Treatment and monitoring of patients with gastrointestinal stromal tumours using circulating tumour DNA

Gastrointestinal stromal tumours (GISTs) are rare but the most common mesenchymal malignancies of the gastrointestinal tract. Most tumours share a similar genetic profile. These oncogenic mutations in KIT or PDGFRα can be detected in circulating tumour DNA (ctDNA) in the blood plasma. Pieter Boonstra described the design of a single-tube droplet digital PCR (ddPCR) assay to detect the most common KIT exon 11 mutations in tumour and ctDNA used for treatment-decision-making. Using this assay, Boonstra showed that changes in levels of these mutations in plasma correspond well with tumour response defined with routine CT-scanning in GIST patients with metastatic disease. Monitoring of treatment response was also illustrated by changes of ctDNA levels using a ddPCR assay for patient-specific PDGFRα mutations. Furthermore, he showed the added value of ctDNA in the diagnostic setting when tumour biopsy is not feasible. Boonstra also studied some critical factors during processing of circulating tumour DNA from plasma, and he showed significant differences when comparing three commonly used ccfDNA extraction methods. His work demonstrates the need of harmonization and standardization of procedures using liquid biopsies before these new applications can be routinely implemented in the clinical setting.