Peter JohnsonOn behalf of the CR UK Stratified Medicine Programme

Molecular diagnosis of cancer: Making it a reality

The march of technology…

Single genes

Gene panels

Whole exomes

Whole genomes

Plus expression profiling, copy number variation, epigenetics, miRNA profiles…

EGFR experience shows gradual test adoption even when funding is agreed

Source: 12 months experience of EGFR testing in the UK, R. Butler, AstraZeneca et al, 2010

Background to the Programme

SOMATIC MUTATION TESTING FOR PREDICTION OF TREATMENT RESPONSE IN PATIENTS WITH SOLID TUMOURS:

– Already happening and demand predicted to increase– Funding not well established and access variable across the UK– Published data from quality assurance schemes suggest issues

with the reproducibility and accuracy – Needs to work in formalin-fixed, paraffin embedded tissue– Needs to take account of multiple potential targets in each

tumour– Little consensus on who to test, how to test, what to test or

how to interpret and report the results

Service delivery

component

Research infrastructure

The Stratified Medicine Programme pilot study combines service delivery and research components

Central data repository (ECRiC)

Current gene list and technology

Stratified Medicine Programme Patient Dataset

Derived from the core NHS Cancer Outcomes and Services Dataset (COSD):

– New NHS information standard; mandation and stepwise implementation from January 2013

– Linked to modernisation of the cancer registries with creation of a unified National Cancer Registration Service in England

– Sections for demographics, diagnosis, imaging, pathology, treatment and outcomes data

– Aim for automated data collection and extraction as far as possible

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Oct-12 Nov-12 Dec-12

Monthly recruitment 673 708 455

Monthly samples sent

384 400 635*

Monthly results returned

518 340 451

Paired samples

63 (1.5%)

68 (1.5%)

69 (1.3%)

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Results from the first 1000 casesProportion of tumours with sequence variation by type

Data analysis: Breast cancer

260 sequence abnormalities detected in samples from 246 patients

Data analysis: Colorectal cancer

Data analysis: Lung cancer

Pennell N A JOP 2012;8:34s-37s

NOS = not otherwise specified

Findings from the Stratified Cancer Medicine programme

• General acceptability to patients: over 98% consent

• Key role of clinical teams for each tumour type

• Critical role of pathology department in managing tissue samples

• Impact of mass testing in technology hubs

• Value of QA system

• Highly variable sample quality, with impact on test failure rates

• Complexities of NHS IT. XML messaging protocols

• Automated data extraction not yet reliable

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Challenges of obtaining the SM Programme patient dataset from routine clinical data• Data reflects the patient pathway with a multitude of one-to-many relationships: repeating identifiers required in submitted data to ensure linkage in database• Difficulty in sourcing some data items e.g. histopathology data, co-morbidity scoring, performance status• Lack of inter-operability between information technology systems used in histopathology and other parts of the electronic patient record • Use of Read codes and different versions of SNOMED• Cross-border data issues: problems sourcing some demographic details

Future Priorities

• Improve completeness, linkage and standardization of submitted data • Defining minimum sample requirements • Optimising test turnaround times • Moving towards routine commissioning of tests of proven utility• Development of multiplex technology for parallel analysis of many genes• Expansion of early phase therapy portfolio to exploit the molecular findings

Acknowledgements

• The patients who have consented to take part in the programme• Lead investigators and teams at the clinical and technology hubs• Stratified Medicine Programme team at CR-UK HQ• Dr Jem Rashbass and team, National Cancer Registration Service•Funding partners AstraZeneca and Pfizer