Parents’ expectations, preferences, and recall of germline findings in a childhood cancer precision medicine trial

Abstract

BackgroundGermline genome sequencing in childhood cancer precision medicine trials may reveal pathogenic or likely pathogenic variants in cancer predisposition genes in more than 10% of children. These findings can have implications for diagnosis, treatment, and the child’s and family’s future cancer risk. Understanding parents’ perspectives of germline genome sequencing is critical to successful clinical implementation.MethodsA total of 182 parents of 144 children (<18 years of age) with poor‐prognosis cancers enrolled in the Precision Medicine for Children with Cancer trial completed a questionnaire at enrollment and after the return of their child’s results, including clinically relevant germline findings (received by 13% of parents). Parents’ expectations of germline genome sequencing, return of results preferences, and recall of results received were assessed. Forty‐five parents (of 43 children) were interviewed in depth.ResultsAt trial enrollment, most parents (63%) believed it was at least “somewhat likely” that their child would receive a clinically relevant germline finding. Almost all expressed a preference to receive a broad range of germline genomic findings, including variants of uncertain significance (88%). Some (29%) inaccurately recalled receiving a clinically relevant germline finding. Qualitatively, parents expressed confusion and uncertainty after the return of their child’s genome sequencing results by their child’s clinician.ConclusionsMany parents of children with poor‐prognosis childhood cancer enrolled in a precision medicine trial expect their child may have an underlying cancer predisposition syndrome. They wish to receive a wide scope of information from germline genome sequencing but may feel confused by the reporting of trial results.

Insights into parent and adolescent patient understanding of genomic sequencing

“…McGill et al 5 . found that parents are interested in the disclosure of VUSs, consistent with other recent studies 21 .…”

“…Postdisclosure counseling should also include education about cascade testing for family members (when appropriate), syndrome and patient support/ advocacy groups, and outlining plans for surveillance and cancer risk reduction. Importantly, McGill et al 5 also found that a third of parents of children with negative germline results misperceived that their child had clinically relevant germline findings, which supports informational needs for those with negative results as well. 14 Such misperceptions risk unnecessary distress and/or anxiety regarding future cancer risk, surveillance and medical follow-up, and genetic testing for family members.…”

“…McGill et al 5 . separately report parent expectations for their child’s PRISM germline findings and recall of actual germline results.…”

“…In this issue of Cancer, Gereis et al 4 and McGill et al 5 prospectively examine parent and adolescent patient understanding and expectations of paired tumor-germline sequencing from consent through to germline results via a mixed-methods design as part of the PRecISion Medicine for Children with Cancer trial (PRISM; a precision medicine trial assessing the feasibility and utility of somatic and germline sequencing for children with poor prognosis malignancies).…”

“…Posttest genetic counseling should not only disclose results but also address parental understanding of results, psychosocial considerations, and implications for the patient and close relatives. 14 Although parents of children with clinically relevant results in PRISM were generally accurate in their recall, a subset were unsure about the results, 5 which indicates the importance of better educating some families of children with pathogenic germline results. Postdisclosure counseling should also include education about cascade testing for family members (when appropriate), syndrome and patient support/ advocacy groups, and outlining plans for surveillance and cancer risk reduction.…”