Cancer Predisposition Testing by Family-based Whole-genome Sequencing (WGS) in Every Child With Newly Diagnosed Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Family-based whole genome sequencing.
- Who it may be relevant to
- Registry conditions: Neoplastic Syndromes, Hereditary, Cancer, Genetic Predisposition to Disease. Basic parameters: up to 21 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Assessment of the Utility of Family-based (Trio) Whole-genome Sequencing for Cancer Predisposition Testing in Sequential Newly Diagnosed Paediatric and Adolescent Cancer Patients
Overview
Assessment of the utility of family-based (trio) whole-genome sequencing for cancer predisposition testing in sequential newly diagnosed paediatric and adolescent cancer patients
Detailed description
Cancer Predisposition Syndromes (CPS), caused by germline mutations in cancer predisposition genes (CPG) are heritable disorders associated with an increased risk of developing certain types of cancer.
Knowledge of CPG will advance the understanding of tumorigenesis, improve patient care, and facilitate genetic counselling of patients and families. But the prevalence of CPS in Australian children with cancer and the psychosocial impact of germline sequencing to identify CPG have not been studied.
The clinical benefit of family-based WGS in every new child with cancer compared with conventional predictive factors is currently unknown. By testing every child with newly diagnosed cancer the aim is to determine the utility of this approach and its impact on participants and families.
The principal objective of the proposed multicentre prospective study is establish the clinical benefit and utility of family-based WGS to identify underlying CPS in every newly diagnosed child with cancer.
Interventions
- Diagnostic test Family-based whole genome sequencing
1. Germline whole-genome family-based sequencing and variant identification. 2. Multidisciplinary Meeting case discussion. 3. Recommendation of referral to a Cancer Genetics Clinic for further investigation, follow up and/or genetic counselling. 4. Psychosocial study to analyse the impact of germline sequencing on families.
Primary outcome measures
- The proportion of patients with CPS identify by WGS as compared to those correctly identified by clinical information (i.e. family history, tumour type, physical findings). [Time frame: 2 years]
Secondary outcome measures (11)
- The proportion of individuals found to have a reportable germline mutation in a CPG [Time frame: 2 years]
- The proportion of patients who have de-novo vs. inherited mutation in CPG. [Time frame: 2 years]
- Turnaround time for issuing a report to the treating clinician. [Time frame: 2 years]
- The proportion of participants with a complete recording of family history of cancer. [Time frame: 2 years]
- Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors. [Time frame: 2 years]
- The proportion of participants with CPS who undergo cancer surveillance. [Time frame: 2 years]
- Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence. [Time frame: 2 years]
- Quantify the frequency of rare noncoding, complex, and oligogenic variation (in units of variants/person, and genes with variants/person), as detected by WGS, in a paediatric cancer population relative to cancer-free parents and population controls. [Time frame: 2 years]
- Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer. [Time frame: 2 years]
- The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents. [Time frame: 5 years]
- Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer. [Time frame: 5 years]
Eligibility criteria
- New diagnosis of malignancy
- Age ≤ 21 years
- Written informed consent
Psychosocial component:
- Participants (≥ 12 years)
- Parent/caregiver(s) of participants
- Healthcare professionals involved in the care of patients enrolled in the study
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Australia · 3 centers
- John Hunter Children's Hospital — Newcastle
- Sydney Children's Hospital — Sydney
- The Children's Hospital at Westmead — Sydney
Publications
- Fuentes Bolanos NA, Padhye B, Daley M, Hunter J, Hetherington K, Warby M, Courtney E, Kirk J, Josephi-Taylor S, Chen Y, Alvaro F, Barlow-Stewart K, Wong-Erasmus M, Barahona P, Ajuyah P, Altekoester AK, Tyrrell VJ, Lau LMS, Wakefield C, Sylvester D, Tucker K, Pinese M, Dalla Pozza L, O'Brien TA. Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlyi PMID 37253493
Identifiers
NCT: NCT04903782 · PREDICT