Preoperative immunonutrition status predicts survival after colorectal cancer resection: Nomogram based on modified systemic inflammation score

Table 1 Baseline demographic and clinicopathological characteristics of patients in the training and validation cohorts, n (%)

Characteristic	Cohort			P value
	Overall (n = 489)	Training cohort (n = 293)	Validation cohort (n = 196)
Gender				0.554
Female	205 (41.9)	126 (43.0)	79 (40.3)
Male	284 (58.1)	167 (57.0)	117 (59.7)
Age				0.058
< 45	48 (9.8)	36 (12.3)	12 (6.1)
> 60	259 (53.0)	155 (52.9)	104 (53.1)
45-60	182 (37.2)	102 (34.8)	80 (40.8)
BMI				0.661
< 18.5	16 (3.3)	11 (3.8)	5 (2.6)
> 28	59 (12.1)	33 (11.3)	26 (13.3)
18.5-24	211 (43.1)	131 (44.7)	80 (40.8)
24-28	203 (41.5)	118 (40.3)	85 (43.4)
Smoking				0.487
No	338 (69.1)	206 (70.3)	132 (67.3)
Yes	151 (30.9)	87 (29.7)	64 (32.7)
Drink				0.026
No	400 (81.8)	249 (85.0)	151 (77.0)
Yes	89 (18.2)	44 (15.0)	45 (23.0)
T stage				0.483
T1-2	102 (20.9)	58 (19.8)	44 (22.4)
T3	346 (70.8)	213 (72.7)	133 (67.9)
T4	41 (8.4)	22 (7.5)	19 (9.7)
N stage				0.634
N0	301 (61.6)	176 (60.1)	125 (63.8)
N1	115 (23.5)	70 (23.9)	45 (23.0)
N2	73 (14.9)	47 (16.0)	26 (13.3)
Tumor stage				0.477
I	88 (18.0)	48 (16.4)	40 (20.4)
II	213 (43.6)	128 (43.7)	85 (43.4)
III	188 (38.4)	117 (39.9)	71 (36.2)
Differentiated degree				0.499
Well	25 (5.1)	15 (5.1)	10 (5.1)
Moderately	334 (68.3)	194 (66.2)	140 (71.4)
Poorly	87 (17.8)	54 (18.4)	33 (16.8)
Undifferentiated	43 (8.8)	30 (10.2)	13 (6.6)
Nerve invasion				0.780
No	407 (83.2)	245 (83.6)	162 (82.7)
Yes	82 (16.8)	48 (16.4)	34 (17.3)
Intravascular tumor emboli				0.063
No	401 (82.0)	248 (84.6)	153 (78.1)
Yes	88 (18.0)	45 (15.4)	43 (21.9)
CEA				0.721
High	175 (35.8)	103 (35.2)	72 (36.7)
Normal	314 (64.2)	190 (64.8)	124 (63.3)
CA19-9				0.413
High	53 (10.8)	29 (9.9)	24 (12.2)
Normal	436 (89.2)	264 (90.1)	172 (87.8)

P values were calculated using Pearson’s χ² test or Fisher’s exact test, as appropriate. BMI: Body mass index; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 2 Baseline demographic and clinicopathological characteristics stratified by serum albumin and neutrophil-to-lymphocyte ratio in the training cohort, n (%)

