Childhood Wilms Research Articles

Clinical Profile and Outcomes of Childhood Wilms Tumors Treated in a Tertiary Cancer Center from North India

In India and other lower-middle-income countries, the progress in the management of Wilms tumor (WT) has lagged behind when compared to the developed countries. In the current study, we highlight the outcomes of 61 children with WT treated at an oncological center in northern India. Our study found that the patient demographics, including age and gender distribution, closely paralleled other Indian studies. Notably, 24% of patients had distant metastasis at diagnosis. An upfront biopsy was performed in majority of the patient with a remarkable concordance rate of over 90%, with no significant complications associated with the procedure. Our surgical approach, guided by image-defined risk factors, resulted in 84% of patients undergoing delayed surgery after chemotherapy. Notably, the incidence of intraoperative complications, including tumor spill, was minimal. Treatment abandonment and toxic death due to sepsis emerged as significant challenges, affecting 22% and 7% of our patient cohort, respectively. The 3-year event-free survival (EFS) and overall survival were 70% and 84%, respectively. The age group of 6 to 8 years and stage V disease emerged as adverse factors influencing EFS. In summary, our study highlights the multifaceted nature of WT management in resource-constrained settings with survival rates promising but still lagging behind high-income countries. Addressing challenges such as treatment abandonment and reducing toxic death is imperative to enhance outcomes of WT in India.

Wilms Tumor in India: A Systematic Review.

Shyam SrinivasanBackground Cure rates of childhood malignancies are inferior in India compared with upper-middle-income countries. There is paucity of quality data addressing outcome of childhood Wilms tumor (WT) from India. This systematic review was conducted to assess the disease trends, treatment strategies, and outcome indicators in WT across India. Materials and Methods We conducted a systematic search of MEDLINE, Google Scholar, and SCOPUS database, and additionally screened International Society of Pediatric Oncology conference abstracts. Data concerning WT or nephroblastoma published from India were extracted. Results A total of 17 studies containing 1,170 patients were included in this review. Ninety-four percent of the studies were published after the year 2010. Advanced stage (III and IV) disease was seen in 46% of included patients. In seven studies, patients underwent a pretreatment biopsy before commencement of therapy. A hybrid approach consisting of "surgery first" in a selected subset and "neo-adjuvant chemotherapy" in all others was the most common treatment strategy adopted in half of the studies. The overall survival ranged between 48 and 89%. Key prognostic factors influencing survival across studies included increased tumor volume, metastatic disease, and unfavorable histology. Nonrelapse mortality (2.7-8.5%) was noted to be high. Conclusion Substantial proportion of children with WT from India present with advanced stages of the disease. Despite several limitations, the current systematic review showed a modest survival among Indian children with WT. Adopting strategies through collaboration to ensure early access to expert care along with involvement of social support team to improve compliance may further improve survival of WT in India.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Maternal lifestyle characteristics and Wilms tumor risk in the offspring: A systematic review and meta-analysis

BackgroundLittle is known about the etiology of childhood Wilms tumor (WT) and potentially modifiable maternal risk factors, in particular. MethodsUnpublished data derived from the hospital-based, case-control study of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) were included in an ad hoc conducted systematic literature review and meta-analyses examining the association between modifiable maternal lifestyle risk factors and WT. Eligible data were meta-analysed in separate strands regarding the associations of WT with (a) maternal folic acid and/or vitamins supplementation, (b) alcohol consumption and (c) smoking during pregnancy. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. ResultsEffect estimates from 72 cases and 72 age- and sex-matched controls contributed by NARECHEM-ST were meta-analysed together with those of another 17, mainly medium size, studies of ecological, case-control and cohort design. Maternal intake of folic acid and/or other vitamins supplements during pregnancy was inversely associated with WT risk (6 studies, OR: 0.78; 95 %CI: 0.69–0.89, I2 = 5.4 %); of similar size was the association for folic acid intake alone (4 studies, OR: 0.79; 95 %CI: 0.69-0.91, I2 = 0.0 %), derived mainly from ecological studies. In the Greek study a positive association (OR: 5.31; 95 %CI: 2.00–14.10) was found for mothers who consumed alcohol only before pregnancy vs. never drinkers whereas in the meta-analysis of the four homogeneous studies examining the effect of alcohol consumption during pregnancy the respective overall result showed an OR: 1.60 (4 studies, 95 %CI: 1.28–2.01, I2 = 0.0 %). Lastly, no association was seen with maternal smoking during pregnancy (14 studies, OR: 0.93; 95 %CI: 0.80–1.09, I2 = 0.0 %). ConclusionsIn the largest to-date meta-analysis, there was an inverse association of maternal folic acid or vitamins supplementation with WT risk in the offspring, derived mainly from ecological studies. The association with maternal alcohol consumption found in our study needs to be further explored whereas no association with maternal smoking was detected. Given the proven benefits for other health conditions, recommendations regarding folic acid supplementation as well as smoking and alcohol cessation should apply. The maternal alcohol consumption associations, however, should be further explored given the inherent limitations in the assessment of exposures of the published studies.

Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.

Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.

Mutations in microRNA processing genes in Wilms tumors derepress the IGF2 regulator PLAG1.

Many childhood Wilms tumors are driven by mutations in the microRNA biogenesis machinery, but the mechanism by which these mutations drive tumorigenesis is unknown. Here we show that the transcription factor pleomorphic adenoma gene 1 (PLAG1) is a microRNA target gene that is overexpressed in Wilms tumors with mutations in microRNA processing genes. Wilms tumors can also overexpress PLAG1 through copy number alterations, and PLAG1 expression correlates with prognosis in Wilms tumors. PLAG1 overexpression accelerates growth of Wilms tumor cells in vitro and induces neoplastic growth in the developing mouse kidney in vivo. In both settings, PLAG1 transactivates insulin-like growth factor 2 (IGF2), a key Wilms tumor oncogene, and drives mammalian target of rapamycin complex 1 (mTORC1) signaling. These data link microRNA impairment to the PLAG1-IGF2 pathway, providing new insight into the manner in which common Wilms tumor mutations drive disease pathogenesis.

Prospective analysis of long-term renal function in survivors of childhood Wilms tumor.

Considering the improved outcome, a better understanding of the late effects in Wilms tumor survivors (WT-S) is needed. This study was aimed at evaluating renal function and determining the prevalence of clinical and subclinical renal dysfunction in a cohort of WT-S using a multimodal diagnostic approach. Thirty-seven WT-S were included in this prospective cross-sectional single center study. To evaluate renal function, glomerular filtration rate (GFR) and urinary protein excretion were assessed. Additionally, kidney sonomorphology and blood pressure were analyzed. All examined WT-S (mean age 28.7 years, mean follow-up 24.8 years) had been treated with a combination of surgery and chemotherapy; 59.5% had received adjuvant radiotherapy. Impaired glomerular renal function was detected in a considerable proportion of WT-S, with age-adjusted cystatin-based GFR estimation below age norm in 55.9%. A lower cystatin-based estimated GFR (eGFR) correlated with longer follow-up time and higher irradiation dose. In 5 patients (13.5%) albuminuria was identified. Analysis of sonomorphology detected compensatory contralateral renal hypertrophy in 83.3% of WT-S. Chronic kidney disease (CKD) ≥ stage II was present in 55.9% of WT-S. Blood pressure measurements revealed arterial hypertension in 15 (40.5%) WT-S (newly diagnosed n=10). In 24.3% both CKD ≥ stage II and arterial hypertension were determined. Even though WT-S are believed to carry a low risk for end-stage renal disease, in this study, a remarkable number of WT-S presented with previously unidentified subclinical signs of renal function impairment and secondary morbidity. Therefore, it is important to continue regular follow-up, especially after transition into adulthood.

Nefroma mesoblástico congénito.

En el niño, el tumor renal más frecuente es el nefroblastoma o tumor de Wilms. Esto no sucede en el recién nacido o en el feto, aunque es cierto que en ellos se puede encontrar lesiones proliferativas que se parecen al tumor de Wilms, tales como la nefroblastomatosis, el nefroblastomas epitelial monomórfico y el nefroma mesoblástico (11) todos los cuales se agrupan bajo la denominación de congéneres infantiles del Wilms. En este grupo, un tumor que tiene características muy definidas, que es pertinente revisar es el llamado nefroma mesoblástico. Se presenta un caso que se observó recientemente en el Laboratorio de Patología del Hospital Maternidad de Lima con el objeto de incentivar el estudio de esta entidad y comentar algunos aspectos que se considera interesante discutir.

