Predictive value of immunotherapy-induced inflammation indexes: dynamic changes in patients with nasopharyngeal carcinoma receiving immune checkpoint inhibitors

Figures & data

Figure 1. Survival curves according to the cutoff levels of baseline SII, NLR, PLR, LCR, and LMR determined by X-tile.

(A) Significant difference in PFS between patients with baseline SII higher than 947.82 and those with SII lower than 947.82 (6.27 months vs 11.43 months, P < 0.001) in the training cohort.

(B) Significant difference in PFS between patients with baseline NLR lower than 3.17 and those with NLR higher than 3.17 (11.43 months vs 6.3 months, P = 0.0014) in the training cohort.

(C) Significant difference in PFS between patients with baseline PLR lower than 253.52 and those with PLR higher than 253.52 (9.5 months vs 6.1 months, P = 0.0335) in the training cohort.

(D) Significant difference in PFS between patients with baseline LCR higher than 0.03 and those with LCR lower than 0.03 (9.6 months vs 3.95 months, P = 0.0009) in the training cohort.

(E) Significant difference in PFS between patients with baseline LMR higher than 1.34 and those with LMR lower than 1.34 (9.4 months vs 1.78 months, P < 0.001) in the training cohort.

(F) Significant difference in PFS between patients with baseline SII higher than 947.82 and those with SII lower than 947.82 (8.17 months vs 17.9 months, P = 0.0423) in the validation cohort.

(G) Significant difference in PFS between patients with baseline NLR lower than 3.17 and those with NLR higher than 3.17 (17.9 months vs 12.6 months, P = 0.016) in the validation cohort.

(H) Significant difference in PFS between patients with baseline PLR lower than 253.52 and those with PLR higher than 253.52 (16.97 months vs 10.67 months, P = 0.0476) in the validation cohort.

(I) Significant difference in PFS between patients with baseline LCR higher than 0.03 and those with LCR lower than 0.03 (17 months vs 8.17 months, P = 0.0456) in the validation cohort.

(J) Significant difference in PFS between patients with baseline LMR higher than 1.34 and those with LMR lower than 1.34 (17.73 months vs 8.17 months, P = 0.0178) in the validation cohort.

Figure 2. Survival curves according to fluctuations in SII, NLR, and LMR levels.

(A) Significant difference in SII between patients with SII elevation and those with SII reduction after receiving immunotherapy compared to the baseline (7.13 months vs 11.27 months, P = 0.0416) in the training cohort.

(B) Significant difference in NLR between patients with NLR elevation and those with NLR reduction after receiving immunotherapy compared to the baseline (6.93 months vs 11.07 months, P = 0.0412) in the training cohort.

(C) Significant difference in LMR between patients with LMR elevation and those with LMR reduction after receiving immunotherapy compared to the baseline (13.3 months vs 7.1 months, P = 0.0128) in the training cohort.

(D) Significant difference in SII between patients with SII elevation and those with SII reduction after receiving immunotherapy compared to the baseline (12.63 months vs 23.5 months, P = 0.0435) in the validation cohort.

(E) Significant difference in NLR between patients with NLR elevation and those with NLR reduction after receiving immunotherapy compared to the baseline (12.6 months vs 17 months, P = 0.0399) in the validation cohort.

(F) Significant difference in LMR between patients with LMR elevation and those with LMR reduction after receiving immunotherapy compared to the baseline (17.73 months vs 8.77 months, P = 0.005) in the validation cohort.

Table 2. Predictive factors for PFS by univariate analysis.

