Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer

Table 1 Patients’ characteristics n (%)

Characteristics	P value
Age (yr), mean ± SD (range)	65 ± 10 (30-85)
Gender
Male	197 (58)
Female	145 (42)
Length of follow-up (mo), median (IQR)	11 (6-24)
Venous thromboembolism
Pulmonary embolism	9 (2.6)
Deep venous thrombosis	22 (6.4)
Portal vein thrombosis	2 (0.6)
Port-a-Cath	1 (0.3)
Cumulative frequency	34 (9.9)
Khorana Class of risk
Low	199 (58)
Intermediate	118 (35)
High	25 (7)
Site of primary
Colon-rectum	237 (69)
Stomach	38 (11)
Pancreas	36 (11)
Biliary tract	16 (5)
Oesophagus	15 (4)
Stage of disease
Primary	142 (42)
Metastatic	200 (58)
Performance status (ECOG)
0	274 (80)
1	60 (18)
2	8 (2)
Body mass index, mean ± SD (range)	24.9 ± 4.0 (14.8-39.5)
Normoweight	200 (58)
Overweight	106 (31)
Obese	36 (11)
Type 2 diabetes	79 (23)
Impaired glucose tolerance	23 (7)

IQR: Interquartile range; ECOG: Eastern Cooperative Oncology Group.

Table 2 Glycemic indexes in gastrointestinal cancer patients - Comparison between patients who developed or not venous thromboembolism during chemotherapy

	Whole cohort	Venous thromboembolism		P value1
		Yes (n = 34)	No (n = 308)
Glycemia (mg/dL), mean ± SD (range)	107 ± 38 (51-415)	122 ± 53 (60-339)	105 ± 36 (51-415)	0.019
Insulinemia (μIU/mL), median (IQR)	12.5 (8.8-20.1)	17.2 (11.9-24.5)	11.6 (8.7-18.6)	0.016
HOMA index, median (IQR)	3.0 (2.0-5.6)	4.8 (3.0-8.1)	2.8 (2.0-4.9)	0.006
HbA1c (%), mean ± SD (range)	6.1 ± 0.8 (4.3-13.0)	6.2 ± 0.6 (5.2-8.0)	6.1 ± 0.8 (4.3-13.0)	0.436

¹Student t-test or Mann-Whitney U test were used for normally distributed or non parametric variables, respectively. IQR: Interquartile range.

Table 3 Receiver operating characteristics and Bayesian analysis of venous thromboembolism predictive value of glycemic parameters

	Fasting blood glucose	Fasting insulin	HOMA	HbA1c
AUC (SE)	0.636 (0.06)	0.630 (0.05)	0.647 (0.05)	0.574 (0.06)
95%CI	0.582-0.687	0.576-0.681	0.593-0.697	0.519-0.627
Criterion1	103 mg/dL	12 μIU/mL	2.6	6.0%
Sensitivity	75%	75%	81%	59%
Specificity	65%	51%	48%	63%
PPV	18%	14%	14%	14%
NPV	96%	95%	96%	94%
+LR (CI)	2.12 (1.54-2.57)	1.54 (1.13-1.85)	1.56 (1.19-1.81)	1.60 (1.07-2.13)
-LR (CI)	0.39 (0.19-0.68)	0.49 (0.23-0.87)	0. 39 (0.16-0.78)	0.65 (0.38-0.96)
P value2	0.0135	0.0128	0.0045	0.1989

¹Corresponding with highest Youden index;

²Significance level P (Area = 0.5). AUC: Area under the curve; PPV: Positive predictive value; NPV: Negative predictive value; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio.

Table 4 Cox proportional hazards survival regression analysis of the predictive value of clinical-pathological variables and glycemic indexes on venous thromboembolism-free survival of gastrointestinal cancer patients n (%)

Variable	n	VTE		HR (CI)	P value
		Yes	No
Sex
Male	197	17 (9)	180 (91)
Female	145	17 (12)	128 (88)	0.48 (0.24-0.97)	0.040
Age
≤ 65 yr	157	9 (6)	148 (94)
> 65 yr	185	25 (14)	160 (86)	2.15 (0.96-4.79)	0.062
Diabetes
No	240	20 (8)	220 (92)
IGT	23	2 (9)	21 (91)
T2D	79	12 (15)	67 (85)	0.94 (0.62-1.41)	0.748
Tumor site
Colorectal	237	25 (11)	212 (89)
Stomach	38	3 (8)	35 (92)
Esophagus	15	2 (13)	13 (87)
Pancreas	36	3 (8)	33 (92)
Biliary tract	16	1 (6)	15 (94)	0.78 (0.53-1.14)	0.201
Khorana class of risk
Low	199	19 (10)	180 (90)
Intermediate	118	13 (11)	105 (89)
High	25	2 (8)	23 (92)	1.20 (0.64-2.26)	0.562
Stage of disease
Primary	142	9 (6)	133 (94)
Metastatic	200	25 (12)	175 (88)	1.81 (0.75-4.33)	0.186
ECOG-PS
0	274	24 (9)	250 (91)
1	60	7 (12)	53 (88)
2	8	3 (37)	5 (62)	2.47 (1.22-4.99)	0.012
Homa index
≤ 2.6%	155	7 (5)	148 (95)
> 2.6%	187	27 (14)	160 (86)	4.13 (1.63-10.5)	0.003
Bevacizumab
No	270	22 (8)	248 (92)
Yes	72	12 (17)	60 (83)	1.77 (0.74-4.25)	0.199

ECOG-PS: Eastern Cooperative Oncology Group performance status; T2D: Type 2 diabetes; IGT: Impaired glucose tolerance; VTE: Venous thromboembolism.