Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas

Xianchun Gao; Yanan Pan; Weili Han; Caie Hu; Chenchen Wang; Ling Chen; Yong Guo; Yupeng Shi; Yan Pan; Huahong Xie; Liping Yao; Jianjun Yang; Jianyong Zheng; Xiaohua Li; Xiaonan Liu; Liu Hong; Jipeng Li; Mengbin Li; Gang Ji; Zengshan Li; Jielai Xia; Qingchuan Zhao; Daiming Fan; Kaichun Wu; Yongzhan Nie

doi:10.20892/j.issn.2095-3941.2020.0246

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Figure 1
Kaplan-Meier survival curves according to the neutrophil-to-lymphocyte ratio (NLR) and body mass index (BMI) at diagnosis in resectable gastric cancer patients. (A) Overall survival according to NLR in 2,542 patients. (B) Recurrence-free survival according to NLR in 2,542 patients. (C) Overall survival according to BMI in 2,542 patients. (D) Recurrence-free survival according to BMI in 2,542 patients. (E) Overall survival according to NLR and BMI in 2,542 patients. (F) Recurrence-free survival according to NLR and BMI in 2,542 patients. ^aNeither, indicating NLR < 3 and BMI ≥ 18.5 kg/m²; ^bboth, indicating NLR ≥ 3 and underweight (BMI < 18.5 kg/m²).

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Table 1

Baseline characteristics according to the neutrophil-to-lymphocyte ratio and body mass index at diagnosis

Characteristics	All patients (n = 2,542)	Neither^a (n = 1,664)	Only NLR ≥ 3 (n = 529)	Only BMI < 18.5 (n = 251)	Both^b (n = 98)	P
Age (years)						< 0.001
≥ 65	696 (27%)	408 (25%)	166 (31%)	84 (34%)	38 (39%)
55 to < 65	930 (37%)	603 (36%)	200 (38%)	94 (38%)	33 (34%)
< 55	916 (36%)	653 (39%)	163 (31%)	73 (29%)	27 (28%)
Gender						< 0.001
Male	1962 (77%)	1313 (79%)	421 (80%)	165 (66%)	63 (64%)
Female	580 (23%)	351 (21%)	108 (20%)	86 (34%)	35 (36%)
CCS, mean (SD)	0.16 (0.44)	0.15 (0.42)	0.22 (0.52)	0.13 (0.40)	0.14 (0.41)	0.012
Smoke						0.006
No	1633 (64%)	1036 (62%)	348 (66%)	184 (73%)	65 (66%)
Yes	909 (36%)	628 (38%)	181 (34%)	67 (27%)	33 (34%)
Alcohol						0.220
No	2228 (88%)	1448 (87%)	463 (88%)	230 (92%)	87 (89%)
Yes	314 (12%)	216 (13%)	66 (13%)	21 (8%)	11 (11%)
Family history of gastric cancer						0.685
No	2383 (94%)	1557 (94%)	494 (93%)	238 (95%)	94 (96%)
Yes	159 (6%)	107 (6%)	35 (7%)	13 (5%)	4 (4%)
Primary tumor location						0.002
Proximal	776 (31%)	505 (30%)	192 (36%)	60 (24%)	19 (19%)
Body	610 (24%)	395 (24%)	126 (24%)	64 (26%)	25 (26%)
Antrum	1156 (46%)	764 (46%)	211 (40%)	127 (51%)	54 (55%)
Type of gastrectomy						< 0.001
Proximal	262 (10%)	185 (11%)	53 (10%)	19 (8%)	5 (5%)
Total	1190 (47%)	744 (45%)	291 (55%)	109 (43%)	46 (47%)
Distal	1090 (43%)	735 (44%)	185 (35%)	123 (49%)	47 (48%)
Pathologic TNM stage^c						< 0.001
Stage I	660 (26%)	476 (29%)	107 (20%)	66 (26%)	11 (11%)
Stage II	651 (26%)	429 (26%)	136 (26%)	56 (22%)	30 (31%)
Stage III	1231 (48%)	759 (46%)	286 (54%)	129 (51%)	57 (58%)
T stage						< 0.001
T1	494 (19%)	365 (22%)	80 (15%)	42 (17%)	7 (7%)
T2	396 (16%)	270 (16%)	67 (13%)	45 (18%)	14 (14%)
T3	467 (18%)	299 (18%)	112 (21%)	33 (13%)	23 (24%)
T4	1185 (47%)	730 (44%)	270 (51%)	131 (52%)	54 (55%)
N stage						0.012
N0	981 (39%)	670 (40%)	184 (35%)	101 (40%)	26 (27%)
N1	472 (19%)	315 (19%)	99 (19%)	39 (16%)	19 (19%)
N2	450 (18%)	297 (18%)	94 (18%)	43 (17%)	16 (16%)
N3	639 (25%)	382 (23%)	152 (29%)	68 (27%)	37 (38%)
No. of lymph nodes dissected						0.014
≥16	2152 (85%)	1383 (83%)	458 (87%)	221 (88%)	90 (92%)
<16	390 (15%)	281 (17%)	71 (13%)	30 (12%)	8 (8%)
Histopathological differentiation						0.153
High/middle	989 (39%)	666 (40%)	199 (38%)	92 (37%)	32 (33%)
Poor	1443 (57%)	934 (56%)	305 (58%)	141 (56%)	63 (64%)
Signet ring cell or Mucinous	110 (4%)	64 (4%)	25 (5%)	18 (7%)	3 (3%)
Serum albumin (g/l)						< 0.001
≥40	1878 (74%)	1293 (78%)	376 (71%)	157 (63%)	52 (53%)
<40	664 (26%)	371 (22%)	153 (29%)	94 (38%)	46 (47%)
Anaemia						< 0.001
No	1883 (74%)	1321 (79%)	335 (63%)	174 (69%)	53 (54%)
Yes	659 (26%)	343 (21%)	194 (37%)	77 (31%)	45 (46%)
Surgical complications^d						0.913
No	2090 (82%)	1369 (82%)	437 (83%)	206 (82%)	78 (80%)
Yes	452 (18%)	295 (18%)	92 (17%)	45 (18%)	20 (20%)
30-day mortality						0.076
No	2521 (99.2%)	1654 (99.4%)	521 (98.5%)	250 (99.6%)	96 (98.0%)
Yes	21 (0.8%)	10 (0.6%)	8 (1.5%)	1 (0.4%)	2 (2.0%)
Treatment arm						0.193
Surgery only	853 (34%)	554 (33%)	169 (32%)	99 (39%)	31 (32%)
Surgery + chemotherapy	1689 (66%)	1110 (67%)	360 (68%)	152 (61%)	67 (68%)