Characteristic	Albumin			P value	NLR			P value
	Overall (n = 293)	< 38.95 (n = 103)	≥ 38.95 (n = 190)		Overall (n = 293)	< 2.96 (n = 229)	≥ 2.96 (n = 64)
Gender				0.942				0.314
Female	126 (43.0)	44 (42.7)	82 (43.2)		126 (43.0)	102 (44.5)	24 (37.5)
Male	167 (57.0)	59 (57.3)	108 (56.8)		167 (57.0)	127 (55.5)	40 (62.5)
Age				0.008				0.757
< 45	36 (12.3)	8 (7.8)	28 (14.7)		36 (12.3)	27 (11.8)	9 (14.1)
> 60	155 (52.9)	67 (65.0)	88 (46.3)		155 (52.9)	120 (52.4)	35 (54.7)
45-60	102 (34.8)	28 (27.2)	74 (38.9)		102 (34.8)	82 (35.8)	20 (31.3)
BMI				0.102				0.120
< 18.5	11 (3.8)	7 (6.8)	4 (2.1)		11 (3.8)	6 (2.6)	5 (7.8)
> 28	33 (11.3)	14 (13.6)	19 (10.0)		33 (11.3)	26 (11.4)	7 (10.9)
18.5-24	131 (44.7)	47 (45.6)	84 (44.2)		131 (44.7)	99 (43.2)	32 (50.0)
24-28	118 (40.3)	35 (34.0)	83 (43.7)		118 (40.3)	98 (42.8)	20 (31.3)
Smoking				0.876				0.537
No	206 (70.3)	73 (70.9)	133 (70.0)		206 (70.3)	163 (71.2)	43 (67.2)
Yes	87 (29.7)	30 (29.1)	57 (30.0)		87 (29.7)	66 (28.8)	21 (32.8)
Drink				0.061				0.344
No	249 (85.0)	93 (90.3)	156 (82.1)		249 (85.0)	197 (86.0)	52 (81.3)
Yes	44 (15.0)	10 (9.7)	34 (17.9)		44 (15.0)	32 (14.0)	12 (18.8)
T stage				0.004				0.033
T1-2	58 (19.8)	12 (11.7)	46 (24.2)		58 (19.8)	52 (22.7)	6 (9.4)
T3	213 (72.7)	78 (75.7)	135 (71.1)		213 (72.7)	162 (70.7)	51 (79.7)
T4	22 (7.5)	13 (12.6)	9 (4.7)		22 (7.5)	15 (6.6)	7 (10.9)
N stage				0.743				0.506
N0	176 (60.1)	61 (59.2)	115 (60.5)		176 (60.1)	136 (59.4)	40 (62.5)
N1	70 (23.9)	27 (26.2)	43 (22.6)		70 (23.9)	58 (25.3)	12 (18.8)
N2	47 (16.0)	15 (14.6)	32 (16.8)		47 (16.0)	35 (15.3)	12 (18.8)
Tumor stage				0.061				0.048
I	48 (16.4)	10 (9.7)	38 (20.0)		48 (16.4)	43 (18.8)	5 (7.8)
II	128 (43.7)	51 (49.5)	77 (40.5)		128 (43.7)	93 (40.6)	35 (54.7)
III	117 (39.9)	42 (40.8)	75 (39.5)		117 (39.9)	93 (40.6)	24 (37.5)
Differentiated degree				0.248				0.707
Well	15 (5.1)	7 (6.8)	8 (4.2)		15 (5.1)	11 (4.8)	4 (6.3)
Moderately	194 (66.2)	66 (64.1)	128 (67.4)		194 (66.2)	155 (67.7)	39 (60.9)
Poorly	54 (18.4)	23 (22.3)	31 (16.3)		54 (18.4)	40 (17.5)	14 (21.9)
Undifferentiated	30 (10.2)	7 (6.8)	23 (12.1)		30 (10.2)	23 (10.0)	7 (10.9)
Nerve invasion				0.090				0.563
No	245 (83.6)	81 (78.6)	164 (86.3)		245 (83.6)	193 (84.3)	52 (81.3)
Yes	48 (16.4)	22 (21.4)	26 (13.7)		48 (16.4)	36 (15.7)	12 (18.8)
Intravascular tumor emboli				0.951				0.214
No	248 (84.6)	87 (84.5)	161 (84.7)		248 (84.6)	197 (86.0)	51 (79.7)
Yes	45 (15.4)	16 (15.5)	29 (15.3)		45 (15.4)	32 (14.0)	13 (20.3)
CEA				0.046				0.459
High	103 (35.2)	44 (42.7)	59 (31.1)		103 (35.2)	78 (34.1)	25 (39.1)
Normal	190 (64.8)	59 (57.3)	131 (68.9)		190 (64.8)	151 (65.9)	39 (60.9)
CA19-9				0.049				0.527
High	29 (9.9)	15 (14.6)	14 (7.4)		29 (9.9)	24 (10.5)	5 (7.8)
Normal	264 (90.1)	88 (85.4)	176 (92.6)		264 (90.1)	205 (89.5)	59 (92.2)

P values were calculated using Pearson’s χ² test or Fisher’s exact test, as appropriate. BMI: Body mass index; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; NLR: Neutrophil-to-lymphocyte ratio.

Table 3 Scoring criteria of the modified systemic inflammation score based on neutrophil-to-lymphocyte ratio and serum albumin

mSIS	NLR	Albumin	Number
0	< 2.96	≥ 38.95	160
1	NLR ≥ 2.96 or albumin < 38.95		111
2	≥ 2.96	< 38.95	22

The modified systemic inflammation score was calculated based on preoperative serum albumin and neutrophil-to-lymphocyte ratio. Cut-off values for serum albumin and neutrophil-to-lymphocyte ratio were determined using receiver operating characteristic curve analysis in the training cohort. mSIS: Modified systemic inflammation score; NLR: Neutrophil-to-lymphocyte ratio.

