Justine Naomi van der Beek

Wilms tumor (WT) is the most common pediatric renal tumor, and with multidisciplinary treatment overall outcomes are excellent. However, a small subset of patients with WT will relapse. The ideal treatment of relapsed WT is yet to be defined. Ongoing studies through the Children's Oncology Group Renal Tumors Committee (COG‐RTC) and the International Society of Paediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) aim to improve risk stratification and treatment strategies. Members met at the SIOP 55th Annual Congress 2023 to outline available data and knowledge gaps and develop future research priorities.

Objectives: The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) discourages invasive procedures to determine the histology of paediatric renal neoplasms at diagnosis. Therefore, the histological subtype of Wilms’ tumours (WT) is unknown at the start of neoadjuvant chemotherapy. MR-DWI shows potential value as a non-invasive biomarker through apparent diffusion coefficients (ADCs). This study aimed to describe MR characteristics and ADC values of paediatric renal tumours to differentiate subtypes. Materials and methods: Children with a renal tumour undergoing surgery within the SIOP-RTSG 2016-UMBRELLA protocol were prospectively included between May 2021 and 2023. In the case of a total nephrectomy, a patient-specific cutting guide based on the neoadjuvant MR was 3D-printed, allowing a correlation between imaging and histopathology. Whole-tumour volumes and ADC values were statistically compared with the Mann-Whitney U-test. Direct correlation on the microscopic slide level was analysed through mixed model analysis. Results: Fifty-nine lesions of 54 patients (58% male, median age 3.0 years (range 0–17.7 years)) were included. Forty-four lesions involved a WT. Stromal type WT showed the lowest median decrease in volume after neoadjuvant chemotherapy (48.1 cm³, range 561.5–(+)332.7 cm³, p = 0.035). On a microscopic slide level (n = 240 slides) after direct correlation through the cutting guide, stromal areas showed a significantly higher median ADC value compared to epithelial and blastemal foci (p < 0.001). With a cut-off value of 1.195 * 10⁻³ mm²/s, sensitivity, and specificity were 95.2% (95% confidence interval 87.6–98.4%) and 90.5% (95% confidence interval 68.2–98.3%), respectively. Conclusion: Correlation between histopathology and MR-DWI through a patient-specific 3D-printed cutting guide resulted in significant discrimination of stromal type WT from epithelial and blastemal subtypes. Clinical relevance statement: Stromal Wilms’ tumours could be discriminated from epithelial- and blastemal lesions based on high apparent diffusion coefficient values and limited decrease in volume after neoadjuvant chemotherapy. This may aid in future decision-making, especially concerning discrimination between low- and high-risk neoplasms. Key Points: MR-DWI shows potential value as a non-invasive biomarker in paediatric renal tumours. The patient-specific cutting guide leads to a correlation between apparent diffusion coefficient values and Wilms’ tumour subtype. Stromal areas could be discriminated from epithelial and blastemal foci in Wilms’ tumours based on apparent diffusion coefficient values.

Background: Congenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients 3, respectively, versus 41.0 cm³ for the classic type (P−3 mm²/s. Conclusion: This retrospective international collaborative study showed classic type congenital mesoblastic nephroma predominantly presented as a homogeneous T2-weighted isointense mass with a typical concentric ring sign, whereas the cellular type appeared more heterogeneous. Future studies may use identified MRI characteristic of congenital mesoblastic nephroma for validation and for exploring the discriminative non-invasive value of MRI, especially from Wilms tumor. Graphical