^aIndicating NLR < 3 and BMI ≥ 18.5 kg/m²; ^bIndicating NLR ≥ 3 and underweight (BMI < 18.5 kg/m²); ^c8th UICC staging system; ^dDefined as grade II or higher using the Clavien-Dindo classification. NLR, neutrophil-to-lymphocyte ratio; BMI, body mass index; CCS, Charlson comorbidity score; SD, standard deviation; TNM, tumor-node-metastasis; T stage, tumor stage; N stage, node stage.

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Table 2

Mutually adjusted effects of neutrophil-to-lymphocyte ratio and body mass index and survival in 2,542 patients.

	Patients No.	Events No.	Univariable model HR (95% CI)	P value	Multivariable model 1^a HR (95% CI)	P	Multivariable model 2^b HR (95% CI)	P
Overall survival
NLR				< 0.001		< 0.001		0.004
≥3	627	279	1.497 (1.300–1.724)		1.280 (1.111–1.475)		1.236 (1.069–1.430)
<3	1915	639	1		1		1
BMI (kg/m²)				< 0.001		< 0.001		< 0.001
<18.5	349	176	1.722 (1.461–2.030)		1.607 (1.360–1.899)		1.600 (1.350–1.897)
≥18.5	2193	742	1		1		1
NLR and BMI (kg/m²)^c				< 0.001		< 0.001		< 0.001
Both^d	98	62	2.882 (2.213–3.752)		2.469 (1.891–3.225)		2.445 (1.853–3.225)
Neither^e	1664	525	1		1		1
Recurrence-free survival
NLR				< 0.001		< 0.001		0.008
≥3	627	246	1.447 (1.246–1.679)		1.257 (1.082–1.460)		1.230 (1.054–1.434)
<3	1915	584	1		1		1
BMI (kg/m²)				< 0.001		< 0.001		< 0.001
<18.5	349	165	1.804 (1.521–2.140)		1.672 (1.407–1.988)		1.658 (1.389–1.979)
≥18.5	2193	665	1		1		1
NLR and BMI (kg/m²)^c				< 0.001		< 0.001		< 0.001
Both^d	98	57	2.821 (2.142–3.715)		2.404 (1.818–3.177)		2.405 (1.802–3.209)
Neither^e	1664	476	1		1		1

