Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study

Table 1 Baseline characteristics of the study participants

Variables	Total, n = 500	Low-risk group, n = 194	Intermediate-risk group, n = 218	High-risk group, n = 88	P value
Age, median (IQR)	68.9 (62.5, 75.9)	69.1 (62.9, 75.2)	68.6 (62.6, 76.2)	69.0 (61.4, 76.8)	0.93
Sex, n (%)					0.459
Male	306 (61.2)	117 (60.3)	130 (59.6)	59 (67)
Female	194 (38.8)	77 (39.7)	88 (40.4)	29 (33)
CAT, n (%)					0.254
Non	430 (86.0)	161 (83)	190 (87.2)	79 (89.8)
All CAT	70 (14.0)	33 (17)	28 (12.8)	9 (10.2)
ATE	11 (2.2)	0 (0)	6 (2.8)	5 (5.7)
ECOG PS, n (%)					0.053
0-1	449 (89.8)	181 (93.3)	194 (89)	74 (84.1)
≥ 2	51 (10.2)	13 (6.7)	24 (11)	14 (15.9)
Cancer type, n (%)					< 0.001
GC	206 (41.2)	0 (0)	123 (56.4)	83 (94.3)
CRC	294 (58.8)	194 (100)	95 (43.6)	5 (5.7)
Adjuvant chemotherapy, n (%)					0.069
No	306 (61.2)	111 (57.2)	132 (60.6)	63 (71.6)
Yes	194 (38.8)	83 (42.8)	86 (39.4)	25 (28.4)
Active cancer (AC), n (%)					0.201
Non-AC	141 (28.2)	57 (29.4)	66 (30.3)	18 (20.5)
AC	359 (71.8)	137 (70.6)	152 (69.7)	70 (79.5)
Single or multiple primary tumor, n (%)					0.95
Single	450 (90.0)	174 (89.7)	196 (89.9)	80 (90.9)
Multiple	50 (10.0)	20 (10.3)	22 (10.1)	8 (9.1)
Pathological type, n (%)					< 0.001
Well and mod	317 (63.4)	169 (87.1)	120 (55)	28 (31.8)
Others	169 (33.8)	19 (9.8)	95 (43.6)	55 (62.5)
Unknown	14 (2.8)	6 (3.1)	3 (1.4)	5 (5.7)
Primary site surgery, n (%)					< 0.001
No	122 (24.4)	19 (9.8)	58 (26.6)	45 (51.1)
Yes	378 (75.6)	175 (90.2)	160 (73.4)	43 (48.9)
CVC placement, n (%)					< 0.001
No	168 (33.6)	46 (23.7)	89 (40.8)	33 (37.5)
Yes	332 (66.4)	148 (76.3)	129 (59.2)	55 (62.5)
Opportunity for Diagnosis, n (%)					0.714
Asymptomatic	495 (99.0)	193 (99.5)	215 (98.6)	87 (98.9)
Symptomatic	5 (1.0)	1 (0.5)	3 (1.4)	1 (1.1)
Thrombosis treatment, n (%)					0.424
No	470 (94.0)	179 (92.3)	207 (95)	84 (95.5)
Yes	30 (6.0)	15 (7.7)	11 (5)	4 (4.5)

CAT: Cancer associated thrombosis; ATE: Arterial thromboembolism; ECOG PS: Eastern Cooperative Oncology Group; GC: Gastric cancer; CRC: Colorectal cancer; AC: Active cancer; Well: Well-differentiated adenocarcinoma; Mod: Moderately differentiated adenocarcinoma; CVC: Central venous catheter; IQR: Interquartile range.

Table 2 Univariate analyses of all-cause death within 2 years

Variables	HR (95%CI)	P value
Age (≥ 65 yr vs < 65 yr)	1.22 (1.02-1.47)	0.034
KRS (intermediate vs low)	1.60 (1.21-2.13)	0.001
KRS (high vs low)	2.67 (1.91-3.73)	< 0.001
Sex (female vs male)	1.02 (0.79-1.30)	0.900
CAT (yes vs no)	1.01 (0.71-1.43)	0.965
ATE (yes vs no)	1.36 (0.60-3.05)	0.481
ECOG PS (≥ 2 vs 0-1)	4.05 (2.93-5.61)	< 0.001
Cancer type (CRC vs GC)	0.60 (0.47-0.76)	< 0.001
Pathological type (others vs well and mod)	1.53 (1.19-1.96)	< 0.001
Pathological type (unknown vs well and mod)	1.45 (0.68-3.09)	0.338
Primary site surgery (yes vs no)	0.30 (0.23-0.39)	< 0.001
Adjuvant chemotherapy (yes vs no)	0.28 (0.21-0.38)	< 0.001
Active cancer (yes vs no)	4.28 (2.94-6.24)	< 0.001
Multiple primary vs single primary	0.94 (0.62-1.44)	0.784
CVC placement (yes vs no)	1.92 (1.44-2.55)	< 0.001
Thrombosis treatment (yes vs no)	0.92 (0.56-1.53)	0.761
Opportunity for diagnosis (symptomatic vs asymptomatic)	1.57 (0.50-4.91)	0.436

KRS: Khorana risk score; CAT: Cancer associated thrombosis; ATE: Arterial thromboembolism; ECOG PS: Eastern Cooperative Oncology Group; GC: Gastric cancer; CRC: Colorectal cancer; Well: Well-differentiated adenocarcinoma; Mod: Moderately differentiated adenocarcinoma; CVC: Central venous catheter; HR: Hazard ratios; CI: Confidence intervals.

Table 3 Multivariate analysis of the association between Khorana risk score and all-cause death within 2 years

Variable	Crude mode		Multivariable-adjusted model 1		Multivariable-adjusted model 2		Multivariable-adjusted model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Trend test1	1.63 (1.38-1.93)	< 0.001	1.62 (1.37-1.92)	< 0.001	1.39 (1.10-1.76)	0.005	1.42 (1.12-1.8)	0.004
KRS, low-risk group	1 (Ref)		1 (Ref)		1 (Ref)		1 (Ref)
KRS, intermediate-risk group	1.6 (1.21-2.13)	0.001	1.6 (1.20-2.12)	0.001	1.43 (1.00-2.04)	0.047	1.45 (1.02-2.06)	0.041
KRS, high-risk group	2.67 (1.91-3.73)	< 0.001	2.64 (1.89-3.69)	< 0.001	1.95 (1.22-3.12)	0.005	2.02 (1.26-3.24)	0.004

¹A test for linear trend was performed for each model.

Multivariable-adjusted model 1: Adjusted for age and sex; Multivariable-adjusted model 2: Adjusted for age, sex, cancer-associated thrombosis (CAT), Eastern Cooperative Oncology Group (ECOG PS), cancer type, primary site surgery, adjuvant chemotherapy, active cancer and central venous catheter (CVC); Multivariable-adjusted model 3: Adjusted for age, sex, CAT, ECOG PS, cancer type, pathological type, primary site surgery, adjuvant chemotherapy, active cancer, single or multiple primary, CVC, thrombosis treatment, opportunity for diagnosis. KRS: Khorana risk score; HR: Hazard ratios; CI: Confidence intervals.