Table 3.

Clinical relevance of ctDNA detection at baseline.

	Study	Tumor Stage	Rate of ctDNA Detection before Surgery	ctDNA Detection Method	Outcome
Tumor burden at diagnosis	[52]	I II III	50% 89% 90%	TEC-Seq	Patients with increased pre-operative ctDNA had a shorter PFS and OS compared to patients with a lower ctDNA (HR 1.13, 95% CI: 1.03–1.24)
	[32]		60% 56% 86%	ddPCR	8/10 ctDNA+ patients relapsed 6/11 ctDNA+ patients did not relapse
	[54]		64%	ddPCR	No relation between baseline ctDNA and DFS (HR 0.93, 95% CI: 0.33–2.69)
	[8]		60% 92% 90%	Multiplex PCR-based NGS	No significant association between ctDNA and the outcome
	[55]		30%	ddPCR	Pre-operative ctDNA was associated with inferior RFS (HR 2.18, 95% CI: 1.02–4.61)
	[30]		NM	Spectrophotometry (NanoDrop)	Significantly higher cfDNA levels were observed in patients, with early recurrence compared to non-recurrent patients
	[56]	II III	64%	NGS	Pre-operative ctDNA+ patients had reduced RFS compared with pre-operative ctDNA− patients (HR 5.66; 95% CI: 1.72–18.57)
	[57]		42%	ddPCR	Baseline ctDNA was an independent prognostic factor of DFS (HR 3.35, 95% CI: 1.15–9.77)
	[51]		25% 30%	ddPCR	The rate of recurrence was 32.7% in ctDNA+ patients and 11.6% in ctDNA− patients (p = 0.001)
	[53]		64% 74%	Real-time multiplex PCR assay	12/47 (25.5%) ctDNA+ patients relapsed

NGS: Next-Generation Sequencing, TEC-Seq: Targeted Error Correction Sequencing, and NM: not mentioned.