^aAge, sex, adjuvant chemotherapy, and TNM stage were adjusted in multivariable model 1 for overall survival and recurrence-free survival; ^bAge, sex, adjuvant chemotherapy, primary tumor location, histopathological differentiation, number of lymph nodes dissected, TNM stage, family history of gastric cancer, Charlson comorbidity score, smoke, alcohol, anemia, hypoalbuminemia, type of gastrectomy and surgical complications were adjusted for a multivariable model 2 for overall survival and recurrence-free survival; ^cPatients were divided into 4 groups according to NLR and BMI: neither NLR ≥ 3 nor underweight (BMI < 18.5 kg/m²); NLR ≥ 3 only; underweight only; both NLR ≥ 3 and underweight; ^dIndicating NLR ≥ 3 and underweight (BMI < 18.5 kg/m²); ^eindicating NLR < 3 and BMI ≥ 18.5 kg/m². NLR, neutrophil-to-lymphocyte ratio; BMI, body mass index; HR, hazard ratio; CI, confidence intervals; TNM, tumor-node-metastasis.

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Table 3

Subgroup analysis for neutrophil-to-lymphocyte ratio and body mass index at diagnosis according to pathologic stage, age and adjuvant chemotherapy.

Stratification Variable	Overall Survival				Recurrence–free survival
Stratification Variable	Univariable model HR (95% CI)	P value	Multivariable model^a HR (95% CI)	P value	Univariable model HR (95% CI)	P value	Multivariable model^a HR (95% CI)	P value
NLR^b
Pathologic TNM stage
Stage I	1.666 (0.931–2.984)	0.086	1.705 (0.913–3.185)	0.094	0.817 (0.367–1.816)	0.619	0.985 (0.451–2.154)	0.970
Stage II	1.555 (1.124–2.150)	0.008	1.308 (0.929–1.842)	0.123	1.593 (1.128–2.249)	0.008	1.410 (0.980–2.031)	0.064
Stage III	1.246 (1.059–1.466)	0.008	1.186 (1.003–1.404)	0.047	1.245 (1.050–1.476)	0.012	1.190 (0.997–1.420)	0.054
Age at diagnosis, years
≥65	1.359 (1.075–1.719)	0.010	1.189 (0.927–1.525)	0.174	1.262 (0.972–1.640)	0.081	1.184 (0.898–1.560)	0.232
55 to <65	1.792 (1.428–2.248)	< 0.001	1.485 (1.175–1.876)	0.001	1.695 (1.337–2.148)	< 0.001	1.422 (1.113–1.816)	0.005
<55	1.175 (0.883–1.563)	0.269	1.036 (0.773–1.389)	0.812	1.251 (0.939–1.668)	0.126	1.113 (0.828–1.496)	0.477
Treatment arm
Surgery only	1.619 (1.273–2.060)	< 0.001	1.361 (1.058–1.750)	0.016	1.466 (1.116–1.926)	0.006	1.311 (0.989–1.738)	0.059
Surgery+chemotherapy	1.443 (1.213–1.716)	< 0.001	1.231 (1.028–1.473)	0.023	1.430 (1.196–1.709)	< 0.001	1.233 (1.025–1.484)	0.026
BMI^c
Pathologic TNM stage
Stage I	2.082 (1.130–3.839)	0.019	1.950 (1.037–3.666)	0.038	2.309 (1.183–4.504)	0.014	2.275 (1.155–4.482)	0.017
Stage II	1.693 (1.152–2.487)	0.007	1.811 (1.209–2.713)	0.004	1.743 (1.155–2.632)	0.008	1.859 (1.206–2.864)	0.005
