Arnauld C. Verschuur

Background: Congenital mesoblastic nephroma (CMN) is the most common renal neoplasm diagnosed in the very first months of life. Complete nephrectomy only is the gold standard treatment. Objectives and methods: This retrospective study aimed to explore the characteristics and outcome of CMN patients registered in the SIOP 93–01, SIOP WT 2001, UK-IMPORT, and AIEOP studies (1993–2019). Results: A total of 376 CMN cases were identified, with a median age at diagnosis of 28 days. Stage information was available for 337 patients: 92/337 (27.4%) were diagnosed with stage I, 177/337 (52.6%) with stage II, and 67/337 (20%) with stage III. Among 272 patients with available histological data, 113/272 (41.5%) had classic, 105/272 (38.6%) cellular, and 54/272 (19.9%) mixed subtype. Treatment details were available for 314 patients; 248 (79%) underwent initial surgery, and 66 (21%) received preoperative chemotherapy. Among the latter group, 60% of patients showed a measurable reduction in tumor volume, indicating a favorable response to chemotherapy. The 5-year event-free survival rate was 93.8%, and the overall survival rate was 96.9%. The cumulative 5-year incidence of relapse was 5.3%, with a median time to recurrence of 4 months. Of the 16 relapse cases, 8 were in the cellular subtype, 5 in the mixed subtype, and 3 in the classical subtype. Conclusions: This study confirms that CMN patients have an excellent outcome, with complete surgical resection being curative in the majority of cases. Chemosensitivity is observed in a significant proportion, suggesting that neoadjuvant chemotherapy may be a viable option in selected cases. While age at diagnosis, histological subtype, and survival outcomes are consistent with previous reports, we highlight that recurrences, though infrequent, tend to occur early and are not restricted to the cellular subtype. Further prospective studies and molecular investigations are required to refine clinical management strategies and update treatment recommendations.

PURPOSE: Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers. MATERIALS AND METHODS: A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants ( TP53 [and/or 17p loss], MYCN , FBXW7 , WT1 , WTX , SIX1/SIX2 , DROSHA , DGCR8 , AMER1 , CTNNB1 , GPC3 , MLLT1 , DICER1 , DIS3L2 ). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool. RESULTS: Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance. TP53 and MYCN were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants. CONCLUSION: 1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of TP53 , MYCN , and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.

BACKGROUND AND SCOPE: Historical data sources for rare cancers are valuable for data-driven research. The International Society of Pediatric Oncology Renal Tumors Study Group (SIOP-RTSG) has been conducting clinical research on pediatric renal tumors for more than 50 years. Since 1993, data have been collected across multiple countries, using standardized paper-based case report forms that were digitally transcribed into electronic databases. Until 2019, prospectively collected data are present in nine different electronic sources from three consecutive clinical studies. More than 10,000 patient cases of kidney cancer in children are registered in totality. However, the necessary merging of numerous sources to answer a research question is repetitive, time consuming, and unsustainable in the long term. SOLUTION: By mapping and formatting the structure of these nine databases, a single database was created that was similar in design to the prospective study database. This allows the data from the past and current studies to be accessed and queried efficiently with standardized syntax and reports. EVALUATION: We validated this new database by reviewing whether uploads were complete and successful, mapped items were coded correctly, or discrepancy appeared in the export. Comparisons with retrospective reports were made to ensure the datasets were reproducible. RELEVANCE: Researchers have access to a large number of patients through this validated aggregated database. Data maintenance and extraction is efficient, and it offers the possibility to complete missing data directly into the central database. This ultimately ensures long-term availability in a secure, flexible, and responsible manner, in accordance with FAIR principles. HOW TO ACCESS/USE: Researchers can send questions to SIOP-RTSG and, if necessary, gain access to the database after short training. Access granted would depend on user's role.

PURPOSE: The International Society of Paediatric Oncology–Renal Tumour Study Group (SIOP-RTSG) classifies blastemal-type Wilms tumor (WT) after preoperative chemotherapy as high-risk (HRWT). It remains unresolved whether residual absolute volume of blastema (AVB) functions as an independent prognostic factor across WT subtypes. MATERIALS AND METHODS: AVB was calculated from preoperative tumor volume, necrosis percentage, and viable blastema using prospectively collected data from 3,459 patients with unilateral WT treated in the SIOP WT 2001 study between 2001 and 2018. Martingale residual plots defined AVB thresholds discriminating survival in localized HRWT, intermediate-/low-risk WT (IRWT/LRWT), and metastatic WT (stage IV). Complete AVB data were available for 1,802 patients (51.2%); 298 (16.5%) had stage IV disease. Of 1,504 patients with localized WT, 265 (17.6%) had HRWT, 1,203 (79.9%) had IRWT, and 36 (2.4%) had LRWT. RESULTS: Multivariable Cox regression adjusted for age, sex, and local stage confirmed significantly worse survival for patients exceeding these AVB thresholds: (1) IRWT (≥20 mL): Hazard ratio for event-free survival (EFS) 2.93 (95% CI, 2.08 to 4.12) and overall survival (OS) 2.76 (95% CI, 1.32 to 5.77); (2) HRWT (≥100 mL): EFS 2.89 (95% CI, 1.59 to 5.26) and OS 3.25 (95% CI, 1.45 to 7.27); and (3) stage IV (≥10 mL): EFS 5.78 (95% CI, 3.65 to 9.17) and OS 4.59 (95% CI, 2.57 to 8.17). Patients above these thresholds had significantly lower 2-year EFS ( P < .0001). In stage II to III IRWT patients with AVB ≥20 mL, those treated with doxorubicin had superior EFS versus those without (87.6%, 95% CI, 81.5 to 94.1 v 69.2%, 95% CI, 59.8 to 80.1; P = .0064). CONCLUSION: AVB after preoperative chemotherapy is a strong, independent predictor of both EFS and OS in WT across risk groups. An AVB of ≥20 mL identifies a clinically relevant subset of patients with IRWT who may benefit from intensified therapy with doxorubicin. These findings support the use of AVB as a stratification criterion in future SIOP-RTSG protocols.

Paediatric kidney tumours are generally associated with a favourable survival rate. Most children are diagnosed with Wilms tumour, which has a 90% long-term survival rate with conventional front-line and salvage therapies. However, treatments and outcomes of children with relapsed non-Wilms tumours, such as malignant rhabdoid tumour of the kidney, renal-cell carcinoma (including renal medullary carcinoma), clear-cell sarcoma of the kidney, anaplastic sarcoma of the kidney and congenital mesoblastic nephroma are not well defined. Several of these non-Wilms tumours include unfavourable prognostic subtypes. Currently available data on non-Wilms tumours support advancing studies that pivot from conventional strategies towards disease-specific, biologically driven novel treatments to improve outcomes for each of these rare childhood kidney tumours.

Table of dose-limiting toxicities

Distribution of the median clearance of irinotecan and its active metabolite (SN-38) derived from the published variability distribution of the clearances versus the estimated median clearance of irinotecan and SN-38 in this study.

Distribution of individual clearance of irinotecan and its active metabolite SN-38.