PMC6439419_01
KRAS G12/13 longitudinal monitoring and clinical response to anti-EGFR mAb plus chemotherapy in cell-free circulating DNA of a mCRC patient. (A) Computed tomography (CT) images of liver metastasis during anti-EGFR mAb treatment, holyday and mAb re-challenge. (B) Red line indicates the fractional abundance of KRAS mutation (percentage of mutated alleles in a total DNA background) detected in ctDNA at treatment course (X-axis) by ddPCR. Approximately 3,000 haploid genome equivalents were analyzed for each time point (KRAS limit of detection 0.5%). Gray columns represent CEA levels. KRAS mutation detection was able to anticipate clinical progression, preceding CEA elevation. (A,B)
KRAS levels decreased during anti-EGFR holyday and chemotherapy switch coinciding with stable disease. High levels of KRAS mutations after chemotherapy progression were able to predict poor response to anti-EGFR re-challenge. Cmab, cetuximab; Pmab, panitumumab; Chemo, chemotherapy; SD, stable disease; PD, progressive disease.
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At the beginning of CPT11/CTX treatment, in June 2015, blood samples were negative for the presence of KRAS mutations (Figure 1). KRAS mutations became detectable in September 2015, anticipating clinical disease progression, and raised considerably over the next 2 months reaching a fractional abundance of 33.8% in November 2015 (Figure 1). A significant increase in KRAS mutation fractional abundance was also observed during this period (from 33.8 to 70.7% in February 2016) (Figure 1). However, KRAS mutation abundance started to increase steadily thereafter, anticipating, once more, clinical disease progression (Figure 1). A significant increase in KRAS mutation abundance in ctDNA was observed after the interruption of palliative treatment (Figure 1).