	Training cohort	Validation cohort
	HR (95% CI)	P value	HR (95% CI)	P value
Gender
Female	1.000 (ref.)		1.000(ref.)
Male	0.822 (0.539-1.252)	0.361	1.239 (0.779-1.970)	0.366
Age
≥60	1.000 (ref.)		1.000 (ref.)
<60	0.850 (0.498-1.450)	0.551	0.975 (0.615-1.545)	0.913
EBV status
Negative	1.000 (ref.)		1.000 (ref.)
Positive	1.765 (1.227-2.538)	0.002	2.046 (1.285-3.269)	0.003
Histological
III	1.000 (ref.)		1.000 (ref.)
I-II	1.272 (0.933-1.733)	0.129	1.165 (0.874-1.553)	0.299
Family history
Yes	1.000 (ref.)		1.000 (ref.)
No	1.117 (0.712-1.754)	0.630	0.876 (0.464-1.654)	0.683
Smoking status
Smokers	1.000 (ref.)		1.000 (ref.)
Non-smokers	0.971 (0.697-1.352)	0.860	1.262 (0.797-1.999)	0.320
T-stage
T3-4	1.000 (ref.)		1.000 (ref.)
T1-2	0.738 (0.533-1.023)	0.068	1.507(0.949-2.391)	0.082
N-stage
N2-3	1.000 (ref.)		1.000 (ref.)
N0-1	0.915 (0.649-1.290)	0.612	1.150 (0.742-1.782)	0.532
M-stage
M1	1.000 (ref.)		1.000 (ref.)
M0	1.040 (0.757-1.429)	0.809	1.239 (0.779-1.970)	0.366
Disease stage
III-IV	1.000 (ref.)		1.000 (ref.)
I-II	0.760 (0.549-1.052)	0.098	1.514 (0.975-2.351)	0.065
Radiotherapy
Radiotherapy	1.000 (ref.)		1.000 (ref.)
Non-radiotherapy	0.884 (0.621-1.259)	0.496	1.181(0.609-2.290)	0.623
Baseline SII
Low	1.000 (ref.)		1.000 (ref.)
High	1.938 (1.412-2.660)	<0.001	1.562 (1.012-2.413)	0.0423
Baseline NLR
Low	1.000 (ref.)		1.000 (ref.)
High	1.604 (1.157-2.223)	0.0014	1.699 (1.098-2.630)	0.0160
Baseline PLR
Low	1.000 (ref.)		1.000 (ref.)
High	1.374 (0.997-1.893)	0.0335	1.679 (0.999-2.822)	0.0476
Baseline LCR
Low	1.000 (ref.)		1.000 (ref.)
High	0.529 (0.361-0.776)	0.0009	0.626 (0.394-0.996)	0.0456
Baseline LMR
Low	1.000 (ref.)		1.000 (ref.)
High	0.152 (0.092-0.250)	<0.001	0.510 (0.289-0.899)	0.0178
SII
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	1.340 (0.981-1.830)	0.0416	1.608 (1.028-2.517)	0.0435
NLR
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	1.353 (0.993-1.844)	0.0412	1.556 (1.017-2.382)	0.0399
PLR
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	1.000 (0.734-1.363)	0.8741	0.659 (0.427-1.019)	0.0585
LCR
Reduction	1.000 (ref.)		1.000(ref.)
Elevation	0.937 (0.680-1.290)	0.8105	1.488 (0.973-2.275)	0.0645
LMR
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	0.620 (0.450-0.855)	0.0128	0.433 (0.276-0.679)	0.005

Abbreviations: PFS, Progression-free survival; HR, Hazard ratio; CI, Confidence interval. SII, systemic immune-inflammation index; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LCR, lymphocyte-to-C-reactive protein ratio; LMR, lymphocyte-monocyte ratio.

Table 3. Predictive factors for PFS by multivariate analysis.

	Training cohort	Validation cohort
	HR (95% CI)	P value	HR (95% CI)	P value
EBV status
Negative	1.000 (ref.)		1.000 (ref.)
Positive	1.814 (1.223-2.690)	0.003	1.808 (1.057-3.093)	0.031
Histological
I-II	1.000 (ref.)		1.000 (ref.)
III	1.050 (0.718-)	0.801	1.081 (0.790-1.479)	0.628
T-stage
T3-4	1.000 (ref.)		1.000 (ref.)
T1-2	0.754 (0.508-1.119)	0.162	1.225 (0.731-2.053)	0.441
Disease Stage
III-IV	1.000 (ref.)		1.000 (ref.)
I-II	0.735 (0.509-1.063)	0.102	1.125 (0.511-2.483)	0.769
Baseline SII
Low	1.000 (ref.)		1.000 (ref.)
High	1.583 (1.110-2.259)	0.011	3.224 (1.614-6.437)	0.001
Baseline NLR
Low	1.000 (ref.)		1.000 (ref.)
High	1.258 (0.841-1.883)	0.263	1.358 (0.612-3.010)	0.452
Baseline PLR
Low	1.000 (ref.)		1.000 (ref.)
High	0.913 (0.601-1.386)	0.668	0.752 (0.318-1.777)	0.515
Baseline LCR
Low	1.000 (ref.)		1.000 (ref.)
High	0.735 (0.470-1.147)	0.175	1.930 (0.667-5.583)	0.225
Baseline LMR
Low	1.000 (ref.)		1.000 (ref.)
High	0.237 (0.135-0.416)	<0.001	0.392 (0.177-0.867)	0.021
SII
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	1.503 (1.081-2.090)	0.015	3.187 (1.770-5.738)	<0.001
NLR
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	1.240 (0.842-1.827)	0.277	0.960 (0.511-1.803)	0.898
LMR
Reduction	1.000 (ref.)		1.000 (ref.)
Elevation	0.646 (0.434-0.962)	0.031	0.350 (0.192-0.641)	0.001
PLR
Reduction			1.000 (ref.)
Elevation			0.654 (0.342-1.248)	0.197
LCR
Reduction			1.000(ref.)
Elevation			0.000 (0.000-1.015)	0.050

