Supratentorial Primitive Neuroectodermal Tumors in Young Children

TO THE EDITOR: In the April issue of the Journal of Clinical Oncology, Timmermann et al suggest that radiotherapy plays a major role in the treatment of young children with supratentorial primitive neuroectodermal tumors (stPNET) and conclude that a delay in irradiation may compromise survival. Although stPNET are undoubtedly aggressive brain tumors and results of treatments are still disappointing, the conclusions of Timmermann et al should be considered with caution. Twenty-nine children younger than 37 months were diagnosed with stPNET and were registered in these consecutive multiinstitutional protocols. The protocols used two different chemotherapy regimens, and recommendations regarding radiation were fundamentally different between HIT-SKK87 (all patients received systematic radiation at the age of 3 years, or earlier with progression) and HIT-SKK92 (radiation for patients 18 months old with recurrence/progression). The 3-year overall survival and progression-free survival of 17.2% and 14.9% of patients, respectively, are in agreement with previous reports from cooperative groups. Five children were disease-free survivors (including four who received craniospinal irradiation [CSI]), and radiation therapy was a statistically significant factor for survival. Based on their experience, the authors recommend whole CNS irradiation (54 Gy to the tumor bed, 35 Gy CSI) and also advise limiting the delay of radiation to a maximum of 6 months. The arguments of Timmermann et al are based on solid evidence that stPNET in infants has an aggressive behavior. However, their conclusions regarding the role of prophylactic radiation may be flawed, as they analyzed the impact of radiation after the fact. Almost every child whose parents, or treating physicians, refused irradiation for their children had early disease progression (14 of 15 patients). Conversely, the median time to progression was longer in the group that underwent radiation. Prophylactic radiation was offered for 10 children in remission at completion of chemotherapy. This certainly represents a subgroup of patients whose tumors behaved unusually, and one may wonder whether some of these patients who received radiation may have been overtreated. Only intent-to-treat statistics may help to refine the conclusions of this study. In addition, detailed information on the five survivors is lacking, in particular their neurocognitive assessments. The morbidity related to CSI in very young children is well documented. Walter et al reported a median IQ of 62 (44 to 86) at 5 years in a cohort of 19 young children with medulloblastoma who received CSI at a median age of 3.3 years. As stPNET are located supratentorially, concerns regarding long-term effects of radiation are even more important, as the size of these tumors is often considerable and the morbidity of a boost greater than 50 Gy is a major issue. In the absence of measurable data on neurointellectual outcome, the conclusions and recommendations of Timmermann et al should be considered with extreme caution, since the decision to avoid or delay standard-dose CSI in infants is primarily based on the unacceptable long-term morbidity of this treatment modality in this specific population. Long-term survival without radiation therapy has been reported using intensive or high-dose chemotherapy with stem cell rescue. Although the success observed with chemotherapy only is still low, new strategies are currently under investigation to improve these results. The recommended use of standard-dose CSI may represent a step back after 20 years of experience using and developing “baby brain” strategies.