Towards Personalized Discrimination of Pediatric Renal Tumors based on Magnetic Resonance Imaging

Abstract

Renal tumors account for 5-7% of all pediatric malignancies. The vast majority (85-90%) concerns a nephroblastoma (Wilms tumor, WT). A WT is a triphasic tumor, containing stromal, epithelial and/or blastemal components, leading to different histological subtypes. WTs may be preceded by- or occur together with nephrogenic rests (NR). Besides WTs, other, more rare non-WTs occur, such as congenital mesoblastic nephroma, rhabdoid tumor of the kidney, clear cell sarcoma of the kidney and renal cell carcinoma (RCC). The International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) advocates pre-operative chemotherapy, preferably without tumor biopsies at diagnosis, depending on clinical, radiological and biochemical criteria that could indicate a non-WT. Therefore, imaging plays an essential role in the diagnosis, staging and follow-up of pediatric renal tumor patients. Magnetic resonance imaging (MRI) is standard of care within the SIOP-RTSG. Besides its excellent soft tissue contrast, MRI allows for functional imaging tools such as diffusion weighted imaging (DWI) to measure the microscopic random movement of water molecules, represented by the apparent diffusion coefficient (ADC). The aim of this thesis was to increase knowledge on MRI- and DWI characteristics of pediatric renal tumors, by identifying qualitative and quantitative features that could lead to a better personalized tumor discrimination. Aiming for a direct correlation of histopathology and ADC-values, we analyzed and reported the feasibility of a 3D-printed patient-specific MRI-based cutting guide for pediatric renal tumors. This cutting guide was subsequently used in a national prospective study, in which we defined a highly discriminative cut-off value for stromal type WTs compared to epithelial- and potentially more aggressive blastemal type WTs. Early recognition of low- and high-risk histopathology might facilitate more personalized treatment already from diagnosis on. Concerning the discrimination of non-WTs from WT, there appeared to be a global lack of consensus concerning potentially discriminating imaging findings. Through a Delphi study, an experienced international group of experts agreed on potentially pathognomonic MRI characteristics of pediatric renal tumors. This study also facilitated an uniform data capturing method for retrospective international studies focusing on the identification of MRI characteristics at diagnosis. Subsequently, potentially specific MRI-DWI characteristics of non-WTs were identified, mainly based on tumor volume, T2-weighted imaging and ADC-values. Also, a special focus on RCC in this thesis stressed the need for prospective international registration of this rare malignant pediatric renal tumor, in order to further identify and validate discriminative MRI characteristics of different subtypes of RCC, as well as to limit heterogeneity in treatment. This thesis focused on several gaps of knowledge with regard to MRI- and DWI characteristics of pediatric renal tumor patients. We have made the initial steps towards a personalized discrimination of these tumors based on MRI. The results in this thesis pave the way for an increasing role of imaging, while also guiding future research directions, potentially leading to enhanced survival as well as reduced treatment-related toxicity in this population.