Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis

Figures & data

Figure 1. Flow chart of the included studies.

Table 1. Characteristics of studies included in the meta-analysis.

Study	Year	Study period	Country	Sample size	Sex (F/M)	TNM stage	Treatment	Follow-up, median (range)	Cut-off value	Outcome	Analysis type	NOS	Ref.
Berardi et al.	2019	May 2006 – June 2015	Italy	311	95/216	III–IV	CT/T	NA	1270	OS/PFS	M/U	7	[9]
Bilgetekin and Basal	2020	Jan 2010 – Mar 2020	Turkey	123	27/96	NA	CT/T	14.36 (9.13–23.69)	730	OS/PFS	M	8	[10]
Coutu et al.	2022	2004 – 2019	USA	81	36/45	III	CRT+S	68.4	1260	OS/DFS	M	8	[11]
Delikgoz Soykut et al.	2022	Jan 2012 – Dec 2017	Turkey	392	29/363	IIIA–IIIB	CRT	NA	817	OS/PFS	M	8	[12]
Deng et al.	2019	Jan 2013 – Nov 2018	China	203	114/89	IV	T	NA	1343.665/1066.935	OS/PFS	M	6	[13]
Fu et al.	2021	Apr 2008 – Dec 2015	China	3984	1845/2139	I–IIIA	S	45.1	479	OS/RFS	M	8	[14]
Gao et al.	2018	Jan 2009 – Dec 2011	China	410	143/267	I–IIIA	S	NA	395.4	OS	M	7	[15]
Guo, D.	2018	Aug 2013 – Jan 2016	China	140	45/95	IIIB–IV	CRT/T	NA	521	OS/PFS	M	7	[16]
Guo, W.	2019	Jul 2006 – May 2012	China	569	144/425	I–III	S	60.3 (0.9–146.7)	419.6	OS	M	8	[17]
Ju et al.	2021	Jan 2014 – Dec 2016	China	102	61/41	IIIB–IV	T	NA	841.03	OS/PFS	M	8	[18]
Keit et al.	2021	2010 – 2019	USA	125	61/64	III	CRT	NA	1266	OS/PFS	M	7	[19]
Li, A. et al.	2020	Oct 2013 – Jan 2018	China	252	107/145	NA	Mixed	25.9 (1–63)	630.85	OS	M	7	[20]
Li, B. et al.	2019	Jun 2011 – Feb 2018	China	161	71/90	IIIB–IV	T	16.6 (2.3–86.3)	824	OS/PFS	U	7	[21]
Li, H. et al.	2019	May 2013 – May 2016	China	310	148/162	NA	Mixed	NA	1218.81	OS	M	6	[22]
Li, W. et al.	2021	Jan 2009 – Dec 2018	China	214	94/120	I–IV	R	61 (1–138)	696.52	OS	M	7	[23]
Li, X. et al.	2020	Dec 2012 – Dec 2018	China	345	90/255	IIIB–IV	RT/CRT	NA	555.59	OS	M	9	[24]
Liu et al.	2019	Mar 2016 – Jul 2018	China	44	11/33	IIIB–IV	T	6.9 (0.6–28.5)	603.5	OS/PFS	M	6	[25]
Shen et al.	2021	Jan 2014 – Dec 2015	China	1431	824/607	I	S	63 (1–82)	580.671	CSS/DFS	M	9	[26]
Takeda et al.	2021	Sep 2015 – Mar 2021	Japan	42	20/22	NA	T	NA	1000	PFS	U	6	[27]
Tomita et al.	2018	2008 – 2012	Japan	341	168/173	I–III	S	NA	471.2	CSS	U	7	[28]
Tong et al.	2017	Jan 2006 – May 2012	China	332	126/206	III	CT/CRT	NA	660	OS	M	7	[29]
Watanabe et al.	2021	2010 – 2019	Japan	387	154/233	I	S	39.2 (3–117)	715	RFS	M	8	[30]
Xu et al.	2021	Jan 2008 – May 2010	China	234	97/137	NA	CT/R	NA	618.3	OS	M	8	[31]
Yan et al.	2020	Jan 2009 – Dec 2011	China	538	195/343	I–IIIA	S	NA	402.37	OS/DFS	M	8	[32]
Zhang et al.	2021	May 2015 – Jun 2018	China	124	68/56	NA	RT	NA	480	OS/PFS	M	8	[33]

CRT: Chemoradiotherapy; CSS: Cancer-specific survival; CT: Chemotherapy; DFS: Disease-free survival; M: Multivariable; NA: Not available; NOS: Newcastle-Ottawa scale; OS: Overall survival; PFS: Progression-free survival; RFS: Recurrence-free survival; RT: Radiotherapy; S: Surgery; T: Targeted therapy; U: Univariable.