Wilms’ Tumor: Single Centre Retrospective Study from South India

Wilms' tumor is the most common malignant renal tumor in paediatric age group, and is classically managed by multimodal treatment which involves surgery, radiotherapy and chemotherapy. The last few decades have seen a dramatic change in the prognosis of this disease, which once was a uniformly lethal malignancy. While there is plenty of data in world literature on the outcome of Wilms' tumor, there is paucity of data from India. Hence, we conducted the present study to analyze the outcome of Wilms' tumor at our institute. To study the clinicopathologic profile and outcome of Wilms' tumor with NWTS (National Wilms' Tumor Study Group) IV protocol. Sixty-one patients with histopathological proven diagnosis of Wilms' tumor and had received treatment at our institute from Jan 2003 through Dec 2010 were included for analysis. Patients received treatment based on NWTS IV protocol. Patients were analysed for overall survival and event free survival and these outcomes were correlated with age, sex, stage at presentation and histology. Favourable histology which included focal anaplasia was found in 80.3% while unfavourable histology was elicited in 19.7% of the cases. The estimated 5year event-free survival was 83.3% and overall survival was 85.2%. Tumour histology was the single most important factor predicting the survival. Patients with childhood Wilms' still present very late in our setting, this poses management challenges as large tumor are technically difficult to deliver at surgery. Histology has a crucial role in outcome of this disease. With multidisciplinary approach, similar survival rates to National Wilms' Tumor Study Group seems to be achievable even in Indian scenario.

WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, Wilms tumor and cerebellar angioblastoma

The Wilms tumor 1 (WT1) gene is currently in focus by pediatric nephrologists as its mutations are associated with nephrotic syndrome, especially as part of complex clinical entities like Denys-Drash or Frasier syndrome. Renal failure may also develop in young WAGR patients, whose condition is attributed to a deletion at chromosomal region 11p13. However, only limited data exist on WT1 microdeletions. A 30-year-old male patient, with a history of genital malformations, a Wilms tumor manifested during the treatment of acute lymphoid leukemia (ALL) at the age of 4, and a cerebellar angioblastoma, was referred with proteinuria and a reduced glomerular filtration rate (GFR). Kidney biopsy revealed FSGS. Although all WT1 exons were amplified with polymerase chain reaction (PCR) and sequenced, none of them showed a mutation. However, an formalin-fixed, paraffin- embedded (FFPE) tissue sample of the patient's childhood Wilms tumor showed WT1- positivity restricted to the renal tumor cells, so the WT1 gene was investigated further. Using quantitative reverse transcription PCR (qRT-PCR), the gene was found to be present in only one copy in the patient's genomic DNA sample, while both copies were detected in both parents. In the patient's sister, the proximal region of WT1 was shown to have an extra copy. Evidence suggests that a heterozygous microdeletion of the gene WT1 is responsible for the patient's disease. It seems reasonable to assume a possible abnormality affecting meiotic crossing over at the WT1 locus in one of the parents.

Adult Wilms’ tumor – diagnosis and current therapy

IntroductionWilms’ tumour is one of the commonest malignant tumours of childhood. It appears mainly in the first 5 years of life. Incidental examples of nephroblastoma in adults have been described in literature (about 3% of all described cases). There are diagnostic and therapeutic difficulties in that older age group. The preoperative diagnosis of nephroblastoma in adults is difficult because there are no specific radiographic findings that allow to distinguished it from the more common adult renal tumors. Histopathologically, there is no difference between adult and childhood Wilms’ tumor.Materials and methodsThe PubMed database and current literature search was conducted for reports on clinical and histopathological features of nephroblastoma in adults. We also reviewed the literature in terms of treatment strategy, toxicity and prognostic factors.ResultsUp till now, several biological factors have been identified that may be in future new prognostic factors. Modern treatment regiments improved OS in this group of patients (OS rates of 90%). The prognosis remain still worse for about 25% of patients with anaplastic, bilateral and recurrent disease.ConclusionsDue to the fact that nephroblastoma is a very rare type of cancer, adult patients should be treated in an individual way based on the available schemes used in children. Toxicity in adults is higher than in children.

