Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor

Abstract

Purpose: The Sixth International Society of Pediatric Oncology study (SIOP6) concerned Wilms' tumor with favorable histology, preoperatively treated to obtain a high rate of stage I patients, and sought to reduce treatment for patients with stage I and stage II negative nodes (IIN0) tumors and to find better therapy to prevent relapses in stage II positive nodes (IIN1) and stage III patients.

Patients and methods: Eligible patients (N = 509) had received four weekly doses of vincristine (VCR) and two courses of dactinomycin (AMD) preoperatively and were assigned after surgery, according to stage and lymph node involvement, to three different prognostic groups, which were to be randomized. Stage I patients (n = 303) received VCR and AMD either for 17 weeks (S) or 38 weeks (L). Stage IIN0 patients (n = 123) received either 20 Gy irradiation (R+) or no irradiation (R-) and received VCR and AMD for 38 weeks. Stage IIN1 and III patients (n = 83) received intensified VCR and AMD (INTVCR) versus VCR, AMD, and Adriamycin (ADRIA; Doxorubicin Farmitalia Carbo Erba, Rueil, Malmaison, France; doxorubicin). Assessment criteria were 2-year disease-free survival (DFS) and 5-year survival (SURV) percentages. A stopping rule was added that took into account abdominal recurrences for the stage IIN0 trial.

Result: A 52% rate of stage I tumors was obtained, with a low rate of ruptures (7%). The 2-year DFS and 5-year SURV rates according to the different therapeutic groups were stage I, 92% versus 88% (equivalent) and 95% versus 92% for S and L, respectively; stage IIN0, 72% versus 78% (stage equivalent) and 88% versus 85% for R+ and R-, respectively; and stage IIN1 and stage III, 49% versus 74% (P < .029) and 77% versus 80% for INTVCR and ADRIA, respectively, which results in an 82% DFS and 89% SURV rate for the entire trial population. However, six abdominal metastases observed during the first year of follow-up (FU) in the R- group versus none in the R+ group resulted in discontinuation of the stage IIN0 trial.

Conclusion: Risk-adapted therapy to limit risk of sequelae is possible. More intensive chemotherapy is necessary to prevent abdominal recurrences in nonirradiated stage IIN0 patients treated preoperatively. A three-drug protocol is necessary in stage IIN1 and stage III patients.