Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma

Table 1 Baseline characteristics of patients

Variables	n = 135
Age, years, median (IQR)	71 (65-76)
Sex, male/female	70/65
Baseline CA19-9, U/mL, median (IQR)	76.6 (21.3-258.2)
Preoperative CA19-9, U/mL, median (IQR)	30.9 (11.6-100.2)
1Resectability status, resectable/BR	91/44
Tumor location, Ph/Pb/Pt	98/29/8
Neoadjuvant therapy, present	109
Chemotherapy, present	99
Chemoradiotherapy, present	10
Baseline tumor size, mm, median (IQR)	22.5 (17-30)
Preoperative tumor size, mm, median (IQR)	18 (13.8-25)

¹According to the National Comprehensive Cancer Network criteria.

BR: Borderline resectable; IQR: Interquartile range; Pb: Pancreatic body; Ph: Pancreatic head; Pt: Pancreatic tail; CA19-9: Carbohydrate antigen 19-9.

Table 2 Comparison of clinicopathological factors between the circulating tumor DNA positive and negative groups

Variables	ctDNA + (n = 35)	ctDNA - (n = 100)	P value
Age, years, median (IQR)	72 (65-77)	71 (66-76)	0.846
Sex, male/female	23/12	47/53	0.057
Baseline CA19-9, U/mL, median (IQR)	79.9 (18.0-236)	71.2 (21.5-267.6)	0.891
Preoperative CA19-9, U/mL, median (IQR)	30.9 (12.3-125.2)	30.5 (11.3-97.5)	0.572
1Resectability status, resectable/BR	29/6	62/38	0.023
Tumor location, Ph/Pb/Pt	26/9	72/28	0.794
Neoadjuvant therapy, absent/present	10/25	16/84	0.105
Baseline tumor size, mm, median (IQR)	21 (15-26)	23 (17-30)	0.145
Preoperative tumor size, mm, median (IQR)	17 (14-25)	19 (13-25)	0.442
2Pathological T factor, 1/2/3	11/14/5	31/52/11	0.551
2Regional lymph node metastases, 0/1/2	14/11/5	45/35/14	0.973
Post operative therapy, absent/present	5/30	13/87	0.847
Occult metastases, absent/present	18/17	20/80	0.001

¹According to the National Comprehensive Cancer Network criteria.

²According to the Union for International Cancer Control tumor node metastasis classification 8^th edition. Excluded ten patients who had not undergone pancreatectomy.

ctDNA: Circulating tumor DNA; BR: Borderline resectable; IQR: Interquartile range; Pb: Pancreatic body; Ph: Pancreatic head; Pt: Pancreatic tail; CA19-9: Carbohydrate antigen 19-9.

Table 3 Univariate and multivariate analyses of preoperative factors related to occult metastases

Factors	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
Age, ≥ 70 (years)	0.99	0.46-2.13	0.975
Sex, male	1.21	0.57-2.57	0.620
Tumor location, Pb, Pt	1.11	0.48-2.56	0.802
1Resectability status, BR	0.66	0.29-1.52	0.332
Neoadjuvant therapy, yes	1.82	0.63-5.25	0.265
Preoperative CA19-9, ≥ 150 (U/mL)	3.08	1.28-7.41	0.012	2.89	1.10-7.61	0.031
Preoperative tumor size, ≥ 29 (mm)	3.03	1.10-8.37	0.032	2.82	0.92-8.64	0.069
ctDNA, positive	4.23	1.86-9.66	0.0006	4.96	2.07-11.90	< 0.001

¹According to the National Comprehensive Cancer Network criteria.

OR: Odds ratio; CI: Confidence interval; ctDNA: Circulating tumor DNA; BR: Borderline resectable; Pb: Pancreatic body; Pt: Pancreatic tail; CA19-9: Carbohydrate antigen 19-9.