Veno-occlusive disease of the liver in children treated for Wilms tumor

Hepatotoxicity consistent with the clinical diagnosis of veno-occlusive disease (VOD) of the liver has been suspected after conventional anti-cancer chemotherapy in children. To establish the incidence of hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained on 511 children affected by Wilms tumor and treated according to the SIOP-9 protocol. They all received pre- and postnephrectomy chemotherapy using dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy according to surgical stage and histology. Sixty-four patients suffered at least one episode of hepatotoxicity and 41 satisfied the criteria for a clinical diagnosis of VOD. In this latter group, toxicity occurred during preoperative treatment in 15 patients and was confirmed histopathologically in 9 of the 16 liver biopsies obtained. There was a higher percentage of children aged less than 1 year at diagnosis in the VOD group than in the other patients (24% vs. 11.4%). The degree of liver damage in the younger patients seems important, as suggested by a higher increase in transaminases. VOD developed in 12% of the 68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis showed an increased risk of VOD in younger patients (p < 0.001) and in those receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using supportive therapy only. (1) 8% of children treated according to the SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients who received radiotherapy, the incidence was 6%. These figures are much higher than in earlier reports, though different diagnostic criteria were used. (2) Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors are young age and concomitant radiotherapy. (4) VOD does not prejudice positive outcome for these patient

Glomerular filtration rate and prevalence of chronic kidney disease in Wilms’ tumour survivors

Glomerular filtration rate (GFR) was evaluated in 32 Wilms’ tumour survivors (WTs) in a cross-sectional study using 99 Tc-diethylene triamine pentaacetic acid (99 Tc-DTPA) clearance, the Schwartz formula, the new Schwartz equation for chronic kidney disease (CKD), cystatin C serum concentration and the Filler formula. Kidney damage was established by beta-2-microglobulin (B-2-M) and albumin urine excretion, urine sediment and ultrasound examination. Blood pressure was measured. No differences were found between the mean GFR in 99 Tc-DTPA and the new Schwartz equation for CKD (91.8 ± 11.3 vs. 94.3 ± 10.2 ml/min/1.73 m2 [p = 0.55] respectively). No differences were observed between estimated glomerular filtration rate (eGFR) using the Schwartz formula and the Filler formula either (122.3 ± 19.9 vs. 129.8 ± 23.9 ml/min/1.73 m2 [p = 0.28] respectively). Increased urine albumin and B-2-M excretion, which are signs of kidney damage, were found in 7 (22%) and 3 (9.4%) WTs respectively. Ultrasound signs of kidney damage were found in 14 patients (43%). Five patients (15.6%) had more than one sign of kidney damage. Eighteen individuals (56.25%) had CKD stage I (10 with signs of kidney damage; 8 without). Fourteen individuals (43.75%) had CKD stage II (6 with signs of kidney damage; 8 without). The new Schwartz equation for CKD better estimated GFR in comparison to the Schwartz formula and the Filler formula. Furthermore, the WT survivors had signs of kidney damage despite the fact that GFR was not decreased below 90 ml/min/1.73 m2 with 99 Tc- DTPA

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

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours-the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in childre

The role of preoperative chemotherapy in the management of Wilms' tumor. The SIOP studies. International Society of Pediatric Oncology

More than 25 years after introducing preoperative chemotherapy for Wilms' tumor, the benefits of this approach are well known. The preoperative protocol results in easier operations with significantly fewer tumor ruptures during surgery and a favorable stage distribution. Acute toxicity and late effects are minimized without jeopardizing disease-free and overall survival. Future clinical trials of Wilms' tumor should seek additional risk factors to stratify and individualize treatment. These prognostic factors will improve the cure rates for high-risk patients by intensifying therapy and the quality of life for children with more favorable prognosis by lowering therapy to a minimum. As is true for radical surgery, partial nephrectomy in unilateral disease must be evaluated in carefully selected patients according to clear and well-defined indications. Molecular genetic studies should increase understanding of Wilms' tumor, influencing treatment and outcom

Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial

Background Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. Methods Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. Findings By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). Conclusions Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health cost