Preoperative risk stratification of early recurrence in resected pancreatic ductal adenocarcinoma: Novel equilibrium-phase-computed tomography biomarker of extracellular volume

Table 1 Baseline characteristics of patients with pancreatic ductal adenocarcinoma, mean ± SD/n (%)

Characteristic	Non-ER (n = 47)	ER (n = 46)	P value
Age (years)	60.76 ± 1.50	61.27 ± 1.33	0.802
Male sex	29 (61.7)	29 (63.0)	0.867
Female sex	18 (38.3)	17 (37.0)	0.894
BMI (kg/m2), IQR	21.85 (20.50-23.93)	21.78 ± 4.70	0.895
Type of pancreatic surgery			0.165
Standard pancreatic surgery	42 (89.4)	37 (80.4)
Extended pancreatic surgery	5 (10.6)	9 (19.6)
Laboratory results
CA19-9 (U/mL), IQR	54.37 (15.48-268.88)	328.00 (90.45-500.00)	0.006
Haematocrit level (%), IQR	38.80 ± 7.86	38.00 (34.55-41.45)	0.339
Bilirubin (μmol/L), IQR	47.05 (12.98-159.25)	64.00 (10.20-201.55)	0.809
Albumin (g/L), IQR	40.50 (37.00-44.75)	38.97 ± 1.14	0.161
Lymphocytes (109/L), IQR	24.41 ± 1.38	19.50 (14.75-30.75)	0.207
Alkaline phosphatase (μkat/L), IQR	188.0 (88.0-428.0)	154.00 (87.00-461.00)	0.913
Tumor location			0.077
Head	31 (66.0)	37 (80.4)
Body/tail	16 (34.0)	9 (19.6)
Tumor size (cm), IQR	2.0 (1.50-3.50)	2.8 (2.25-3.90)	0.024
AJCC tumor stage			0.867
I	31 (66.0)	31 (67.4)
II/III	16 (34.0)	15 (32.6)
Tumor grade			0.006
G1/2	32 (68.1)	19 (41.3)
G3	15 (31.9)	27 (58.7)
Postoperative adjuvant therapy	26 (49.1)	27 (50.9)	0.430
ΔHUtumor, IQR	53.05 ± 3.43	37.00 (32.66-45.00)	0.003
CT-derived ECV (%)	39.78 ± 1.95	30.01 ± 1.90	0.001
CT findings of the pancreas
Ill-defined margins	13 (27.7)	13 (28.3)	0.948
Main pancreatic duct dilation	21 (44.7)	20 (43.5)	0.979
Parenchymal atrophy	7 (14.9)	11 (23.9)	0.271
Vein abutment	9 (19.1)	17 (37.0)	0.056
Peripancreatic tumor infiltration	11 (23.4)	18 (39.1)	0.102

ER: Early recurrence; IQR: Interquartile range; BMI: Body mass index; CA19-9: Carbohydrate antigen 19-9; ECV: Extracellular volume; HU: Hounsfield unit; ΔHU_tumor: Absolute enhancement of the tumor attenuation between the unenhanced and equilibrium-phase computed tomography images; CT: Computed tomography; AJCC: American Joint Committee on Cancer; G1: Well differentiated; G2: Moderately differentiated; G3: Poorly differentiated.

Table 2 Univariate and multivariate analyses for early recurrence in patients with pancreatic ductal adenocarcinoma

Variable	Univariate analysis		Multivariate analysis
	Hazard ratio (95%CI)	P value	Hazard ratio (95%CI)	P value
Age (years)	1.008 (0.974-1.042)	0.660
Male sex	0.842 (0.429-1.650)	0.616
Postoperative adjuvant therapy	0.734 (0.423-1.274)	0.272
CA19-9 (U/mL)	1.001 (1.000-1.001)	0.050	1.000 (1.000-1.001)	0.002a
Tumor location		0.131
Head	1 (Reference)
Body to tail	0.404 (0.125-1.310)
Tumor size (cm)	1.196 (0.959-1.492)	0.112
T stage		0.003		0.319
T1	1 (Reference)		1 (Reference)
T2 + T3	3.256 (1.499-7.071)		1.556 (0.652-3.712)
N, yes	1.211 (0.578-2.539)	0.612
Tumor grade, G3	2.542 (1.352-4.780)	0.004	2.506 (1.204-5.215)	0.014a
AJCC tumor stage		0.942
I	1 (Reference)
II/III	0.975 (0.498-1.912)
CT findings of the pancreas
Ill-defined margins	0.987 (0.511-1.905)	0.968
Main pancreatic duct dilation	0.895 (0.485-1.652)	0.723
Parenchymal atrophy	1.306 (0.654-2.609)	0.449
Vein abutment	1.778 (0.954-3.313)	0.070	2.099 (0.977-4.510)	0.057
Peripancreatic tumor infiltration	0.762 (0.441-1.315)	0.329	0.879 (0.530-1.457)	0.616
ΔHUtumor	0.974 (0.958-0.990)	0.002	0.988 (0.965-1.013)	0.340
CT-derived ECV (%)	1.057 (1.025-1.090)	0.001	1.050 (1.017-1.085)	0.003a

^aP < 0.05.

CA19-9: Carbohydrate antigen 19-9; ECV: Extracellular volume; HU: Hounsfield unit; CT: Computed tomography; AJCC: American Joint Committee on Cancer; ΔHU_tumor: Absolute enhancement of the tumor attenuation between the unenhanced and equilibrium-phase computed tomography images; N: Lymph nodes; CI: Confidence interval; G3: Poorly differentiated.

Table 3 The efficacy of each parameter in predicting early recurrence

Characteristic	Combined ECV and CA19-9	CT-derived ECV	CA19-9	Tumor grade
Cutoff value	0.45	35.37	55.00	Ref.
AUC (95%CI)	0759 (0.653-0.846)	0.736 (0.628-0.827)	0.686 (0.575-0.784)	0.650 (0.538-0.752)
Sensitivity	87.80	80.49	90.24	60.98
Specificity	69.52	59.42	45.24	69.05
P value	< 0.001	< 0.001	0.002	0.005

CA19-9: Carbohydrate antigen 19-9; ECV: Extracellular volume; CT: Computed tomography; AUC: Area under the curve; CI: Confidence interval.