Contrast-Enhanced CT Parameters of Gastric Adenocarcinoma: Can Radiomic Features Be Surrogate Biomarkers for HER2 Over-Expression Status?

Figures & data

Figure 1 NC-CT and CE-CT scans of GACs.

Notes: CT images in the non-contrast phase (A), arterial phase (B), portal venous phase (C), and delayed phase (D) showed a thickened gastric wall. The thickened gastric wall was targeted as the ROI. The ROI was manually drawn along the margin of the lesion (red line).

Table 1 Clinicopathological Characteristics of Patients with GACs, Median (Range) or n (%)

Characteristic	Total (n=460)	HER2 Positive (n=84)	HER2 Negative (n=376)	P value
Gender
Male/Female	353/107	64/20	289/87	0.887
Age (years)	66 (29–89)	66 (43–87)	65.5 (29–89)	0.273
Location
Cardia and fundus	83 (18.0)	20 (23.8)	63 (16.8)	0.129
Body	113 (24.6)	26 (31.0)	87 (23.1)	0.133
Antrum and pylorus	246 (53.5)	35 (41.7)	211 (56.1)	0.016
Whole stomach	18 (3.9)	3 (3.6)	15 (4.0)	1.000
Maximum diameter of tumor (cm)	4.3 (0.5–14.0)	5.0 (1.0–12.5)	4.0 (0.5–14.0)	0.122
Differentiation degree
Differentiated type	112 (24.3)	40 (47.6)	72 (19.1)	<0.001
Mixed type	114 (24.8)	24 (28.6)	90 (23.9)	0.374
Undifferentiated type	234 (50.9)	20 (23.8)	214 (56.9)	<0.001
Vascular invasion status
Yes/No	167/293	23/61	144/232	0.060
Neural invasion status
Yes/No	151/309	21/63	130/246	0.091
Pathological T stage
T1	54 (11.7)	14 (16.7)	40 (10.6)	0.121
T2	64 (13.9)	11 (13.1)	53 (14.1)	0.811
T3	315 (68.5)	54 (64.3)	261 (69.4)	0.360
T4	27 (5.9)	5 (6.0)	22 (5.9)	1.000
Pathological N stage
N0	138 (30.0)	32 (38.1)	106 (28.2)	0.073
N1	84 (18.3)	13 (15.5)	71 (18.9)	0.465
N2	113 (24.6)	20 (23.8)	93 (24.7)	0.859
N3	125 (27.2)	19 (22.6)	106 (28.2)	0.299
Pathological M stage
M0	436 (94.8)	81 (96.4)	355 (94.4)	0.593
M1	24 (5.2)	3 (3.6)	21 (5.6)
TNM stage
I	104 (22.6)	22 (26.2)	82 (21.8)	0.385
II	132 (28.7)	27 (32.1)	105 (27.9)	0.440
III	199 (43.3)	32 (38.1)	167 (44.4)	0.291
IV	25 (5.4)	3 (3.6)	22 (5.9)	0.405

Abbreviations: T, tumor; N, lymphoma node; M, metastasis.

Table 2 Dynamic CT Parameters of Patients with GACs, Mean (±SD)

Parameters	Total (n=460)	HER2 Positive (n=84)	HER2 Negative(n=376)	P value	Correlation Coefficient(CC) with HER2 Status	P value
Non-contrast phase
CAV (HU)	37.91 (±7.81)	35.74 (±8.11)	38.40 (±7.66)	0.005	−0.135	0.004
Arterial phase
CAV (HU)	64.07 (±15.92)	69.64 (±16.61)	62.82 (±15.51)	<0.001	0.172	<0.001
cCAV	0.24 (±0.07)	0.26 (±0.07)	0.24 (±0.07)	0.003	0.141	0.002
Portal phase
CAV (HU)	83.71 (±18.37)	86.94 (±16.67)	82.99 (±18.67)	0.075	0.093	0.047
cCAV	0.61 (±0.13)	0.62 (±0.12)	0.60 (±0.13)	0.194	0.050	0.284
Delayed phase
CAV (HU)	79.51 (±17.90)	80.79 (±18.51)	79.21 (±17.77)	0.466	0.032	0.490
cCAV	0.70 (±0.14)	0.70 (±0.16)	0.69 (±0.14)	0.593	0.001	0.975

Abbreviations: SD, standard deviation; CAV, CT attenuate value; cCAV, corrected CT attenuate value; HU, Hounsfield unit.