Defects in the DNA Mismatch Repair System Do Not Contribute to the Development of Childhood Wilms Tumors

Wilms tumor is the most common childhood renal malignancy. Most Wilms tumors occur sporadically, whereas a genetic predisposition is described in 9-19% of the Wilms tumor patients. In addition to constitutional aberrations, somatic aberrations in multiple genetic loci such as WT1, WT2 or locus 11p15.5, CTNNB1, WTX, TP53, FBXW7, and MYCN have also been linked to Wilms tumorigenesis. In sporadic Wilms tumors, however, the driving somatic genetic aberrations need to be further unraveled. Therefore, it is necessary to obtain more insight into other underlying mechanisms. Little is known about the role of defects in the DNA mismatch repair system in the etiology of Wilms tumors. To detect mismatch repair deficiency in a full cohort of Wilms tumor patients, we combined immunohistochemistry for the expression of mismatch repair proteins and microsatellite instability (MSI) analysis by a fluorescent multiplex polymerase chain reaction-based assay. Of the 121 Wilms tumor patients treated between 1987 and 2010 in our institution, 100 samples from 97 patients were available for analysis. Nuclear staining for MLH1, MSH2, MSH6, and PMS2 proteins was present in all 100 Wilms tumor samples. No pattern of MSI was found in any of the 100 investigated Wilms tumor samples. The matching results of normal expression of the mismatch repair proteins detected by immunohistochemistry and the absence of MSI by DNA analysis in 100 Wilms tumor samples lead us to conclude that defects in the DNA mismatch repair system do not play a significant role in the development of Wilms tumors.

Defects in the DNA mismatch repair system do not contribute to the development of childhood Wilms tumors

Defects in the DNA mismatch repair system do not contribute to the development of childhood Wilms tumors

Fatal Ischemic Enteritis with Hemorrhage—A Late Complication of Treated Wilms Tumor

A 35-year-old man with a history of childhood Wilms tumor successfully treated with radiotherapy, chemotherapy, and surgery, collapsed and died unexpectedly in hospital following admission for abdominal pain. At autopsy, there was ischemic necrosis of the small intestine with altered blood within the stomach and small intestine. Within the upper abdominal aorta, there was patchy confluent calcific atherosclerosis with extension into the proximal superior mesenteric artery which was occluded by thrombus. Death was attributed to ischemic enteritis of the small intestine caused by mesenteric artery thrombosis complicated by gastrointestinal hemorrhage with aspiration. Localization of atherosclerosis to the radiation field with no significant atherosclerosis elsewhere and the young age of the decedent were supportive of radiation-induced atherogenesis. Geographically, localized atherosclerosis at autopsy in a tumor survivor should raise the possibility of a treatment-related side effect that may directly contribute to death many years after the original therapeutic intervention.

Reply By Authors

No AccessJournal of UrologyOncology and Transplant1 Oct 2012Reply by Authors View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2591AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 188(4S), pp. 1498–1499 References 1 : Twenty-five year follow-up of childhood Wilms tumor: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer2011; 57: 1210. Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 188Issue 4SOctober 2012Page: 1498-1499 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

Frequency of WT1 and 11p15 constitutional aberrations and phenotypic correlation in childhood Wilms tumour patients

IntroductionIn 9–17% of Wilms tumour patients a predisposing syndrome is present, in particular WT1-associated syndromes and overgrowth syndromes. Constitutional WT1 mutations or epigenetic changes on chromosome 11p15 have also been described in Wilms tumour patients without phenotypic abnormalities. Thus, the absence of phenotypic abnormalities does not exclude the presence of a genetic predisposition, suggesting that more Wilms tumour patients may have a constitutional abnormality. Therefore, we investigated the frequency of constitutional aberrations in combination with phenotype. Patients & methodsClinical genetic assessment, as well as molecular analysis of WT1 and locus 11p15 was offered to a single-centre cohort of 109 childhood Wilms tumour patients. ResultsTwelve patients (11%) had a WT1 aberration and eight patients (8%) had an 11p15 aberration. Of the 12 patients with a WT1 aberration, four had WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations and mental retardation), one had Denys-Drash syndrome, four had genitourinary anomalies without other syndromic features and three had bilateral disease with stromal-predominant histology at young age without congenital anomalies. Of the eight patients with an 11p15 aberration, four had Beckwith–Wiedemann syndrome (BWS), two had minor features of BWS and two had no stigmata of BWS or hemihypertrophy. ConclusionConstitutional WT1 or 11p15 aberrations are frequent in Wilms tumour patients and careful clinical assessment can identify the majority of these patients. Therefore, we would recommend offering clinical genetic counselling to all Wilms tumour patients, as well as molecular analysis to patients with clinical signs of a syndrome or with features that may indicate a constitutional WT1 or 11p15 aberration.