Introduction: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology–Renal Tumor Study Group (SIOP‐RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC.Methods: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti‐programmed cell death 1 (PD‐(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced‐stage and relapsed pediatric RCC.Results: Of the 31 identified patients (0–18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT‐RCC) (21/31) and the remaining patients mainly presented with papillary or clear‐cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono‐ or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis.Conclusion: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Pediatric renal cell carcinoma (RCC) is a rare malignancy. Magnetic resonance imaging (MRI) is the preferred imaging modality for assessment of these tumors. The previous literature has suggested that cross-sectional-imaging findings differ between RCC and other pediatric renal tumors and between RCC subtypes. However, studies focusing on MRI characteristics are limited. Therefore, this study aims to identify MRI characteristics of pediatric and young-adult RCC, through a single-center case series and literature review. Six identified diagnostic MRI scans were retrospectively assessed, and an extensive literature review was conducted. The included patients had a median age of 12 years (63–193 months). Among other subtypes, 2/6 (33%) were translocation-type RCC (MiT-RCC) and 2/6 (33%) were clear-cell RCC. Median tumor volume was 393 cm³ (29–2191 cm³). Five tumors had a hypo-intense appearance on T2-weighted imaging, whereas 4/6 were iso-intense on T1-weighted imaging. Four/six tumors showed well-defined margins. The median apparent diffusion coefficient (ADC) values ranged from 0.70 to 1.20 × 10⁻³ mm²/s. In thirteen identified articles focusing on MRI characteristics of MiT-RCC, the majority of the patients also showed T2-weighted hypo-intensity. T1-weighted hyper-intensity, irregular growth pattern and limited diffusion–restriction were also often described. Discrimination of RCC subtypes and differentiation from other pediatric renal tumors based on MRI remains difficult. Nevertheless, T2-weighted hypo-intensity of the tumor seems a potential distinctive characteristic.

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow‐up of these patients. Initial workup for staging is mainly performed by cross‐sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology ‐ Renal Tumor Study Group (SIOP‐RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP‐RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international groups, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus‐based imaging guidelines for the initial evaluation of a child with suspected WT and follow‐up during and after therapy co‐developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.

Background: Pediatric renal tumors are often heterogeneous lesions with variable regions of distinct histopathology. Direct comparison between in vivo imaging and ex vivo histopathology might be useful for identification of discriminating imaging features. Objective: This feasibility study explored the use of a patient-specific three-dimensional (3D)-printed cutting guide to ensure correct alignment (orientation and slice thickness) between magnetic resonance imaging (MRI) and histopathology. Materials and methods: Before total nephrectomy, a patient-specific cutting guide based on each patient’s preoperative renal MRI was generated and 3-D printed, to enable consistent transverse orientation of the histological specimen slices with MRI slices. This was expected to result in macroscopic slices of 5 mm each. The feasibility of the technique was determined qualitatively, through questionnaires administered to involved experts, and quantitatively, based on structured measurements including overlap calculation using the dice similarity coefficient. Results: The cutting guide was used in eight Wilms tumor patients receiving a total nephrectomy, after preoperative chemotherapy. The median age at diagnosis was 50 months (range: 4–100 months). The positioning and slicing of the specimens were rated overall as easy and the median macroscopic slice thickness of each specimen ranged from 5 to 6 mm. Tumor consistency strongly influenced the practical application of the cutting guide. Digital correlation of a total of 32 slices resulted in a median dice similarity coefficient of 0.912 (range: 0.530–0.960). Conclusion: We report the feasibility of a patient-specific 3-D-printed MRI-based cutting guide for pediatric renal tumors, allowing improvement of the correlation of MRI and histopathology in future studies.

Background: The SIOP‐Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis‐based treatment initiation, but only for a relatively small percentage of approximately 10% of non‐Wilms tumors (non‐WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics.Purpose: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors.Study Type: Consensus process using a Delphi method.Population: Not applicable.Field Strength/Sequence: Abdominal MRI including T1‐ and T2‐weighted imaging, contrast‐enhanced MRI, and diffusion‐weighted imaging at 1.5 or 3 T.Assessment: Twenty‐three radiologists from the SIOP‐RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5‐point Likert scales, ranking‐ and multiple choice questions.Statistical Tests: The cut‐off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale.Results: Consensus on specific characteristics mainly concerned the discrimination between WTs and non‐WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors.Data Conclusion: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts.Level of Evidence: 3Technical Efficacy Stage: 3