An ultrasensitive method for measuring circulating tumour DNA (ctDNA) in blood samples was shown to quantify cancer burden in non–small-cell lung cancer (NSCLC) report US scientists in Nature Medicine.

Analysis of ctDNA offers the potential to revolutionizer detection and monitoring of tumours, with non invasive access to cancer-derived DNA considered a particularly attractive approach for solid tumours, which cannot be repeatedly sampled without invasive procedures.

Existing ctDNA detection methods, however, have proved insufficiently sensitive for broad clinical applicability.

In NSCLC, PCR-based assays have been used to detect recurrent point mutations in genes such as KRAS or EGFR, but have proved of limited value since many patients lack mutations in these genes.

Maximilian Diehn and colleagues, from Stanford University, California, developed a new approach for ctDNA analysis; Cancer Personalised Profiling by Deep Sequencing (CAPP-Seq) that targets recurrently mutated regions in the cancer of interest.

Using samples taken from over 400 NSCLC patients they first identified recurrent gene mutations.

Then taking samples from another set of patients with stage I, stage II and advanced NSCLC, they were able to detect ctDNA with high specificity.

The amounts of ctDNA measured, they found, correlated with tumour volumes during the course of therapy, identified patients with residual disease after treatment, and better detected response to therapy compared to radiographic methods.

In the study they were able to accurately identify around 50% of people with stage I lung cancer and all patients whose cancers were more advanced.

“We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalised cancer therapy,” write the authors, adding that the approach achieves both an ultralow detection limit and broad patient coverage at a reasonable cost.

Reference

A Newman, S Bratman, J To, et al An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nature Medicine.

Published online 6 April 2014; doi:10.1038/nm.3519