Adjuvant Chemotherapy for Ependymoma: Is It Necessary for All Children Under Five Years of Age?
Authors: Arnold C. Paulino, John M. Buatti, Jacques Grill, Chantal Kalifa
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.15.3588 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11481371 Adjuvant Chemotherapy for Ependymoma: Is It Necessary for All Children Under Five Years of Age? Arnold C. PaulinoxArnold C. PaulinoSearch for articles by this author , John M. BuattixJohn M. BuattiSearch for articles by this author Jacques GrillxJacques GrillSearch for articles by this author , Chantal KalifaxChantal KalifaSearch for articles by this author Show More University of Iowa College of Medicine, Iowa City, IAInstitut Gustav Roussy, Villejuif, France https://doi.org/10.1200/JCO.2001.19.15.3588 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01082001In Reply:We thank Drs Paulino and Buatti for their comments on our article.1 Their remarks fuel the controversy over the usefulness of adjuvant treatment in children with ependymoma. Our data show unequivocally that irradiation can be delayed until a possible relapse in children with complete resection confirmed by an early postoperative computed tomography (CT) or magnetic resonance imaging (MRI) scan. With this approach, approximately one fourth of the patients did not receive any radiation treatment at all, and in patients who required irradiation, this treatment was deferred for a median period of 11/2 years. These are the most important messages we want to get across to clinicians.Paulino and Buatti raised the question of the need for adjuvant chemotherapy in all of these patients. We stated in the article that no radiologic response to adjuvant chemotherapy could be documented in children with a postoperative residue. As this type of chemotherapy was unable to control macroscopic disease, did it really control microscopic disease, or was chemotherapy unnecessary for these children, as stated by Paulino and Buatti? We think that our data cannot resolve these questions. However, given our results and the data from small series in the literature in which patients with ependymoma were cured by surgery alone, a randomized study could be proposed comparing adjuvant chemotherapy to no chemotherapy in children with totally resected ependymomas. However, a lot of children in whom initial resection was complete (verified by early postoperative imaging, and whatever the initial tumor site) did relapse, and this would argue against such a randomized trial with no adjuvant treatment in one arm.In our study, 13 children had a supratentorial ependymoma (one low-grade and 12 high-grade tumors). Seven had a complete resection confirmed by early imaging. Five of these seven patients relapsed 9 to 42 months after the initiation of chemotherapy and received irradiation as part of the salvage therapy. At the last follow-up visit, five out of the seven children were alive in complete remission (CR) (two in CR1 and three in CR2) 21 to 87 months after the initiation of chemotherapy. Sixty children had an infratentorial ependymoma. Thirty-seven had a complete resection that was confirmed by early imaging. Twenty-five of the thirty-seven children developed a recurrence 5 to 45 months after the initiation of chemotherapy and received irradiation as part of their salvage regimen. At the last follow-up visit, 20 were alive in CR (12 in CR1 and eight in CR2) 9 to 89 months after the initiation of chemotherapy.The fact that more than 60% of children with a radiologically confirmed complete resection developed a recurrence despite adjuvant chemotherapy probably signifies that more efficient adjuvant treatment is needed. If we want to spare these children the deleterious effects of irradiation at a young age, we must develop more effective chemotherapy.In conclusion, we think that we should try to better define the proportion of patients who did not relapse after initial complete resection. Once these patients are accurately defined, the question of the usefulness of adjuvant treatment could be examined in this subset of patients. A better adjuvant chemotherapy protocol has to be found for patients at risk of relapse despite initial complete resection.The high proportion of high-grade tumors in our series may reflect a referral bias, because only children sent to the medical oncologist for adjuvant treatment were eligible for the trial. In the case of completely resected low-grade tumors, the neurosurgeons may have chosen a wait-and-see policy. On the other hand, as mentioned by Paulino and Buatti, grading may vary between the pathologists in the absence of clearly defined and reproducible grading procedures. We have tried to avoid this problem by applying a systematic central review of the slides for histologic diagnosis and grading.It is obvious that adjuvant treatment may be useful for children with incomplete initial resection. However, the Baby French Society of Pediatric Oncology regimen is not sufficiently potent for these patients, since all the children with a residuum progressed during follow-up. At present, we cannot definitively state that all children with radiologically confirmed complete resection require adjuvant treatment, but most of them do. Again, the main message in our study is that the irradiation can be deferred and in some cases avoided in children with imaging-verified initial complete resection. Is this mild adjuvant chemotherapy the price all children have to pay? This may not be the case, but probably only a fraction of them can be cured with surgery alone.REFERENCE1. Grill J, Le Deley M-C, 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:: 1288,2001-1296, Link, Google Scholar