Abstract 3292
Background
Evaluating tumor RAS/RAF status is essential for treatment selection and prognosis evaluation in metastatic colorectal cancer (mCRC) patients. Analyzing ctDNA in mCRC patients has many advantages because of its non-invasive nature. However, since the signal of ctDNA is generally low, detection of ctDNA from different platforms need to be carefully interpreted before adapting new technology into routine clinical application.
Methods
60 mCRC patients under different treatment status were recruited. A cross-platform comparison between MALDI-TOF (UltraSEEK) and next-generation sequencing (NGS) was done by examining KRAS/NRAS/BRAF/PIK3CA mutations frequency in plasma from patients. Inconsistent results between two platforms were examined by droplet digital polymerase chain reaction (ddPCR). All results were compared to the mutation status in tissue retrospectively.
Results
In the comparison between NGS and MALDI-TOF, we focused on 65 hotspots, 53.57% and 60.71% of the samples were reported to be positive by NGS and MALDI-TOF respectively. Concordance rate between two platforms was 73.21%. Discrepancy between two platforms was examined by ddPCR, and a reproducible result was then treated as a true positive. The PPA of NGS and MALDI-TOF was 93.94%, 90.91 %; NPA of NGS and MALDI-TOF was 99.97%, 99.63 %, respectively. After establishing a ground truth for plasma result, 56 patients were found to have comparable ARMS result from tissue. Apart from 10 patients undertaking chemotherapy or Cetuximab, 95.6% (44/46) patients have their plasma result consistent with that from tissue. For 10 patients undergoing treatment at the time of plasma acquisition, ctDNA status detected by NGS was showed to be an effective biomarker to monitor the response to treatment: 90% (9/10) of patients had a ctDNA status that were consistent with their progression status.
Conclusions
ctDNA detected by NGS was showed to be a reliable signal that reflects tumor burden and informs treatment response. Even challenge exists in detecting variants in low frequency in plasma, appropriate selection of technology allows reliable examination of clinical utility in upcoming clinical studies.
Clinical trial identification
Legal entity responsible for the study
Zhongshan Hospital, Fudan University.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.