Advances in science and technology have made precision oncology using molecular diagnostics a genuine option of remarkable potential to benefit patients. Even as concepts and technical requirements are developed, however, massive organizational and logistical challenges remain. In this chapter we describe the challenges of implementing stratified medicine in the UK, by highlighting phase 1 of the Cancer Research UK Stratified Medicine Programme (SMP1) as an example.
SMP1 was set up as a collaborative academic and industry project, with the aim of undertaking large-volume genetic testing across the UK in order to demonstrate our potential to build a national molecular diagnostics platform: recruiting patients, processing routine pathological material, returning molecular data and collecting clinical information.1,2 To do this, an ambitious recruitment target of approximately 9000 patients from across the UK over a 2 year period (2011–2013) was set. The positive aspects of such an infrastructure for cancer patients are illustrated in particular by the example set by the French National Cancer Institute.3 It was appreciated at inception that many clinicians would benefit from a system where upfront genetic results could save time spent on treatment planning: for example, avoidance of delay in the choice between epidermal growth factor receptor (EGFR) inhibition and chemotherapy in first line treatment of advanced non-small-cell lung carcinoma (NSCLC).
An expansive biotechnological, clinical and information technology network was organized to undertake SMP1: 10,754 patients were recruited across 26 hospitals supported by eight clinical hubs (Birmingham, Cambridge, Cardiff, Edinburgh, Glasgow, Leeds, Manchester, Royal Marsden/Brompton), with 9010 samples ultimately sent for testing. Within these samples, nearly 40,000 genes were tested in three technology hubs (Birmingham, Cardiff, Royal Marsden/Institute of Cancer Research). Genetic testing was tailored according to a recruitment strategy that targeted patients with a presumed/confirmed diagnosis of the following cancers: breast cancer (TP53, PTEN, PIK3CA, BRAF), lung cancer (KRAS, EGFR, EML4-ALK, BRAF, DDR2), colorectal cancer (KRAS, NRAS, BRAF, PIK3CA, TP53), prostate cancer (TMPRSS2-ERG, BRAF, PTEN), ovarian cancer (TP53, PTEN, PIK3CA, BRAF) and melanoma (BRAF, NRAS, KIT, PI3KCA). Patients with all stages of each cancer were eligible.
Outcomes from the programme include a range of data relating to the process of SMP1 implementation, as well as more translational information such as examination of the association between genetics and pathological/demographic characteristics, the propensity for gene aberrations to occur together or independently from one another, and the concordance of gene results between paired tissue samples taken from a limited number of patients in each cancer-based cohort. Details of cancer-specific translational results will be reported elsewhere (Br J Cancer. Submitted for publication).
Core results related to the implementation of the programme include the following.