Figure 2 CT parameters between two different HER2 expression groups were compared.

Notes: (A) The CAVs were significantly different between 2 groups in non-contrast (p = 0.005) and arterial (p < 0.001) phases. (B) The cCAVs were significantly different between 2 groups in arterial (p = 0.003) phase. ***p < 0.01.

Table 3 Diagnostic Performance of CT Parameters in Distinguishing the HER2 Status

Parameters	Cut-Off	Sensitivity	Specificity	AUC	P value
Non-contrast phase
CAV	32.29	0.822	0.345	0.601	0.004
Arterial phase
CAV	67.36	0.583	0.657	0.628	<0.001
cCAV	0.255	0.500	0.694	0.605	0.003
Portal phase
CAV	70.37	0.869	0.271	0.569	0.047
cCAV					0.283
Delayed phase
CAV					0.489
cCAV					0.975

Abbreviations: AUC, area under the receiver operating characteristic curve; CAV, CT attenuate value; cCAV, corrected CT attenuate value.

Table 4 Univariate and Multivariate Logistic Regression Analysis for Patients with Gastric Adenocarcinomas

Variable	Univariate Analysis		Multivariate Analysis
	Crode OR (95% CI)	P value	Adjust OR (95% CI)	P value
Gender (male vs female)	1.038 (0.595–1.811)	0.895
Age (≥65 vs <65; years)	0.909 (0.566–1.460)	0.693
Location
Cardia and fundus	1.587 (0.417–6.048)	0.498
Body	1.494 (0.401–5.564)	0.549
Antrum and pylorus	0.829 (0.228–3.013)	0.776
Whole stomach	1
Maximum diameter of tumor(cm)	1.087 (0.992–1.190)	0.073	1.126 (1.021–1.242)	0.017
Differentiation degree
Differentiated type	5.944 (3.264–10.826)	<0.001	5.505 (2.942–10.302)	<0.001
Mixed type	2.853 (1.501–5.425)	0.001	2.843 (1.479–5.463)	0.002
Undifferentiated type	1		1
TNM stage
I	1.967 (0.539–7.182)	0.306
II	1.886 (0.525–6.770)	0.331
III	1.405 (0.397–4.975)	0.598
IV	1
Vascular invasion status (yes vs no)	0.607 (0.360–1.025)	0.062	0.734 (0.408–1.320)	0.301
Neural invasion status (yes vs no)	0.631 (0.368–1.080)	0.093	0.901 (0.492–1.648)	0.734
CAV in non-contrast phase (≥32.29 vs <32.29; HU)	0.411 (0.244–0.693)	0.001	0.477 (0.273–0.832)	0.009
CAV in arterial phase* (≥67.36 vs <67.36; HU)	2.681 (1.653–4.346)	<0.001	2.583 (1.548–4.310)	<0.001
cCAV in arterial phase* (≥0.255 vs <0.255)	2.270 (1.403–3.670)	0.001	2.348 (1.404–3.927)	0.001
CAV in portal phase* (≥70.37 vs <70.37; HU)	2.470 (1.260–4.845)	0.008	3.188 (1.52–6.462)	0.001

Notes: *These analyses were done in separate multivariate Cox regression analyses, including patient characteristics like maximum diameter of tumor, differentiation degree, vascular and neural invasion status, besides the CAV in non-contrast phase. These analyses' results were listed in Table S1.

Abbreviations: CAV, CT attenuate value; cCAV, corrected CT attenuate value; OR, odd ratio.