Principal Investigators: Dr Robert Rintoul & Dr Nitzan Rosenfeld
Funded by: CRUK Early Detection Programme Award
Diagnosing non-small cell lung cancer (NSCLC) at an earlier stage can save lives. Circulating tumour DNA (ctDNA) can be detected in plasma of patients with early-stage cancer, but it is unclear how early it can be detected, or what analytical sensitivity is required to detect the majority of stage I-II cancers in blood. Ideally, performance should be assessed in samples collected prior to diagnosis; however prospective collection in the general population is costly and complex. Previous studies collected plasma from patients at or after diagnosis, analysed few mutated loci, and detected ctDNA in only a minority of stage I cancer patients. Recent findings suggest an important role for methylation of plasma cell-free DNA in non-invasive detection of cancer. We hypothesize that multiplexed analysis in plasma samples of 100s-1000s of somatic mutations, combined with analyses of methylation and other molecular biomarkers, could detect early-stage cancer months or years ahead of clinical diagnosis in a high-risk population. To test this hypothesis, we bring together an array of cutting-edge technologies for cancer molecular diagnostics, study samples we collected at diagnosis of early-stage NSCLC, and establish a clinical study to collect samples from patients who have been treated with curative intent for NSCLC and are at high risk for either recurrent disease or a second primary cancer.