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Journal of Clinical Oncology, Vol 24, No 21 (July 20), 2006: pp. e41 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.06.8882
Treatment Complications in Neuroblastoma Patients: Lessons From Screening StudiesDepartment of Pediatrics and Adolescent Medicine, Medical University, Graz, Austria
St Anna Children's Hospital, Vienna, Austria
Children's Cancer Research Institute, Vienna, Austria To the Editor: In the April 1, 2006, issue of the Journal of Clinical Oncology, Barrette et al1 reported treatment complications in neuroblastoma patients diagnosed by urinary mass screening between 1989 and 1994. They reported a strikingly high rate of severe sequelae in 11 of 45 patients, although the majority of their patients had low-stage tumors or stage 4s. In the Austrian screening study performed between 1991 and 2003, a similar number of children were screened (439,128 children), and 60 neuroblastomas were detected. In our study2, the rate of serious complications was substantially lower and only seven of 60 patients had similar complications like those described by Barrette et al. 1 This difference is most likely a consequence of two different study periods (1989 to 1994 in the Quebec study, 1991 to 2003 in the Austrian study). In our study2, the majority of serious complications occurred in the early stage between 1991 and 1996. Much to our regret there were even two therapy related deaths (1991 and 1994) in children who were diagnosed with neuroblastoma by mass screening (one death due to hemorrhagic shock after surgery and one death due to cytotoxic therapy). The findings of Barrette et al1 and our own observations underline the need for a patient-tailored treatment in neuroblastic tumors, which has become more and more adopted in recent years and is based predominantly on biological features.3 It includes the potential nontreatment of localized neuroblastomas and a more restrictive behavior concerning cytotoxic therapy in localized neuroblastomas with favorable biologic features.4,5 Whereas treatment strategy for neuroblastomas was rather aggressive 10 years to 15 years ago (in the study of Barrette et al1 all patients with stage B received cytotoxic therapy), this behavior has changed greatly. Pediatric oncologists, as well as pediatric surgeons, have learned that in many cases (especially in screening cases and incidentally diagnosed localized neuroblastomas) an aggressive approach that eventually compromises vital organs or even life is not justified. Therefore, observations like that made by Barrette et al1 will probably not occur to that extent in the future for low stage and 4s neuroblastoma cases. In contrast, also a too restrictive approach might be disadvantageous for individual patients. In our screening study2, treatment delay in one patient (due to consideration of spontaneous regression of a localized paravertebral tumor) resulted in excessive tumor growth and finally the loss of one kidney. Another localized tumor which was MYCN-negative by needle biopsy turned out to consist also of MYCN-amplified sections, and a delay of treatment could have been fatal for this patient.2,6 We agree with Barrette et al that it might be better not to know about a tumor which is biologically scheduled to regress or mature, and consequently all neuroblastoma screening programs worldwide were discontinued. However, there remain a great number of incidentally diagnosed neuroblastomas. It is still a matter of debate how to manage such cases, especially if complete resection appears to be difficult. Whereas it has become common practice to avoid life-threatening surgery, no other generally accepted guidelines for the (non)treatment of such neuroblastomas do exist. Overall, the use of cytotoxic therapy has however become more restrictive in recent years. Unfortunately, no noninvasive parameters are available to reliably predict the biologic behavior of an individual tumor. It is a challenge for pediatric oncologists and pediatric surgeons to carefully balance the risks of treatment against the risks of tumor progression, dissemination, and relapse. Complete resection at any price appears no longer justified while the wait and see strategy represents an option for selected patients. For untreated cases and incompletely resected neuroblastomas, however, a close follow-up is mandatory in order to avoid potential harm from tumor progression or dissemination. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. ACKNOWLEDGMENTS The Austrian Neuroblastoma Screening Study was supported by the Styrian Government, the Styrian Children's Cancer Fund and the Children's Cancer Research Institute, Vienna, Austria. REFERENCES
1. Barrette S, Bernstein ML, Leclerc JM, et al: Treatment complications in children diagnosed with neuroblastoma during a screening program. J Clin Oncol 24:1542-1545, 2006 2. Kerbl R, Urban CE, Ambros IM, et al: Neuroblastoma mass screening in late infancy: Insights into the biology of neuroblastic tumors. J Clin Oncol 21:4228-4234, 2003 3. Ambros IM, Benard J, Boavida M, et al: Quality assessment of genetic markers used for therapy stratification. J Clin Oncol 21:2077-2084, 2003 4. Kerbl R, Urban CE, Lackner H, et al: Connatal localized neuroblastoma: The case to delay treatment. Cancer 77:1395-1401, 1996[CrossRef][Medline] 5. Yamamoto K, Hanada R, Kikuchi A, et al: Spontaneous regression of localized neuroblastoma detected by mass screening. J Clin Oncol 16:1265-1269, 1998 6. Ambros PF, Ambros IM, Kerbl R, et al: Intratumoural heterogeneity of 1p deletions and MYCN amplification in neuroblastomas. Med Pediatr Oncol 36:1-4, 2001[CrossRef][Medline]
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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