Abbreviations: PFS, Progression-free survival; HR, Hazard ratio; CI, Confidence interval; SII, systemic immune-inflammation index; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LCR, lymphocyte-to-C-reactive protein ratio; LMR, lymphocyte-monocyte ratio.

Table 1. The impact of baseline inflammation-related indications and dynamic changes for PFS.

Inflammation-related indications	Training cohort			Validation cohort
	N	PFS (months), median and range	P value	N	PFS (months), median and range	P value
Baseline SIIa			<0.001			0.0423
High	92	6.27 (1.07-47.4)		38	8.17 (0.87-69.03)
Low	92	11.43 (0.73-37.57)		62	17.9 (0.63-59.7)
Baseline NLR^a			0.0014			0.0160
High	117	6.3 (0.73-47.4)		39	12.6 (0.87-54.4)
Low	67	11.43 (2.03-33.37)		61	17.9 (0.63-69.03)
Baseline PLR^a			0.0335			0.0476
High	64	6.1 (1.03-47.4)		22	10.67 (0.87-30.5)
Low	120	9.5 (0.73-37.57)		78	16.97 (0.63-69.03)
Baseline LCR^a			0.0009			0.0456
High	150	9.6 (0.73-47.4)		70	17 (0.63-69.03)
Low	34	3.95 (0.77-28.2)		30	8.17 (0.87-54.4)
Baseline LMR^a			<0.001			0.0178
High	160	9.4 (0.87-47.4)		81	17.73 (0.87-69.03)
Low	24	1.78 (0.73-9.77)		19	8.17 (1.13-54.4)
SIIb			0.0416			0.0435
Elevation	101	7.13 (0.73-37.57)		68	12.63 (0.87-59.7)
Reduction	83	11.27 (1.17-47.4)		32	23.5 (5.17-69.03)
NLR^b			0.0412			0.0399
Elevation	89	6.93 (0.73-37.57)		55	12.6 (0.87-69.03)
Reduction	95	11.07 (0.83-47.4)		45	17 (1.13-59.7)
PLR^b			0.8741			0.0585
Elevation	82	9.4 (0.87-37.57)		64	17 (0.87-59.7)
Reduction	102	7.93 (0.73-47.4)		36	12.07 (0.9-69.03)
LCR^b			0.8105			0.0645
Elevation	67	9.8 (0.87-37.57)		54	12.6 (0.87-69.03)
Reduction	117	7.7 (0.73-47.4)		46	17 (1.13-59.7)
LMR^b			0.0128			0.005
Elevation	71	13.3 (1.03-47.4)		62	17.73 (0.87-69.03)
Reduction	113	7.1 (0.73-37.57)		38	8.77 (0.9-30.5)

Abbreviations: PFS, Progression-free survival; SII, systemic immune-inflammation index; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LCR, lymphocyte-to-C-reactive protein ratio; LMR, lymphocyte-monocyte ratio.

^a Comparison between baseline inflammation-related indications of high and low.

^b Comparison between inflammation-related indications post-immunotherapy and inflammation-related indications at pre-immunotherapy.

Data availability statement

The data generated and analyzed is available from the corresponding author upon reasonable request. The authenticity of this article has been validated with key raw data uploaded onto the Research Data Deposit (RDD) public platform (https://www.researchdata.org.cn). The approval RDD number is RDDA2023623285.