Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial

Pritchard‐Jones, Kathy; Moroz, Veronica; Vujanić, Gordan; Powis, Mark; Walker, J. C. F.; Messahel, Boo; Hobson, Rachel; Levitt, Gill; Kelsey, Anna; Mitchell, Christopher

doi:10.1093/annonc/mds025

Cited by 81 publications

(80 citation statements)

References 17 publications

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“…Since the first SIOP protocol started in 1971, treatment intensity has been successfully reduced for the majority of patients with Wilms tumours, and survival has risen to 90% 2,[6][7][8][9][10] . Consequently, the identification of additional predictive and prognostic factors is increasingly important to improve the stratification of patients according to their individual risk.…”

Section: Treatment Recommendationsmentioning

confidence: 99%

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

et al. 2017

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Section: Treatment Recommendationsmentioning

confidence: 99%

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

et al. 2017

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“…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%

“…[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. [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.…”

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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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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“…Immediate tumour nephrectomy was performed in SIOP 93-01 and SIOP 2001 patients younger than 6 months or older than 18 years, and in patients treated according to AIEOP protocols unless the tumour was judged inoperable. The United Kingdom used a different national guideline for their patients included in the SIOP 2001 trial, including initial biopsy and intensified pre-operative chemotherapy if the biopsy revealed CCSK (Supplementary Table 1) (Mitchell et al , 2006; Stoneham et al , 2009; Pritchard-Jones et al , 2012). Administered post-operative treatment and applied radiotherapy per regimen is depicted in Supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study

et al. 2014

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Background:Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols.Patients and methods:We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012.Results:Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%–32%), and 5-year overall survival (OS) was 26% (95% CI: 10%–42%).Conclusions:In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

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Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial

Cited by 81 publications

References 17 publications

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

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

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

Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study

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