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In Reply

Division of Radiation Medicine, Paul Scherrer Institute, Villigen, Switzerland

Rolf-Dieter Kortmann

Department of Radiation Therapy, University Leipzig, Germany

Stefan Rutkowski

Children's University Hospital, University of Würzburg, Germany

We appreciate the interest of Dr Larouche and colleagues in our report on very young children with supratentorial primitive neuroecotodermal tumors (stPNET), and we would like to accentuate the conclusions of our initial report and the rationale behind them.

First, we agree completely that radiotherapy (RT) in young children with brain tumors is potentially harmful. In fact, we tried to emphasize the undisputable high risk of serious late effects associated with RT in young children. Herein lies the rationale for our approach of delaying or even avoiding RT in young children by introducing intensive chemotherapeutic regimen. Our conclusions on RT are based on a retrospective analysis, limiting the conclusiveness of our studies' results. Nevertheless there is no clear indication that patients who received prophylactic radiation were overtreated, especially because reports on sustained tumor control without RT are limited to very small patient numbers in the respective age group so far. Comparing children in remission who received prophylactic radiation (n = 10) with children in remission who received no prophylactic RT (n = 4; two without any RT, two receiving salvage RT), only three of 10 prophylactically radiated children survived. Furthermore, none of the four children in remission without prophylactic radiotherapy survived.

In addition, we consider the distinct differences in the results for the various tumor types treated by the same multimodal treatment protocols to be noteworthy. Despite the limited case numbers, evidence for a positive effect of radiotherapy on survival was observed in all subgroups of children with stPNET—children older than 3 years of age in the HIT88/91 study, children younger than 3 years in the HIT-SKK87/92 study, as well as the subgroup of children suffering from pineoblastoma.^1-3 In contrast, results were far better in children with early childhood medulloblastoma without radiotherapy,⁴ and complete tumor resection and initial tumor stage had higher impact than radiotherapy on survival in patients with ependymoma.^5,6

To our view, there is little evidence that radiotherapy can be avoided at present to achieve sustained tumor control in young children with stPNET. Trying to implement less intensive radiotherapy, we have increased the initial age for standard therapy from 3 to 4 years in the ongoing studies of the HIT group, and craniospinal irradiation is limited to 24 Gy. Clearly, craniospinal radiotherapy of 35 Gy is not recommended in any case for the treatment of very young children, as was alleged by Larouche et al.

We hope that effective "baby brain" strategies with further reduced, delayed, or omitted radiotherapy will be found in the future. We are also confident that increasing international cooperation in the research of rare pediatric tumors will contribute to improving the fate of our young patients.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Timmermann B, Kortmann RD, Kuhl J, et al: Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: Results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20:842-849, 2002[Abstract/Free Full Text]

2. Timmermann B, Kortmann RD, Kuhl J, et al: Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: Results of the German HIT-SKK87 and HIT-SKK92 trials. J Clin Oncol 24:1554-1560, 2006[Abstract/Free Full Text]

3. Hinkes BG, von Hoff K, Deinlein F, et al: Childhood pineoblastoma: Experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91. J Neurooncol doi:10.1007/s11060-006-9221-2[CrossRef][Medline]

4. Rutkowski S, Bode U, Deinlein F, et al: Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978-986, 2005[Abstract/Free Full Text]

5. Timmermann B, Kortmann RD, Kuhl J, et al: Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: Results of the German prospective trials HIT 88/89 and HIT 91. Int J Radiat Oncol Biol Phys 46:287-295, 2000[CrossRef][Medline]

6. Timmermann B, Kortmann RD, Kuhl J, et al: Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: Results of the prospective German brain tumor trials HIT-SKK 87 and 92. Radiother Oncol 77:278-285, 2005[CrossRef][Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Timmermann, B. Articles by Rutkowski, S. Search for Related Content PubMed Articles by Timmermann, B. Articles by Rutkowski, S. Social Bookmarking                            What's this?