1. GTAB/MTB working and terms of reference
Angela George

2. GTAB/MTB working and terms of reference
Angela George

3. Where to start? Where are we aiming?
GTAB/MTB
Where to start? Where are we aiming?
Ultimately, aiming for integration of genomic findings into MDT
Routine testing/requesting
Ensuring testing completed
Results included as part of MDT record
Planned as part of minimum data set
Especially with streamlined MDTs
Many ‘straightforward’ cases will be included but not necessarily discussed in future

4. But… Currently, not routinely included in many centres
GTAB/MTB
But…
Currently, not routinely included in many centres
May lack clinical details required to assess actionability
Or genomic findings not available when patient discussed in tumour MDT
Particularly with delay to return of 100K results currently being considered

5. Genomic Tumour Advisory Board (GTAB)
GTAB/MTB
Genomic Tumour Advisory Board (GTAB)
Triage results of WGA with benefit of up to date clinical information
Curative/relapsed/metastatic/dead
Decide which findings are potentially clinically actionable and should be validated
Report back to treating clinical team/MDT

6. Membership Recommended as minimum:
GTAB/MTB
Membership
Recommended as minimum:
Pathologist with cancer genomics expertise
Oncologist/haematologist with cancer genomics expertise
Clinical scientist/molecular pathologist with knowledge and expertise in NGS/cancer genomic testing
If this expertise is not available locally
Suggested could tap into national expertise, especially if running tumour specific GTABs

7. Other members recommended
GTAB/MTB
Other members recommended
Oncologist/haematologist involved in the treatment of patient under review
Clinical geneticist and/or GC with interest in cancer genomics
GTAB administrator/co-ordinator
Bioinformatician specialising in NGS and cancer genomics

8. Recommended terms of reference
GTAB/MTB
Recommended terms of reference
Ensure WGS and other genomic results are reviewed and interpreted
Appropriately and consistently
Perform initial triage following WGS data analysis by host laboratory
Ensure significant and potentially actionable results are identified from WGA (incl germline)
Ensure potentially actionable findings are considered in context of up to date clinical info and results of SOC testing for patient

9. GTAB/MTB
TOR continued
Ensure technical validation of findings initiated and reported as per local and national policy when required
To ensure feedback of validated results to appropriate clinician or MDT as per local policy
Ensure that discussions and outcomes are recorded appropriately and form part of the patient’s notes with appropriate caveats
Ensure necessary project outcome data and measures returned to GeL

10. GTAB/MTB
Frequency of meetings?
Currently – dependant on results release/work-up
Some GMCs holding ad-hoc, others regular (some yet to begin)
When routine WGS as part of diagnostic patient care, likely to need more frequent meetings

11. How does this work in practice??
GTAB/MTB
How does this work in practice??
WLGMC
Weekly time slot for meeting
Teleconference
2 co-chairs (both medical oncologists with expertise in cancer genomics)
Cases circulated in advance by GTAB co-ordinator
Also circulated to clinicians so can join to discuss their cases

12. Current working practice
GTAB/MTB
Current working practice
Cases prepared and reported by senior clinical scientist
Includes accessing up to date clinical information
Confirmation of pathology and SOC testing
Discussion of current clinical situation influences validation recommendation
Discussion of variants/implications
Consideration of clinical trials
Recommendation of GTAB documented and put into patient file

13. Disclaimer … because things will change
GTAB/MTB
Disclaimer … because things will change
This assessment is based on the available knowledge base at the time of the report and further updated versions may be produced – please check the electronic patient record for the most up-to-date version

14. If inadequate clinical details provided
GTAB/MTB
If inadequate clinical details provided
Or doubt raised about histopathological subtype
Returned to appropriate team for further work up
Brought back to GTAB when adequate documentation available for review
Also if SOC testing awaited – reviewed in light of routine diagnostic testing

15. GTAB/MTB
GTAB outcomes
Components of WGS examined eg preliminary and supplementary analysis
Clearly document if any of the supplementary analysis has been reviewed by GTAB
Date of WGA analysis (important for context)
Clear description of which variants validated and which have NOT been validated and should not be used clinically
Disclaimers (eg research only if not validated in accredited facility)

16. WGA outcomes no variants of potential clinical significance
GTAB/MTB
WGA outcomes
no variants of potential clinical significance
Variant(s) of potential clinical significance identified, further validation not required at time due to patient’s clinical situation
Variant of clinical significance/potential clinical significance identified, for validation due to patients current clinical situation
Variant of potential clinical significance identified that cannot be easily validated (eg TMB)
Variant of potential clinical significance identified that would ensure eligibility for clinical trial

17. Pitfalls or potential problems
GTAB/MTB
Pitfalls or potential problems
Currently:
Takes up 1-2 hours/week of clinician time in GTAB
Plus additional time for clinical scientist gathering data
Expected that this will increase as results needed to be reviewed increase
Routine WGS
Large panel testing

18. ? Need to include in job plans for core GTAB members
GTAB/MTB
? Need to include in job plans for core GTAB members
As MDT attendance is included
Difficulty with attendance from some specialty groups/clinicians
?need to make compulsory in future if their cases are discussed
Especially if regional MDTs considered?

19. GTAB/MTB
National GTABs?
May need to consider for sarcoma or paediatric cancer testing
Could run similar to the neonatal testing
Each GMC given a specific time to dial in
Core members attend for all of MDT, others just when their cases are discussed
Use of national expertise for rare conditions

20. Regional differences Core MDT makeup Reporting of results
GTAB/MTB
Regional differences
Core MDT makeup
Reporting of results
Interaction with hospital records
Individuals to whom results are fed back
?clinical trial eligibility
Should this be on wider basis??

21. GTAB/MTB
Thoughts and comments?

22. Feedback Received
Role of newly published ESCAT guidelines could be considered in clinical actionability of variants