Table 4 Harrell’s C-index for modified systemic inflammation score and comparator variables (full cohort, n = 489)

Variable	C-index	95%CI
mSIS	0.775	0.737-0.811
Albumin	0.696	0.657-0.738
NLR	0.659	0.621-0.701
SIRI	0.640	0.602-0.683
CA19-9	0.512	0.486-0.540

95% confidence interval estimated via 500-iteration bootstrap resampling. C-index: 0.5 = no discrimination; 1.0 = perfect discrimination. CA19-9: Carbohydrate antigen 19-9; SIRI: Systemic inflammation response index; mSIS: Modified systemic inflammation score; NLR: Neutrophil-to-lymphocyte ratio; CI: Confidence interval.

Table 5 Univariable and multivariable Cox proportional hazards regression analyses for overall survival in the training cohort, n (%)

Characteristic	Univariable					Multivariable
	n	Event number	HR	95%CI	P value	n	Event number	HR	95%CI	P value
Gender
Female	126	32				126	32
Male	167	46	1.11	0.70-1.74	0.660	167	46	0.97	0.49-1.93	0.930
Age
< 45	36	10				36	10
> 60	155	48	1.15	0.58-2.28	0.681	155	48	1.50	0.65-3.44	0.342
45-60	102	20	0.68	0.32-1.44	0.312	102	20	0.87	0.36-2.14	0.768
BMI
< 18.5	11	6				11	6
> 28	33	9	0.47	0.17-1.31	0.148	33	9	1.28	0.37-4.42	0.694
18.5-24	131	38	0.47	0.20-1.10	0.083	131	38	0.90	0.31-2.57	0.843
24-28	118	25	0.33	0.14-0.81	0.016	118	25	1.23	0.43-3.48	0.702
Smoking
No	206	57				206	57
Yes	87	21	0.81	0.49-1.34	0.420	87	21	0.85	0.36-2.03	0.718
Drink
No	249	71				249	71
Yes	44	7	0.50	0.23-1.09	0.083	44	7	0.61	0.20-1.81	0.370
T stage
T1-2	58	3				58	3
T3	213	62	6.49	2.04-20.67	0.002	213	62	2.57	0.31-21.45	0.384
T4	22	13	15.67	4.46-55.06	< 0.001	22	13	3.41	0.37-31.31	0.278
N stage
N0	176	34				176	34
N1	70	23	1.87	1.10-3.18	0.020	70	23	1.65	0.12-21.99	0.705
N2	47	21	2.92	1.70-5.04	< 0.001	47	21	2.48	0.20-30.82	0.480
Tumor stage
I	48	2				48	2
II	128	32	6.65	1.59-27.75	0.009	128	32	1.06	0.08-14.18	0.964
III	117	44	11.29	2.74-46.57	< 0.001	117	44
Differentiated degree
Well	15	2				15	2
Moderately	194	35	1.33	0.32-5.54	0.692	194	35	1.59	0.35-7.24	0.546
Poorly	54	33	6.54	1.57-27.29	0.010	54	33	5.38	1.16-25.06	0.032
Undifferentiated	30	8	2.19	0.46-10.30	0.322	30	8	2.91	0.57-14.95	0.201
Nerve invasion
No	245	53				245	53
Yes	48	25	3.23	2.00-5.20	< 0.001	48	25	2.15	1.08-4.28	0.052
Intravascular tumor emboli
No	248	58				248	58
Yes	45	20	2.29	1.38-3.81	0.001	45	20	1.16	0.57-2.39	0.684
CEA
High	103	35				103	35
Normal	190	43	0.62	0.40-0.97	0.036	190	43	1.18	0.68-2.03	0.560
CA19-9
High	29	15				29	15
Normal	264	63	0.34	0.19-0.59	< 0.001	264	63	0.39	0.19-0.80	0.010
Albumin
< 38.95	103	56				103	56
≥ 38.95	190	22	0.16	0.10-0.27	< 0.001	190	22	0.46	0.23-0.93	0.03
NLR
< 2.96	229	41				229	41
≥ 2.96	64	37	4.25	2.72-6.65	< 0.001	64	37	1.26	1.10-1.40	< 0.001
mSIS
0	155	10				155	10
1-2	138	68	9.92	5.10-19.29	< 0.001	138	68	4.06	2.10-7.85	< 0.001
PLR
< 157.70	193	34				193	34
≥ 157.70	100	44	2.91	1.86-4.55	< 0.001	100	44	1.40	0.79-2.49	0.249
LMR
< 2.88	71	36				71	36
≥ 2.88	222	42	0.30	0.19-0.47	< 0.001	222	42	1.64	0.71-3.80	0.247
SIRI
< 1.71	244	46				244	46
≥ 1.71	49	32	5.13	3.26-8.08	< 0.001	49	32	4.70	1.77-12.44	0.002

Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression models. For categorical variables, the first category listed was used as the reference. P < 0.05 was considered statistically significant. CI: Confidence interval; HR: Hazard ratio; BMI: Body mass index; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; mSIS: Modified systemic inflammation score; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; SIRI: Systemic inflammation response index.