Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

Green, D M; Breslow, Norman E.; Beckwith, J. Bruce; Finklestein, J Z; Grundy, Paul E.; Thomas, Patrick R.; Kim, T; Shochat, Stephen J.; Haase, Gerald M.; Ritchey, Michael L.; Kelalis, Panayotis P.; D’Angio, Giulio J.

doi:10.1200/jco.1998.16.12.3744

Cited by 151 publications

(75 citation statements)

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“…[7][8][9] Survival from Wilms' tumour has been increasing over the past 40 years, while, paradoxically, the overall duration and intensity of treatment has been decreasing for most patients. 2,4 This fi nding suggests that further treatment reductions could be possible for many patients.…”

Section: Introductionmentioning

confidence: 95%

“…1 Treatment of localised, non-anaplastic Wilms' tumour, which accounts for nearly three-quarters of all cases, is highly successful, with a cure rate of almost 90%. [2][3][4][5] Treatment consists of nephrectomy and chemotherapy, together with radiotherapy when the tumour is classifi ed Overall, 33-40% of all patients with unilateral, localised, non-anaplastic Wilms' tumour receive doxorubicin. 3,5,6 In the setting of such a highly curable childhood cancer, the reduction of potential harm from irreversible side-eff ects of treatment is of paramount importance to improve overall outcomes.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2015

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BACKGROUND: Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. METHODS: For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 g/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. FINDINGS: Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year eventfree survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…This favorable outcome occurred despite reductions in the length of therapy, dose of radiation, extent of fields irradiated, and percentage of patients receiving radiation therapy. 42,43 Unfortunately, patients with anaplastic Wilms tumors have not benefited from advances in therapy to the same extent as those with more favorable histology.…”

Section: Renal Tumors (Wilms)mentioning

confidence: 99%

Outcomes for Children and Adolescents With Cancer: Challenges for the Twenty-First Century

Smith

Seibel

Altekruse

et al. 2010

JCO

897

684

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A B S T R A C T PurposeThis report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research discoveries on outcome and provide essential information for prioritizing future research directions. MethodsIncidence and survival data for childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause. ResultsChildhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to 1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers studied, with the extent and temporal pace of the increases varying by diagnosis. ConclusionWhen 1975 age-specific death rates for children are used as a baseline, approximately 38,000 childhood malignant cancer deaths were averted in the United States from 1975 through 2006 as a result of more effective treatments identified and applied during this period. Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased understanding of the molecular processes that promote growth and survival of specific childhood cancers.

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“…Any patient deemed to have lung metastases was given whole-lung irradiation. The 2-year www.TheOncologist.com relapse-free survival estimate for patients with stage IV disease treated on NWTS-4 was 81% [52]. In the SIOP studies, only chest x-ray was used to evaluate lung metastasis.…”

Section: Pros and Cons Of The Nwtsg And Siop Approachesmentioning

confidence: 99%

Current Therapy for Wilms’ Tumor

2005

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Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

Abstract: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Cited by 151 publications

References 14 publications

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

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

Outcomes for Children and Adolescents With Cancer: Challenges for the Twenty-First Century

Current Therapy for Wilms’ Tumor

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