Figure 2. Forrest plots of studies evaluating hazard ratio with 95% CI of systemic immune inflammatory index for overall survival (A), progression-free survival (B) and disease-free survival (C).

Weights are from random-effects model.

Table 2. Multivariate regression analysis with interaction terms.

Outcome	Subgroup factor	Divided standard	Numbers of studies	HR (95% CI)	p-value	Heterogeneity		Effects model
						I^2 (%)	Phet
OS	Country	Italy	1	1.98 (1.47–2.67)	<0.001	–	–	FEM
		Turkey	2	1.74 (1.38–2.19)	<0.001	0.0	0.385	FEM
		USA	2	2.38 (1.66–3.42)	<0.001	0.0	0.750	FEM
		China	16	1.73 (1.49–2.02)	<0.001	62.3	<0.001	REM
	Sample size	≥200	13	1.70 (1.47–1.96)	<0.001	64.9	0.001	REM
		<200	8	2.02 (1.66–2.45)	<0.001	14.5	0.317	FEM
	SII cut-off value	≥900	5	2.22 (1.86–2.63)	<0.001	0.0	0.813	FEM
		<900	16	1.65 (1.44–1.88)	<0.001	52.4	0.008	REM
	Analysis type	MVA	20	1.81 (1.59–2.06)	<0.001	59.8	<0.001	REM
		UVA	1	1.42 (0.90–2.25)	0.135	–	–	FEM
PFS	Country	Italy	1	1.32 (1.05–1.67)	0.019	–	–	FEM
		Turkey	2	1.73 (1.40–2.13)	<0.001	4.2	0.307	FEM
		China	6	2.21 (1.55–3.16)	<0.001	62.1	0.022	REM
		USA	1	1.62 (1.07–2.46)	0.023	–	–	FEM
		Japan	1	0.38 (0.15–0.96)	0.041	–	–	FEM
	Sample size	≥200	3	1.69 (1.23–2.32)	0.001	72.9	0.025	REM
		<200	8	1.80 (1.27–2.53)	0.001	68.8	0.002	REM
	Analysis type	MVA	8	1.10 (0.71–1.72)	0.671	70.6	0.033	REM
		UVA	3	1.91 (1.64–2.21)	<0.001	44.9	0.08	FEM
	SII cut-off value	≥900	4	1.38 (0.84–2.26)	0.2	81.0	0.001	REM
		<900	7	1.92 (1.49–2.47)	<0.001	51.3	0.055	REM

FEM: Fixed-effects model; M: Multivariable; OS: Overall survival; PFS: Progression-free survival; REM: Random-effects model; U: Univariable.

Figure 3. Sensitivity analysis of (A) overall survival and (B) progression-free survival.

Figure 4. Publication bias assessment.

(A) Funnel plot for publication bias in overall survival; (B) Funnel plot adjusted by the trim and fill method in overall survival; (C) Funnel plot for publication bias in progression-free survival.

Berardi R, Santoni M, Rinaldi S et al. Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small-cell lung cancer. Ann. Transl. Med. 7(20), 572 (2019).

 PubMed Web of Science ®Google Scholar

Bilgetekin I, Basal FB. Systemic immune-inflammation index is the best prognostic factor in patients with advanced stage adenocarcinoma of the lung treated with pemetrexed. J. Coll. Physicians Surg. Pak. 30(9), 933–939 (2020).

 PubMed Web of Science ®Google Scholar

Coutu BG, Johnson KC, Bhirud A et al. Systemic immune-inflammatory index association with survival in patients undergoing trimodality therapy for lung cancer. Oncology 100(5), 247–256 (2022).

 PubMed Web of Science ®Google Scholar

Delikgoz SE, Kemal Y, Karacin C et al. Prognostic impact of immune inflammation biomarkers in predicting survival and radiosensitivity in patients with non-small-cell lung cancer treated with chemoradiotherapy. J. Med. Imaging Radiat. Oncol. 66(1), 146–157 (2022).

 PubMed Web of Science ®Google Scholar

Deng C, Zhang N, Wang Y et al. High systemic immune-inflammation index predicts poor prognosis in advanced lung adenocarcinoma patients treated with EGFR-TKIs. Medicine (Baltimore) 98(33), e16875 (2019).

 PubMed Web of Science ®Google Scholar

Fu F, Deng C, Wen Z et al. Systemic immune-inflammation index is a stage-dependent prognostic factor in patients with operable non-small-cell lung cancer. Transl. Lung Cancer Res. 10(7), 3144–3154 (2021).

