, Horn BN, Russo C, et al . Intracranial ependymo- mas of childhood: current management strategies. Pediatr Neu- rosurg 2000;33:138–150. 16. Massimino M, Gandola L, Giangaspero F, et al . Hyper- fractionated radiotherapy and chemotherapy for childhood CONCLUSION

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