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 Green, D. Search for Related Content PubMed Articles by Green, D. Related Articles Related Correspondence Social Bookmarking                            What's this?

In Reply:

Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY

I appreciate the thoughtful comments of Drs de Kraker and Pritchard-Jones. The primary goal of the review that I wrote was to update the results of several prior National Wilms Tumor Study Group trials. I incorporated the results of randomized trials conducted by both the United Kingdom Children's Cancer Study Group (UKCCSG) and the International Society of Pediatric Oncology (SIOP) within the limitations of length for an original article. I apologize if the discussion appeared to give incomplete attention to the work of these two groups, but do not feel that the data from their studies were quoted inaccurately.

de Kraker and Pritchard-Jones refer to the results of a recently completed UKSSCG study¹ that has been presented in only abstract form. In this trial, 10.2% of randomly assigned patients (21 of 205) had a different malignant or a benign tumor. The size of the eligible population from which these 205 randomly assigned patients were drawn was not reported in the abstract. Certainly the results of this study may contribute valuable data to the ongoing discussion of the relative merits of immediate versus delayed nephrectomy. However, the complete study results must be available in a peer-reviewed journal for this value to be realized. de Kraker and Pritchard-Jones state that "adoption of the UK approach of initial biopsy even in children with typical clinical and imaging features of Wilms tumor...does not appear to be associated with an increased risk of local recurrence or upstaging." However the manuscript by Vujanic et al² that is referred to includes no data regarding the relationship between biopsy and either flank or intra-abdominal relapse rate. Nor does he include data comparing these rates to those obtained by investigators from SIOP in comparable patients who were managed without initial tumor biopsy.

de Kraker and Pritchard-Jones refer to the" loss of staging information" as a potential advantage of prenephrectomy chemotherapy. However children with stage II, lymph node-negative tumors randomly assigned in SIOP-6 to receive or not receive postnephrectomy abdominal irradiation had a significantly increased rate of intra-abdominal tumor recurrence, necessitating premature closure of that arm of the study.³ Subsequently SIOP investigators have administered an anthracycline to all such patients because they felt two-drug chemotherapy with only vincristine and dactinomycin, in the absence of abdominal irradiation, was inadequate therapy for this group of patients.⁴ The increased intra-abdominal relapse rate in SIOP-6 suggests that staging information was in fact lost as the result of prenephrectomy chemotherapy administration.

de Kraker and Pritchard-Jones review the prior NWTSG recommendation for whole lung irradiation of all children with pulmonary metastases. In the review, I emphasized that the results of SIOP and the NWTSG were similar and suggested that a trial of therapy of such patients either without an anthracycline or without whole-lung irradiation might be appropriate. This suggestion would be supported by the results of a recent analysis conducted by the UKCCSG.⁵

Identification of factors that define that subgroup of patients whose outlook is sufficiently poor that administration of more aggressive treatment with the attendant increased risk of therapy related morbidity and mortality is a goal of all who investigate the treatment of children with Wilms tumor. As pointed out by de Kraker and Pritchard-Jones, loss of heterozygosity for markers at 1p and/or 16q identifies approximately one third of patients with unilateral, nonmetastatic tumors as high risk.⁶ The SIOP investigators propose treatment intensification only for those with tumor histology in the "newly defined high-risk category," which includes, according the manuscript by Weirich et al,⁷ those tumors with predominant blastemal, mixed, and predominant regressive changes that have a reduction in volume of less than 40% following prenephrectomy chemotherapy. These represent approximately one quarter SIOP patients with unilateral, nonmetastatic Wilms tumor. Further research is required to identify new treatment stratification factors that are sufficiently specific to justify treatment of those children with adverse prognostic factors with therapy of significantly increased intensity. It will be important to evaluate the cost of various treatment strategies both in terms of the short-term costs, such as those for sophisticated laboratory evaluations, as well as the long-term costs, such as those due to anthracycline-related cardiomyopathy and other treatment related-related complications.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Mitchell C, Shannon R, Vujanic G, et al: The treatment of Wilms Tumour: The United Kingdom Children's Cancer Study Group Third Wilms Tumor Study. Med Pediatr Oncol 14:287, 2003 (abstr O119)

2. Vujanic GM, Kelsey A, Mitchell C, et al: The role of biopsy in the diagnosis of renal tumors of childhood: Results of the UKCCSG Wilms Tumor Study 3. Med Pediatr Oncol 40:18-22, 2003[CrossRef][Medline]

3. Tournade MF, Com-Hougue C, Voute PA, et al: Results of the sixth International Society of Pediatric Oncology Wilms tumor trial and study: A risk-adapted therapeutic approach in Wilms' tumor. J Clin Oncol 11:1014-1023, 1993[Abstract/Free Full Text]

4. Tournade MF, Com-Hougue C, de Kraker J, et al: Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: Results of the ninth International Society of Pediatric Oncology Wilms tumor trial and study. J Clin Oncol 19:488-500, 2001[Abstract/Free Full Text]

5. Nicolin G, Taylor R, Shannon R, et al: The potential benefit of pulmonary radiotherapy in Wilms' tumour patients with pulmonary metastases—A UKCCSG Wilms' Tumour Working Group Study. Med Pediatr Oncol 41:291, 2003 (abstr O141).

6. Grundy PE, Telzerow PE, Breslow N, et al: Loss of heterozygosity for chromosomes 16q and 1p in Wilms tumors predicts an adverse outcome. Cancer Res 54:2331-2333, 1994[Abstract/Free Full Text]

7. Weirich A, Leuschner I, Harms D, et al: Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH. Ann Oncol 12:311-319, 2001[Abstract/Free Full Text]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Treatment of Wilms Tumor: An International Perspective
  Jan de Kraker and Kathy Pritchard Jones
  JCO 2005 23: 3156-3157 [Full Text]

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 Green, D. Search for Related Content PubMed Articles by Green, D. Related Articles Related Correspondence Social Bookmarking                            What's this?