Consultation 2: Whole Genome Sequencing (WGS) in Childhood Cancers

Session Leads: Ruth Young, Naomi Cox

Following a brief introduction, members were split into breakout groups with each group tasked with looking at a specific scenario, as detailed below.

Scenario 1: You have consented to cancer WGS testing for your child. However unfortunately when the DNA was extracted in the lab, there was only enough DNA for WGS or standard of care (routine) tests.

Given the choice, which would you choose?

• Depending on how aggressive the form of cancer was, members felt it may be more prudent to go for the standard of care (routine) tests as these would hopefully get an actionable result sooner.

Would you rather wait longer for more information or have a quicker test which gave a less broad picture?

• By and large most would be very keen to get a quick result initially, rather than wait for longer in what would be a time of high anxiety, however, members also felt that this would be quite a burden to place on parents to make this decision at such a time and such a decision would not preclude wanting to have the broader-spectrum results as a follow-on as timescales allow.
• Regarding consent forms, we would need to investigate different tools for conveying information for a diverse number of people with different backgrounds such as age, education, ethnicity, etc.

Scenario 2: Where germline findings may influence the clinical management of the patient and the wider family would you be happy to consent for this testing?

• Opinion was divided between whether or not to consent , with it being acknowledged that this may lead to ethical questions which are very complex and highly situational. The use of a range of examples could be a very useful tool in advising on what is being consented to.
• Providing adequate guidance would be highly useful here and should be considered in the consent form. Those who didn’t feel they could consent felt that the consent form is currently too broad and would need to be broken down into finer details, using more examples.
• Members also felt that it would be important for a child to be able to re-consent once they are an adult to allow the data generated to continue to be used.
• If this information is to be conveyed by a clinician, in cases of family estrangement/adoption, this should include provision to not personally identify the individual. Instead, it may be better to let wider family members know that ‘there is an increased risk of this in your family’ without identifying the exact source. It was confirmed that no information would be relayed to wider family members without prior discussion with the patient/guardian. Members also felt that it needed to be clarified what level is the cut-off beyond which ‘distant relatives’ would be excluded.
• Anyone aged 16 or over can consent to their own treatment, noting that central to informed consent is concise and accurate information. This would enable early interventions which could potentially prevent more costly and dramatic interventions at a later point in time. Parents would only be able to over-ride consent in cases where there is proven lack of capacity
• It is important that appropriate support is given as testing may give more disclosures than initially foreseen, e.g. revealing paternity issues
• The issue of where that information may be shared and what happens to it after it is shared was seen by many as being a primary concern.
• With conditions associated with more aggressive variant-types (such as BRCA2), risks should be explained as early as possible to add context to the discussions. This will help to inform whether a patient would want to know this information
• Some people would favour receiving potentially bad news as early as possible in order to have as much time as possible to prevent, hinder or mitigate the worst-case scenarios. The concern surrounding this data focuses more on regarding where it is stored and who else has access to it
• Above all, members felt it was important to avoid ‘leading questions’ that might influence the decisions made by the patient

Scenario 3: Would you consent to WGS testing knowing unexpected information is more likely to be obtained through this method

• Those who initially consented felt that this information would not change their decision as it
  • Helps to better understand the condition of the child
  • If it opens the door to further support being provided if/when extra information is found
  • Genetic information gained from this testing can be shared amongst extended family members to facilitate their decision making
• Those who did not initially consent felt that they were uncertain of the benefit of this information to the patient, parents, society and future treatment development
• Members suggested a different set of consent forms for adult patients and paediatric patients.
• Suggested using term ‘additional’ instead of ‘incidental’ finding as ‘incidental’ may appear to down play the significance of the finding
• Consent forms need to be reviewed and scrutinised by appropriate lay panels prior to use

Cross-cutting themes

• Any decision must be predicated on sufficient information being provided to make an informed decision, this should include an explained timeline. In order to assure ourselves of informed consent we would need to consider the reading and comprehension capacity of the patient/parents when obtaining said informed consent. Information should be conveyed in the simplest possible terms

• Data sharing and implications for wider family members – we need to consider how this information would be shared amongst family members: would this be down to the patient or would the clinician take responsibility for this? Noted that this would need to be thoroughly discussed and documented in the consent forms. These forms would also need to clearly state that the test results may or may not have immediate benefits for the patient or the family, but they may have an impact on future developments. They should acknowledge key ethical considerations around sharing and disclosure of this data. This should consider how the genetic information can benefit the immediate family, as well as the birth family in cases of adoption.
• Further explanation would be needed regarding the benefits of WGS over more traditional screening types, such as tissue biopsies. Noted that WGS is already established in Rare Disease and WINGS services, with us looking to try and embed this into oncology, starting with paediatrics. It was explained that WGS removes the need for the more invasive traditional approaches to testing/screening using tissue biopsies.