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

Abstract

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.

Omission of doxorubicin from the treatment of stage II–III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial

“…17 All other countries continued the well established SIOP approach of starting preoperative chemotherapy on the basis of clinical and imaging characteristics consistent with a diagnosis of Wilms' tumour, combined with measuring urinary catecholamines to exclude neuroblastoma, and reserving biopsy for cases with diagnostic dilemma. 2,18,19 Three-dimensional tumour volume was recorded at diagnosis and after completion of preoperative chemotherapy, according to whichever imaging method had been applied (ultrasonography, CT scan, or MRI scan). The calculated volume showed close correlation between methods (appendix).…”

“…Our data for stage II tumours are similar to a longer-term analysis of outcome of stage II tumours staged after immediate nephrectomy in the NWTSG 4 trial, 27 for which two-drug (vincristine plus actinomycin D) chemotherapy without doxorubicin was the standard after the NWTSG 3 trial. 19 This previous analysis focused on mechanical factors (tumour spill) to stratify stage II patients, whereas our study used in-vivo histological responses and would have placed tumours with spill into stage III. Encouragingly, our data suggest that stage III tumours can be treated eff ectively without doxorubicin, whereas the Children's Oncology Group recommend that tumours with spill should receive doxorubicin.…”

“…One of the trials (SIOP-6) 25 was excluded from the formal analysis because a 25% diff erence was noted between the study groups in cumulative dose of treatments other than anthracyclines. In the other study (National Wilms Tumor Study Group 3), 19 children were randomly assigned with a 2×2 factorial design that compared treatment with or without doxorubicin, and included random assignment to diff erent radiation doses of 10 or 20 Gy (K2 or DD2) in stage III, or 0 or 20 Gy in stage II Wilms' tumours, after immediate nephrectomy. None of the studies used histological assessment of the tumour as a stratifi cation technique.…”

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…Similar to the SIOP−2001 protocol, the UMBRELLA protocol continues to recommend preoperative actinomycin D and vincristine for patients newly diagnosed with Wilms tumour aged ≥6 months, based on results of previous SIOP trials that showed tumour downstaging using this regimen 2,6,8,9,14,17 . This benefit was also independently observed in the randomized, controlled UKW3 trial conducted by the UK Children's Cancer and Leukaemia Group (UKCCLG, previously known as the UK Children's Cancer Study Group) 18 .…”

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…The sixth SIOP study (conducted between 1980 and 1987), in which patients were treated with preoperative actinomycin and vincristine and postoperative actinomycin and vincristine with or without additional doxorubicin and/or radiotherapy, included only patients with a favourable-histology Wilms tumour (TABLE 1). Some 15 patients with CCSK were included in this study after initial misdiagnosis, but outcomes of these patients were not reported separately 27 . The SIOP 9 study (conducted between 1987 and 1991), including patients with nonmetastatic renal tumours, showed a substantial increase in EFS and OS of patients with CCSK after the addition of an anthracycline (epi rubicin or doxorubicin), an alkylating agent (ifosfamide), and radiotherapy to a dose of 30 Gy (in instances of local stage II and III disease) to the treatment protocol, resulting in a 2-year EFS of 75% and 5-year OS of 88% (n = 16; …”