Stage III	1.641 (1.357–1.986)	< 0.001	1.481 (1.215–1.806)	< 0.001	1.702 (1.399–2.070)	< 0.001	1.560 (1.272–1.913)	< 0.001
Age at diagnosis, years
≥65	1.699 (1.307–2.210)	< 0.001	2.029 (1.537–2.677)	< 0.001	1.785 (1.342–2.373)	< 0.001	2.155 (1.594–2.914)	< 0.001
55 to <65	1.537 (1.163–2.032)	0.003	1.344 (1.007–1.794)	0.045	1.708 (1.289–2.263)	< 0.001	1.535 (1.147–2.054)	0.004
<55	1.753 (1.265–2.430)	0.001	1.376 (0.973–1.946)	0.071	1.736 (1.243–2.424)	0.001	1.314 (0.923–1.871)	0.130
Treatment arm
Surgery only	1.762 (1.349–2.302)	< 0.001	1.490 (1.131–1.962)	0.005	1.899 (1.420–2.541)	< 0.001	1.611 (1.195–2.172)	0.002
Surgery+chemotherapy	1.691 (1.372–2.084)	< 0.001	1.684 (1.352–2.097)	< 0.001	1.758 (1.422–2.173)	< 0.001	1.697 (1.359–2.120)	< 0.001
NLR and BMI^d
Pathologic TNM stage
Stage I	4.972 (1.525–16.218)	0.008	5.419 (1.453–20.204)	0.012	1.683 (0.229–12.358)	0.609	1.998 (0.244–16.361)	0.519
Stage II	2.651 (1.512–4.647)	0.001	3.341 (1.826–6.112)	< 0.001	2.827 (1.573–5.079)	0.001	3.624 (1.912–6.869)	< 0.001
Stage III	2.385 (1.750–3.250)	< 0.001	2.189 (1.580–3.032)	< 0.001	2.387 (1.738–3.278)	< 0.001	2.183 (1.564–3.047)	< 0.001
Age at diagnosis, years
≥65	2.638 (1.752–3.973)	< 0.001	2.884 (1.836–4.529)	< 0.001	2.703 (1.746–4.183)	< 0.001	3.177 (1.950–5.178)	< 0.001
55 to <65	2.716 (1.692–4.359)	< 0.001	2.257 (1.358–3.750)	0.002	2.744 (1.687–4.463)	< 0.001	2.270 (1.347–3.824)	0.002
<55	2.773 (1.662–4.628)	< 0.001	2.381 (1.369–4.141)	0.002	2.573 (1.517–4.365)	< 0.001	2.066 (1.170–3.645)	0.012
Treatment arm
Surgery only	3.554 (2.274–5.555)	< 0.001	3.016 (1.837–4.949)	< 0.001	3.463 (2.112–5.678)	< 0.001	3.012 (1.752–5.176)	< 0.001
Surgery + chemotherapy	2.599 (1.873–3.607)	< 0.001	2.481 (1.754–3.511)	< 0.001	2.579 (1.85–3.595)	< 0.001	2.425 (1.706–3.449)	< 0.001

^aCox proportional hazards models adjusted for age, sex, adjuvant chemotherapy, primary tumor location, histopathological differentiation, number of lymph nodes dissected, TNM stage, family history of gastric cancer, Charlson comorbidity score, smoke, alcohol, anemia, hypoalbuminemia, type of gastrectomy and surgical complications, unless stratified by those variables; ^bAll HRs compared patients with NLR ≥ 3 vs. patients with NLR < 3; ^cAll HRs compared patients with underweight (BMI < 18.5 kg/m²) vs. patients with BMI ≥ 18.5 kg/m²; ^dAll HRs compared patients with NLR ≥ 3 and underweight vs. patients with NLR < 3 and BMI ≥ 18.5 kg/m². NLR, neutrophil-to-lymphocyte ratio; BMI, body mass index; HR, hazard ratio; CI, confidence intervals; TNM, tumor-node-metastasis.