Queensland research is advancing ctDNA testing as a tool to detect clinically actionable mutations in blood samples from patients with NSCLC.
The cross-sectional study applied the UltraSEEK lung panel (Agena Bioscience), which detects 73 clinically relevant variants across BRAF, EGFR, ERBB2, KRAS and PIK3CA genes, to samples from 103 patients with advanced NSCLC undergoing systemic therapy.
Blood-based mutational findings were compared to pathology reporting of lung tissue mutations.
The study found tumour and blood concordance in the detection of KRAS mutations in 63% of patients and EGFR mutations concordance in the tumour and blood of 80% of patients.
In 56 patients where no mutations were reported in the primary tumour, the UltraSEEK lung panel identified mutations in 19.6% of patients.
“This findings highlight where ctDNA assessments may be useful, especially in instances where exon-19 deletion or T790M mutated tumours are present and there may be limitations in accessing sufficient tissue for this assessment,” the investigators said.
The study, published in Lung Cancer, also tracked ctDNA longitudinally in four patients over the course of their therapy and found the individual mutations mirrored the response to therapy/progression of disease.
For example: “In case A, an increase in the KRAS_pG12R mutation between the pre-treatment blood sample to FU1, showed that the patient had developed progressive disease (PD).”
“In case B, the response to gemcitabine and carboplatin was demonstrated by the fall in KRAS_pG12R for a partial response (PR).”
“Importantly, this highlights the need to track multiple mutations over time as some may emerge, and are not present early on in disease, and some may reflect tumoural changes under the stressors of treatment.”
The study said ctDNA testing was minimally invasive compared to tissue biopsy, can be repeated serially over the course of treatment to monitor response to therapy and detect minimal residual disease (MRD) post curative treatment.
“Whilst preliminary, this study demonstrates the utility of detecting clinically actionable mutations in the blood samples of NSCLC patients at the time of presentation, and over the course of therapy,” the study concluded.
The study was led by Dr Arutha Kulasinghe from the Centre for Genomics and Personalised Health at the Queensland University of Technology and Translational Research Institute.