Cancer results pathway Jane Moorhead 30 October 2018

Patient Situation Discharged from regular oncological follow-up Currently receiving systemic anti-cancer therapy (not including adjuvant hormonal therapy) On regular surveillance and/or monitoring but no evidence of active cancer (includes patients who have completed SACT and/or currently on hormonal therapy) Known active cancer but not on systemic treatment at present On regular surveillance and/or monitoring (Deceased)

Results Received Definition of active management (most agreed that this included patients on hormone therapy) Most clinicians, who responded to survey, wanted all results, 1-6, although a significant number preferred only 2-5 above However clinicians feeding back on the survey were not necessarily recruiting clinicians and may not be representative of all

Forwarding the Report from MTB Difficulties in knowing who the appropriate clinician would be, especially with non FT results and also patients representing at a later stage, the MDM deemed better by most All** results should be fed back to the relevant MDM (many agreed) MDM can decide what they want to deal with, rationale being that they have best access to patient situation All metastatic patients should be discussed fully, all with active cancer +/- treatment Problem with the capacity of current system (work to be done with Martin Gore, RCPath on MDM review/rework).

LDPs No one on the call saw any particular problems with LDPs as they can join MTB and/or MDM by video link There have been reports from some of the larger centres, that are LDPs, that they have no idea where the results go and no input into the MTB Difficulties in finding the relevant clinicians at LDP – even more so than in hubs Is further work required on this?

Availability of Results All results should be recorded on EPR Need to clarify what is meant by results – validated only? All domain 1 mutations (for that cancer type), GL, mutational signature and mutational burden should be recorded? Line on EPR and MDM outcomes to say WGS results available Issues often arise with patients moving, notes following them or not One GMC is trying to get links to all EPRs relevant to them – possibly ok for smallish area but realistic for large??? Give patient a card to say that they participated GP to be informed Line on histopathology report to say 100K results available (and also to say fresh tissue taken) Comments regarding how relevant the sequence data is for relapsed patients especially following treatment

Results to Patient Who tells patient? If under active care, clinician (but see previous slides) If not under active care, GP suggested (extra resource, full understanding) or MDM lead If discharged should there be an extra hospital appointment for results discussion? All agreed that results need to be returned to the patient as they signed up for this, regardless of actionability, but especially pertinent germline findings NB Ensure that the clinicians feeding back are completely au fait with what the results comprise eg ‘pertinent’ GL rather than all A caveat should be added to say that secondary findings are not yet included

Future Perspectives Consideration of new targets coming on line Changes to patient situation occur with time so results needed far into future potentially Reanalysis a possibility

Other Comments Ideal MTB will have disease specific oncology and clinical genetics attending but is that realistic? Many other commitments and getting all together even by video link can be impossible All agreed that resources are an issue. Time taken by anyone whether scientist MDM co-ordinator etc. to find appropriate route for results is enormous Adding all patients to MDM not acceptable to some (who’s ultimate responsibility if MDM says no?). Most agree some triaging is essential No fool-proof way of returning results so possibly best to use as many of suggestions as possible Some centres are not happy with restricting access to data Post transition should be much smoother as patients will get tested if needed as now so result will be expected

Appendices

Feedback Received Appendix 1: It should be made clear that the workflow in Appendix 1 is a suggested minimum. This should not discourage GMCs from analysing WGS data from cancer patients who are currently in remission. Appendix 3: The exemplar provided should include the participants in the GTAB or equivalent or contact for where this information can be obtained Appendix 4: Tumour types where no relevant cancer susceptibility genes are examined for germline variants should be listed e.g. lung cancer. Appendix 4:What is indicated by the parentheses around CDK4 in melanoma? Appendix 11: What is meant by mutational burden for the KRAS variant as allele fraction is already listed? Should this be neoplastic cell content of the sample analysed?