 PubMed Web of Science ®Google Scholar

Gao Y, Zhang H, Li Y et al. Preoperative increased systemic immune-inflammation index predicts poor prognosis in patients with operable non-small-cell lung cancer. Clin. Chim. Acta 484, 272–277 (2018).

 PubMed Web of Science ®Google Scholar

Guo D, Zhang J, Jing W et al. Prognostic value of systemic immune-inflammation index in patients with advanced non-small-cell lung cancer. Future Oncol. 14(25), 2643–2650 (2018).

 PubMed Web of Science ®Google Scholar

Guo W, Cai S, Zhang F et al. Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients with surgically resected non-small-cell lung cancer. Thorac. Cancer 10(4), 761–768 (2019).

 PubMed Web of Science ®Google Scholar

Ju Q, Huang T, Zhang Y et al. Systemic immune-inflammation index predicts prognosis in patients with different EGFR-mutant lung adenocarcinoma. Medicine (Baltimore) 100(6), e24640 (2021).

 PubMed Web of Science ®Google Scholar

Keit E, Coutu B, Zhen W et al. Systemic inflammation is associated with inferior disease control and survival in stage III non-small-cell lung cancer. Ann. Transl. Med. 9(3), 227 (2021).

 PubMed Web of Science ®Google Scholar

Li A, Mu X, He K et al. Prognostic value of lymphocyte-to-monocyte ratio and systemic immune-inflammation index in non-small-cell lung cancer patients with brain metastases. Future Oncol. 16(30), 2433–2444 (2020).

 PubMed Web of Science ®Google Scholar

Li B, Wang S, Li C et al. The kinetic changes of systemic inflammatory factors during bevacizumab treatment and its prognostic role in advanced non-small-cell lung cancer patients. J. Cancer 10(21), 5082–5089 (2019).

 PubMed Web of Science ®Google Scholar

Li H, Wang G, Zhang H et al. Prognostic role of the systemic immune-inflammation index in brain metastases from lung adenocarcinoma with different EGFR mutations. Genes Immun. 20(6), 455–461 (2019).

 PubMed Web of Science ®Google Scholar

Li W, Qu Y, Wen F et al. Prognostic nutritional index and systemic immune-inflammation index are prognostic biomarkers for non-small-cell lung cancer brain metastases. Biomark Med. 15(13), 1071–1084 (2021).

 PubMed Web of Science ®Google Scholar

Li X, Hu P, Liu J et al. Systemic immune-inflammation index predicted overall survival and radiosensitivity in advanced non-small-cell lung cancer. Future Oncol. 16(5), 103–115 (2020).

 PubMed Web of Science ®Google Scholar

Liu J, Li S, Zhang S et al. Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab. J. Clin. Lab. Anal. 33(8), e22964 (2019).

 PubMed Web of Science ®Google Scholar

Shen YJ, Qian LQ, Ding ZP et al. Prognostic value of inflammatory biomarkers in patients with stage I lung adenocarcinoma treated with surgical dissection. Front Oncol. 11, 711206 (2021).

 PubMedGoogle Scholar

Takeda T, Yamada T, Tanimura K et al. Prognostic markers of survival among japanese patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer receiving first-line alectinib. Diagnostics (Basel) 11(12), 2170 (2021).

 PubMedGoogle Scholar

Tomita M, Ayabe T, Maeda R et al. Systemic immune-inflammation index predicts survival of patients after curative resection for non-small-cell lung cancer. In Vivo 32(3), 663–667 (2018).

 PubMed Web of Science ®Google Scholar

Tong YS, Tan J, Zhou XL et al. Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small-cell lung cancer. J. Transl. Med. 15(1), 221 (2017).

 PubMed Web of Science ®Google Scholar

Watanabe K, Noma D, Masuda H et al. Preoperative inflammation-based scores predict early recurrence after lung cancer resection. J. Thorac. Dis. 13(5), 2812–2823 (2021).

 PubMed Web of Science ®Google Scholar

Xu S, Cao S, Yu Y. High systemic immune-inflammation index is a predictor of poor prognosis in patients with nonsmall cell lung cancer and bone metastasis. J. Cancer Res. Ther. 17(7), 1636–1642 (2021).

 PubMed Web of Science ®Google Scholar

Yan X, Li G. Preoperative systemic immune-inflammation index predicts prognosis and guides clinical treatment in patients with non-small-cell lung cancer. Biosci. Rep. 40(3), BSR20200352 (2020).

 PubMedGoogle Scholar

Zhang Y, Chen Z, Jin F et al. The value of the systemic immune-inflammation index in predicting survival outcomes in patients with brain metastases of non-small-cell lung cancer treated with stereotactic radiotherapy. Mediators Inflamm. 2021, 2910892 (2021).

 PubMedGoogle Scholar