Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

Table 1 Baseline characteristics

Variables	Number of patients, n = 271	%	Median (interquartile range)	CA19-9 positive, n = 219	%	CA19-9 negative, n = 52	%	P value1
Age (yr)			63 (57-70)
< 65	167	61.6		133	60.7	34	65.4	0.535
≥ 65	104	38.4		86	39.3	18	34.6
Sex
Male	178	65.7		147	67.1	31	59.6	0.305
Female	93	34.3		72	32.9	21	40.4
ECOG
0-1	216	79.7		171	78.1	45	86.5	0.173
≥ 2	55	20.3		48	21.9	7	13.5
Stage
Locally advanced	22	8.1		15	6.8	7	13.5	0.117
Metastatic	249	91.9		204	93.2	45	86.5
Differentiation
Well to moderately	177	65.3		142	64.8	35	67.3	0.262
Poorly	94	34.7		77	35.2	17	32.7
Biliary stent
Yes	30	11.1		28	12.8	2	3.8	0.084
No	241	88.9		191	87.2	50	96.2
Chemotherapy
Gemcitabine	86	31.7		72	32.9	14	26.9	0.967
Gemcitabine/Elrotinib	110	40.6		87	39.7	23	44.2
Gemcitabine/Nab-paclitaxel	39	14.4		31	14.2	8	15.4
Gemcitabine/Fluoropyrimidine	30	11.1		24	11.0	6	11.5
FOLFIRINOX	6	2.2		5	2.3	1	1.9
No. of metastatic sites
0-2	229	84.5		180	82.2	49	94.2	0.033
3-	42	15.5		39	17.8	3	5.8
Liver metastasis
Yes	122	45.0		106	48.4	16	30.8	0.022
No	149	55.0		113	51.6	36	69.2
Pretreatment NLR			2.66 (1.78-3.85)
< 2.60	130	48.0		97	44.3	33	63.5	0.013
≥ 2.60	141	52.0		122	55.7	19	36.5
Post-treatment NLR			2.53 (1.63-4.03)
< 2.62	143	52.8		106	48.4	37	71.2	0.003
≥ 2.62	128	47.2		113	51.6	15	28.8
CA19-9 (U/mL)			362.80 (64.98-1585.90)
≤ 37	52	19.2		0	0.0	52	100.0
> 37	219	80.8		219	100.0	0	0.0
CEA (ng/mL)			3.26 (2.00-7.95)
≤ 5	175	64.6		133	60.7	42	80.8	0.003
> 5	96	35.4		86	39.3	10	19.2

¹P value from Chi-square test or Fisher's exact test for categorical variables. ECOG PS: Eastern Cooperative Oncology Group Performance Status; NLR: Neutrophil-to-lymphocyte ratio; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; FOLFIRINOX: Folinic acid, 5-Fluorouracil, Irinotecan and Oxaliplatin.

Table 2 Univariate and multivariate analysis of overall survival, progression-free survival

	Overall survival						Progression-free survival
	Univariate			Multivariate			Univariate			Multivariate
	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
Age (yr)
< 65	1						1
≥ 65	1.08	0.84-1.39	0.557				0.97	0.75-1.24	0.786
Sex
Female	1						1
Male	1.12	0.86-1.46	0.406				1.08	0.83-1.39	0.573
ECOG
0-1	1			1			1
≥ 2	1.5	1.10-2.03	0.009	1.40	1.00-1.97	0.050	1.23	0.81-0.91	0.173
Stage
Locally advanced	1			1			1			1
Metastatic	1.84	1.13-2.98	0.014	2.17	1.28-3.69	0.004	1.95	1.23-3.09	0.005	1.91	1.16-3.15	0.011
Differentiation
Well to moderately	1			1			1
Poorly	1.35	1.04-1.74	0.026	1.48	1.11-1.96	0.007	1.06	0.82-1.36	0.662
Biliary stent
No	1						1
Yes	0.98	0.66-1.46	0.939				0.81	0.55-1.20	0.297
Liver metastasis
No	1			1			1			1
Yes	1.25	0.98-1.61	0.077	1.22	0.93-1.60	0.135	1.51	1.19-1.93	0.001	1.54	1.19-2.01	0.001
Chemotherapy
Gemcitabine single	1			1			1			1
Other regimens	0.68	0.52-0.89	0.004	0.70	0.53-0.93	0.015	0.78	0.60-1.01	0.062	0.86	0.65-1.14	0.303
Pretreatment NLR
< 2.60	1			1			1			1
≥ 2.60	1.77	1.37-2.29	< 0.001	1.09	0.81-1.48	0.545	1.61	1.26-2.07	< 0.001	1.03	0.78-1.36	0.816
Post-treatment NLR
< 2.62	1			1			1			1
≥ 2.62	2.42	1.87-3.14	< 0.001	2.47	1.84-3.32	< 0.001	2.51	1.93-3.26	< 0.001	2.59	1.94-3.47	< 0.001
CA19-9 reduction
< 18%	1			1			1			1
≥ 18%	0.53	0.41-0.69	< 0.001	0.51	0.39-0.67	< 0.001	0.54	0.46-0.75	< 0.001	0.6	0.47-0.78	< 0.001
CEA (ng/mL)
≤ 5	1			1			1			1
> 5	1.27	0.98-1.65	0.066	1.20	0.91-1.57	0.187	1.26	0.98-1.62	0.074	1.17	0.90-1.52	0.231

Univariate analysis and multivariate survival analysis were performed using Cox proportional hazard model, and P values < 0.05 were considered to indicate statistical significance. Significant values are in boldface type. CI: Confidence interval; HR: Hazard ratio; ECOG: Eastern Cooperative Oncology Group; NLR: Neutrophil-to-lymphocyte ratio; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 3 The association of the first response evaluation and post-treatment neutrophil-to-lymphocyte ratio according to carbohydrate antigen 19-9 response in carbohydrate antigen 19-9 positive group

	Decline of CA19-9 ≥ 18%					Decline of CA19-9 < 18%
Post-treatment NLR	< 2.62		≥ 2.62			< 2.62		≥ 2.62
	n = 67	%	n = 38	%	P value1	n = 39	%	n = 75	%	P value1
1st Response					0.002					0.009
CR/PR	35	52.2	10	26.3		4	10.3	5	6.7
SD	29	43.3	21	55.3		21	53.8	21	28.0
PD	3	4.5	7	18.4		14	35.9	49	65.3

¹P value from linear-by-linear association test. NLR: Neutrophil-to-lymphocyte ratio; CA19-9: Carbohydrate antigen 19-9; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 4 The association of the first response evaluation and post-treatment neutrophil-to-lymphocyte ratio in carbohydrate antigen 19-9 negative group

	CA19-9 negative group n = 52
Post-treatment NLR	< 2.62		≥ 2.62
	n = 37	%	n = 15	%	P value1
1st Response					0.032
CR/PR	8	21.6	3	20.0
SD	25	67.6	4	26.7
PD	4	10.8	8	53.3

¹P value from linear-by-linear association test. NLR: Neutrophil-to-lymphocyte ratio; CA19-9: Carbohydrate antigen 19-9; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.