Development of Breast Cancer in a 21-Year-Old Childhood Wilms' Tumor Survivor With a BRCA1 2634delC Mutation

Breast cancer at age 21 is rare, even in individuals who have a genetic predisposition. These early diagnoses are usually the result of a hereditary cancer syndrome. Other contributing factors, such as chemotherapy and radiation for previous malignancies, can also increase the risk of secondary malignancies, including breast cancer. Here we present one of the youngest cases of breast cancer reported in the literature: a 21-year-old Wilms' tumor survivor (diagnosed at age 6), who was found to have a familial BRCA1 mutation and was diagnosed with ductal carcinoma in situ at age 21.

Twenty‐five year follow‐up of childhood Wilms tumor: A report from the Childhood Cancer Survivor Study

Treatment cures over 90% of children with Wilms tumor (WT) who subsequently risk late morbidity and mortality. This study describes the 25-year outcomes of 5-year WT survivors in the Childhood Cancer Survivor Study (CCSS). The CCSS, a multi-institutional retrospective cohort study, assessed WT survivors (N = 1,256), diagnosed 1970-1986, for chronic health conditions, health status, health care utilization, socioeconomic status, subsequent malignant neoplasms (SMNs), and mortality compared to the US population and a sibling cohort (N = 4,023). The cumulative incidence of all and severe chronic health conditions was 65.4% and 24.2% at 25 years. Hazard ratios (HR) were 2.0, 95% confidence interval (CI) 1.8-2.3 for grades 1-4 and 4.7, 95%CI 3.6-6.1 for grades 3 and 4, compared to sibling group. WT survivors reported more adverse general health status than the sibling group (prevalence ratio [PR] 1.7; 95%CI 1.2-2.4), but mental health status, socioeconomic outcome, and health care utilization were similar. The cumulative incidence of SMN was 3.0% (95%CI 1.9-4.0%) and of mortality was 6.1% (95%CI 4.7-7.4%). Radiation exposure increased the likelihood of congestive heart failure (CHF) (no doxorubicin-HR 6.6; 95%CI 1.6-28.3; doxorubicin ≤ 250 mg/m(2) -HR 13.0; 95%CI 1.9-89.7; doxorubicin >250 mg/m(2) -HR 18.3; 95%CI 3.8-88.2), SMN (standardized incidence ratio [SIR] 9.0; 95%CI 3.9-17.7 with and 4.9; 95%CI 1.8-10.6 without doxorubicin) and death. Long-term survivors of WT treated from 1970 to 1986 are at increased risk of treatment related morbidity and mortality 25 years from diagnosis.

P16 and p27 tumor suppressor gene methylation status in childhood Wilms tumor cases

To analyze the methylation status of the promoter regions of p16 and p27 genes in Wilms tumor patients. These tumor suppressor genes are associated with 2 main pathways regulating the G1/S transition of the cell cycle. Materials and methods: Sixteen patients with Wilms tumor were included in the study. The methylation status of CpG islands in the p16 and p27 genes was analyzed by the polymerase chain reaction (PCR) technique in the tumor tissue samples obtained from all patients. Five tissue samples of normal kidney were obtained from pathology department archives. Results: P16 gene promoter methylation was detected in 2 of 16 (12.5%) patients, one of which was heterozygous and the other homozygous. P27 gene promoter methylation was also found in 2 of 16 (12.5%) patients, one of which was heterozygous and the other homozygous. No methylation status was observed in normal kidney tissues. Conclusion: Our results showed that the incidence of CpG island promoter region methylation of the p16 and p27 tumor suppressor genes in Wilms tumor was low. However, larger series are needed to determine the prognostic value of DNA methylation of p16 and p27 in Wilms tumor patients.

TREATMENT OF WILMS TUMOR: A Report from the Turkish Pediatric Oncology Group (TPOG)

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. Methods and patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III–IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II–IV UH tumors, VCR + Act-D + ADR + etoposide + RT. Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases ≤2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.