GTAB/MTB working and terms of reference Angela George

GTAB/MTB working and terms of reference Angela George

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

? 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?

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

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??

GTAB/MTB Thoughts and comments?

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