Background: Paediatric precision oncology aims to match therapeutic agents to driver gene targets. We investigated whether parents and patients regret participation in precision medicine trials, particularly when their hopes are unfulfilled.Methods: Parents and adolescent patients completed questionnaires at trial enrolment (T0) and after receiving results (T1). Parents opted-in to an interview at T1. Bereaved parents completed a questionnaire 6-months post-bereavement (T1B). We analysed quantitative data with R and qualitative data thematically with NVivo, before integrating all data for interpretation.Results: 182 parents and 23 patients completed T0; 108/182 parents and 8/23 patients completed T1; 27/98 bereaved parents completed T1B; and 45/108 parents were interviewed. At enrolment, participants held concurrent hopes that precision medicine would benefit future children and their child. Participants expressed concern regarding wait-times for receipt of results. Most participants found the trial beneficial and not burdensome, including bereaved parents. Participants reported high trial satisfaction (median scores: parents: 93/100; patients: 80/100). Participants expressed few regrets (parent median scores: parents: 10/100; bereaved parents: 15/100; patient regret: 2/8 expressed minimal regret).Conclusions: Even when trial outcomes did not match their hopes, parents and patients rarely regretted participating in a childhood cancer precision medicine trial. These data are critical for integrating participants’ views into future precision medicine delivery.

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; ‘faulty gene,’ ‘altered gene,’ ‘gene change,’ and ‘genetic variant,’ analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred ‘gene change,’ ‘altered gene,’ or ‘genetic variant’ (n = 8/25). Parents least preferred ‘faulty gene’ (n = 18/25). Half the genetics professionals most preferred ‘faulty gene’ (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred ‘genetic variant’ (n = 11/29) and least preferred ‘faulty gene’ (n = 19/29). Participants across all groups perceived ‘faulty gene’ as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families’ preferred terminology, while providing accurate explanations regarding implications of genetic findings.

Introduction: Identifying an underlying germline cancer predisposition (CP) in a child with cancer has potentially significant implications for both the child and biological relatives. Cohort studies indicate that 10%–15% of paediatric cancer patients carry germline pathogenic or likely pathogenic variants in cancer predisposition genes, but many of these patients do not meet current clinical criteria for genetic testing. This suggests broad tumour agnostic germline testing may benefit paediatric cancer patients. However, the utility and psychosocial impact of this approach remain unknown. We hypothesise that an approach involving trio whole-genome germline sequencing (trio WGS) will identify children and families with an underlying CP in a timely fashion, that the trio design will streamline cancer risk counselling to at-risk relatives if CP was inherited, and that trio testing will not have a negative psychosocial impact on families. Method and analysis: To test this, we present the Cancer PREDisposition In Childhood by Trio sequencing study (PREDICT). This study will assess the clinical utility of trio WGS to identify CP in unselected patients with cancer 21 years or younger in New South Wales, Australia. PREDICT will perform analysis of biological parents to determine heritability and will examine the psychosocial impact of this trio sequencing approach. PREDICT also includes a broad genomics research programme to identify new candidate genes associated with childhood cancer risk. Ethics and dissemination: By evaluating the feasibility, utility and psychosocial impact of trio WGS to identify CP in paediatric cancer, PREDICT will inform how such comprehensive testing can be incorporated into a standard of care at diagnosis for all childhood cancer patients. Trial registration number: NCT04903782 .

Background: Germline genomic sequencing (GS) is increasingly offered to children with cancer. To optimize integration into routine care, assessment of implementation barriers and a better understanding of healthcare professionals' perspectives and experiences are needed.Methods: Healthcare professionals delivered trio germline GS to newly diagnosed pediatric and adolescent patients with cancer via the PREDICT completed questionnaires with qualitative and quantitative items. Each study site recorded reasons for eligible families' nonenrolment in PREDICT to identify barriers to recruitment. Quantitative data were analyzed via descriptive statistics, whereas qualitative data underwent inductive content analysis, with results integrated for interpretation.Results: Thirty‐three healthcare professionals participated, including 23 oncology professionals and 10 genetic professionals. Healthcare professionals perceived PREDICT as beneficial to participating and future families, and that perceptions of personal benefit and altruism were drivers of family uptake. Concerns included workforce capacity and potential family distress given the trio design and high‐stress diagnosis setting. Barriers to recruitment related to clinical decision‐making, family factors, and logistics. Although most rated their genetics/genomics knowledge as “good,” regarding germline results, few were “very confident” interpreting (29%), explaining (32%), making treatment recommendations (9.7%), and providing psychosocial support to families (29%). They acknowledged a need for further training in these areas for trainees; yet, fewer were interested in training for themselves.Conclusion: Successful implementation of routine germline GS will require targeted strategies to address logistical issues and alleviate potential negative psychosocial impacts for families. Recognizing the escalating demand on genetics experts, upskilling of the current workforce and involvement of a broader spectrum of healthcare professionals are warranted.