Challenges and Solutions in Identifying Pediatric Cancer Predisposition Syndromes - Introducing MIPOGG

We are delighted to give the opportunity to Dr. Catherine Goudie, Dr. Noelle Cullinan and the MIPOGG team to let you know more about MIPOGG.

The diagnosis of a childhood cancer is a devastating event for families. Facing a potentially life-threatening diagnosis, affected children and their families are involuntarily thrust into a daunting world of chemotherapy, surgery, radiation therapy, immunotherapy, diagnostic and surveillance scans, disease monitoring and follow-up. One of the most frequent questions, we, as oncologists, encounter with such families, is “Why?” Increasingly, families are aware of the role of genetic disorders in the development of diseases including childhood cancers and therefore, parents commonly express concerns about the implications of a childhood cancer diagnosis to cancer risk for themselves, their other children and extended family members. It is becoming increasingly important for us, as clinicians, to address these concerns comprehensively for each family we encounter.

Cancer predisposition syndromes (CPSs) are now understood to contribute to the development of childhood cancer in approximately 10% of cases. The diagnosis of a CPS is crucial for a number of reasons. These include adapting cancer therapies relative to the underlying CPS, helping to anticipate, and sometimes prevent, future cancers in a patient (through early interventions and disease surveillance), identifying at-risk family members and enhancing our understanding of the genetic contribution to cancer development. While risk factors for an underlying CPS have been well-described for many adult cancers (e.g. breast, colorectal cancers), a lack of information regarding pediatric CPSs means that many of us struggle to understand and prioritize which of our young patients require referral for genetic evaluation for an underlying CPS.

The MIPOGG - McGill Interactive Pediatric OncoGenetic Guidelines is a free, downloadable eHealth app that assists physicians in identifying children with cancer who are at higher risk of having an underlying CPS. Developed by a clinical research team involving pediatric hemato-oncologists across all hematology/oncology subspecialty areas, clinical cancer geneticists, genetic counsellors, clinical and research trainees, together with a panel of expert reviewers, the evidence-based MIPOGG app was officially launched at SIOP 2019 in Lyon, France. MIPOGG uses tumor-specific algorithms and simple, quick-to-answer yes/no questions based on information readily available soon after a pediatric cancer diagnosis (e.g. clinical features, family history features and tumor-specific features), to guide clinicians towards a recommendation either for or against genetic referral.

Educational modules within the app provide information about CPSs, relevant genes seen in association with the selected cancer/tumor type and describe non-neoplastic features that may also be clinically relevant for physicians. Designed to be a clinical tool useful ‘on the ground’ for physicians, this app helps physicians to rationalize and prioritize referrals for genetic evaluation for a CPS. The decision to proceed with genetic testing is not addressed within the app and, therefore, allows clinical geneticists to decide whether or not to proceed with testing in each individual case, bearing in mind available resources within healthcare systems.

Preliminary data, collated via a multi-institutional study of children with cancer, has shown that the MIPOGG tool is highly sensitive in detecting the existence of an underlying CPS in children with cancer and a confirmed CPS (n=423). In this study, 99.3% of patients were correctly identified by MIPOGG as requiring a genetic referral for CPS evaluation. Early data also suggests that MIPOGG may help physicians detect a CPS earlier than physician-led testing. Future studies are aimed at extending the app to encompass cancers affecting the young adult population and evaluating the measurement properties of the tool when compared with comprehensive next-generation sequencing studies of children with cancer.

The MIPOGG application is now in use across 44 countries, demonstrated below, and has been downloaded by over 300 users, comprising physicians, genetic counsellors, nurses and scientific researchers.

The MIPOGG team would be delighted for you to get in touch with feedback, or for more information. Contact us by email: info@mipogg.com; through our website: https://mipogg.com; or via our downloadable app. We hope you find it useful.