Table 7.

ctDNA as a quantitative monitoring tool in predicting response to treatment.

	Study Design	Sample Size	Study Population	ctDNA Detection Method	PFS
Predicting response to treatment	Prospective, multi-center study [71]	28	Stage IV CRC	ddPCR NGS * (Ion AmpliSeq Cancer Hotspot Panel)	ctDNA−: 4.0 months ctDNA+: 1.9 months Hazard ratio, 0.44; 95% CI, 0.18–0.98; p = 0.03)
	Clinical trial [72]	29	Stage IV CRC	Guardant 360 ** assay	ApCN ≥ 25.82: 22.5 weeks ApCN ≤ 25.82: 14.8 weeks Mantel Cox, p = 0.0347
	Prospective study [73]	467	Stage IV CRC	Methy-Light	No effect on PFS
	Prospective study [74]	53	Stage IV CRC	Safe-SeqS	≥10-fold reduction in ctDNA: 14.7 months ≤10-fold reduction in ctDNA: 8.1 months Hazard ratio, 1.87; 95% CI, 0.62–5.61; p = 0.266
	Prospective (PLACOL) study [61]	82	Stage IV CRC	ddPCR	“good ctDNA responder” = ctDNA concentration < 0.1 ng/mL and SlopeΔctDNA ≥ 80%: 8.5 months “bad ctDNA responder” = ctDNA concentration > 0.1 ng/mL and SlopeΔctDNA < 80%: 2.4 months Hazard ratio, 0.19; 95% CI, 0.09–0.40; p < 0.0001
	Prospective study [75]	45	Stage IV CRC	dPCR (Methyl-BEAMing)	A negative change in ctDNA is associated with improved PFS

Safe-SeqS: Safe-Sequencing System, ddPCR: droplet digital PCR, and ApCN: adjusted plasma copy number. * Ion Torrent S5 XL, Thermo Fisher Scientific; ** Guardant Health, Inc. Redwood City, CA, USA.