Peer-reviewed article
Childhood cancer predisposition study: a prospective registry and biorepository protocol.
Perrino MR, MacFarland SP, Maese L, Vagher J, Kamihara J et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a protocol for the Childhood Cancer Predisposition Study, a multi-centre registry and biorepository for children aged 0-21 years with cancer predisposition syndromes. The study aims to understand how genetic factors influence cancer risk in children and whether following recommended surveillance guidelines leads to earlier cancer detection and better survival. Researchers will collect genetic samples, medical history, and family cancer information from around 1,050 children and their family members.
Key points
- More than 15% of children diagnosed with cancer carry a germline pathogenic variant in a cancer predisposition gene
- Over 100 genes are associated with cancer predisposition syndromes, but each is individually rare
- Current clinical care recommendations are based on expert consensus with a 'one size fits all' approach
- The study will investigate whether adherence to tumour surveillance guidelines is associated with earlier tumour detection and improved survival
- The study will identify barriers that prevent adherence to surveillance guidelines
Limitations
This is a protocol document describing a prospective study design rather than reporting results, so it cannot tell us what outcomes were observed or whether the interventions were effective. The study is still in early stages of enrolment and has not yet generated data on the primary research questions.
Abstract
Introduction Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is diagnosed, current recommendations for clinical care are based primarily on expert consensus with a 'one size fits all' approach to management. Detailed knowledge of genotype-phenotype associations and the impact of genetic modifiers is lacking, and due to strong ascertainment bias of children already diagnosed with cancer predominantly being tested for a CPS, the true cancer risk is likely overestimated. Methods and analyses The Childhood Cancer Predisposition Study (CCPS) is a multi-centre registry and biorepository for children and adolescents aged 0-21 years with a clinical or molecularly confirmed CPS and their family members (NCT04511806). The study objectives are to characterise the natural history of each CPS, correlate the natural history phenotype with CPS genotype, evaluate the efficacy of standard surveillance strategies and allow future investigation into the feasibility and effectiveness of novel surveillance strategies. The principal study question is whether adherence to recommended tumour surveillance guidelines is associated with earlier detection of tumours and/or improved survival. We will also address what barriers exist that prevent adherence to surveillance guidelines. Data collected from primary subjects includes detail about the CPS, genomic data, cancer history and family cancer history, as well as information about tumour surveillance. Required biospecimen collection includes germline DNA samples, with optional collection of serial blood and stool samples. Planned enrolment is 1050 primary subjects. Ethics and dissemination CCPS was reviewed and approved by a central IRB (WCG IRB 2020P002450) and the Research Ethics Board at The Hospital for Sick Children in Toronto (1000072286). Written informed consent is obtained from all participants. Data and specimens are available to qualified investigators by request to address specific research questions through a standardised research application process. In addition, de-identified data are available through the Pediatric Cancer Data Commons for exploration. Analysed data will be disseminated in peer-reviewed publications and at conferences including meetings inclusive of patient and family advocacy groups. Trial registration number NCT04511806.