An eHealth decision‐support tool to prioritize referral practices for genetic evaluation of patients with Wilms tumor

Abstract

Over 10% of children with Wilms tumor (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across health care settings, there is an urgent need to rationalize genetic referrals for this population. The McGill Interactive Pediatric OncoGenetic Guidelines study, a Canadian multi‐institutional initiative, aims to develop an eHealth tool to assist physicians in identifying children at elevated risk of having a CPS. As part of this project, a decisional algorithm specific to WT consisting of five tumor‐specific criteria (age <2 years, bilaterality/multifocality, stromal‐predominant histology, nephrogenic rests, and overgrowth features) and universal criteria including features of family history suspicious for CPS and congenital anomalies, was developed. Application of the algorithm generates a binary recommendation—for or against genetic referral for CPS evaluation. To evaluate the algorithm's sensitivity for CPS identification, we retrospectively applied the tool in consecutive pediatric patients (n = 180) with WT, diagnosed and/or treated at The Hospital for Sick Children (1997–2016). Odds ratios were calculated to evaluate the strengths of associations between each criterion and specific CPS subtypes. Application of the algorithm identified 100% of children with WT and a confirmed CPS (n = 27). Age <2 years, bilaterality/multifocality, and congenital anomalies were strongly associated with pathogenic variants in WT1. Presence of >1 overgrowth feature was strongly associated with Beckwith‐Wiedemann syndrome. Stromal‐predominant histology did not contribute to CPS identification. We recommend the incorporation of the WT algorithm in the routine assessment of children with WT to facilitate prioritization of genetic referrals in a sustainable manner.

TRIM28 variants and Wilms' tumour predisposition

“…To enable counselling, genetic testing, and early detection of WTs in young family members, it is important to recognize germline pathogenic TRIM28 variants in patients with WT. Depending on local infrastructure and resources, some paediatric oncology centres may offer routine genetic testing to all patients, while others select those who are clinically suspected of having a genetic predisposition syndrome [61].…”

Wilms tumour surveillance in at-risk children: Literature review and recommendations from the SIOP-Europe Host Genome Working Group and SIOP Renal Tumour Study Group

“…REST pathogenic variants were identified in familial WT pedigrees by Mahamdallie et al, in 2015 [82]. Heterozygous germline variants have currently been reported in 19 patients with WT from 14 families [82,83]. Additionally, a de novo deletion encompassing REST was recently identified in a patient with diffuse hyperplastic perilobar nephroblastomatosis [84].…”

Revisiting the Threshold for Cancer Genetics Referral in Patients With Wilms Tumor

“…Cullinan et al 15 created a referral support tool—MIPOGG (McGill Interactive Pediatric OncoGenetic Guidelines)—to help identify individuals in need of a genetics evaluation. This takes into account age at diagnosis, laterality, multifocal nature, NRs, histology, congenital anomalies, overgrowth, and family history.…”