Clinicopathological and prognostic significance of circulating tumor cells in patients with head and neck cancer: a meta-analysis

Figures & data

Figure 1 Selection of the included studies.

Table 1 Basic characteristics of the retrieved studies

Study	Year	Number CTC+/total	Area	Tumor stage	Sample site/time	Markers	Methods	Follow-up duration (months)
Li et al^Citation10	2016	20/38	China	I–IV	PB/before/1w/1m TM	CD45 DAPI	Immunomagnetic	–
Hsieh et al^Citation11	2015	17/53	Taiwan	II–IV	PB/before TM	EpCAM/PDPN	PowerMag immunofluorescence	10.5
Inhestern et al^Citation12	2015	32/40	Germany	III–IV	PB/before/during/after TM	EpCAM	Laser scanning cytometry	24.7
Grisanti et al^Citation18	2014	14/53	Italy	III–IV	PB/before/during TM	EpCAM/CD45/DAPI	CellSearch	25.0
Weller et al^Citation19	2014	7/10	Germany	I–IV	PB/before TM	CK/CD45/DAPI	Immunofluorescence	18
Tinhofer et al^Citation20	2014	42/144	Germany	I–IV	PB/before TM	EGFR mRNA	RT-PCR	34
Grobe et al^Citation21	2014	10/80	Germany	I–IV	PB/before TM	EpCAM/CD45/DAPI	CellSearch	30.1
Bozec et al^Citation22	2013	8/49	France	III–IV	PB/before TM	EpCAM/CD45/DAPI	CellSearch	6
He et al^Citation23	2013	3/9	China	III–IV	PB/before TM	EpCAM/CD45/DAPI	CellSearch	16
Buglione et al^Citation24	2012	11/73	Italy	I–IV	PB/before TM	EpCAM/CD 45/DAPI	CellSearch	13.6
Nichols et al^Citation25	2012	6/15	Britain	III–IV	PB/before TM	EpCAM/CD 45/DAPI	CellSearch	8
Hristozova et al^Citation26	2011	18/42	Germany	I–IV	PB/before TM	EpCAM, CK	Flow cytometry	–
Jatana et al^Citation27	2010	34/48	USA	I–IV	PB/during TM	CK, CD45, DAPI	Immunocytochemistry	38
Toyoshima et al^Citation28	2009	14/40	Germany	I–IV	PB/after TM	CK20	RT-PCR	43.5
Guney et al^Citation29	2007	7/21	Turkey	I–IV	PB/before TM	EpCAM	MACS	36
Wollenberg et al^Citation30	2004	54/176	Germany	I–IV	BM/before TM	CK19	IHC-APAAP	60
Wirtschafter et al^Citation31	2002	8/18	USA	I–IV	PB/before TM	CK20	Immunocytochemistry	–

Abbreviations: CTC, circulating tumor cell; w, weeks; m, months; mRNA, messenger RNA; RT-PCR, reverse transcription–polymerase chain reaction; PB, peripheral blood; BM, bone marrow; IHC, immunohistochemistry; TM, treatment; DAPI, 4′,6-diamidino-2-phenylindole; EpCAM, epithelial cell adhesion molecule; PDPN, podoplanin protein; CK, cytokeratin; EGFR, epidermal growth factor receptor; MACS, magnetic cell separation; APAAP, alkaline phosphatase-anti-alkaline phosphatase technique.

Table 2 The assessment of the risk of bias in each cohort study using the NOS

Study	Selection				Comparability		Outcome			Star
	Exposed cohort	Non-exposed cohort	Ascertainment of exposure	Demonstration outcome	Basic factors	Additional factors	Assessment	Follow-up	Adequacy
Li et al^Citation10	0	1	1	1	1	0	0	0	0	4
Hsieh et al^Citation11	1	1	1	1	0	0	1	1	0	6
Inhestern et al^Citation12	0	1	1	1	0	0	1	1	1	6
Grisanti et al^Citation18	0	1	1	0	1	0	1	1	1	6
Weller et al^Citation19	1	1	1	0	0	0	1	1	0	5
Tinhofer et al^Citation20	1	1	1	0	1	0	1	1	0	6
Grobe et al^Citation21	1	1	1	1	0	0	1	1	1	7
Bozec et al^Citation22	0	1	1	1	1	0	0	0	0	4
He et al^Citation23	0	1	1	1	0	0	1	0	0	4
Buglione et al^Citation24	1	1	1	1	1	0	1	0	0	6
Nichols et al^Citation25	0	1	1	1	0	0	1	0	0	4
Hristozova et al^Citation26	1	1	1	1	1	0	0	0	0	5
Jatana et al^Citation27	1	1	1	0	0	0	1	1	1	6
Toyoshima et al^Citation28	1	1	1	0	1	0	1	1	1	7
Guney et al^Citation29	0	1	1	1	1	0	1	0	0	5
Wollenberg et al^Citation30	1	1	1	1	1	0	1	0	0	6
Wirtschafter et al^Citation31	1	1	1	0	1	0	0	0	0	4

Abbreviation: NOS, Newcastle–Ottawa scale.

Figure 2 Meta-analysis of clinicopathological characteristics, (A) tumor infiltration, (B) node metastasis, (C) TNM stage, (D) pathological grade, (E) age and (F) sex.

Abbreviations: TNM, tumor–node–metastasis; RR, risk ratio; CI, confidence interval.

Note: Weights are from random effective analysis.

Figure 3 Meta-analysis of prognostic value, (A) OS, (B) DFS, (C) PFS and (D) recurrence.

Note: Weights are from random effective analysis.
Abbreviations: OS, overall survival; DFS, disease-free survival; PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; RR, risk ratio.

Figure 4 Sensitivity analysis for the pooled prognostic value, (A) OS, (B) DFS, and (C) recurrence.

Abbreviations: OS, overall survival; DFS, disease-free survival; CI, confidence interval.

Table 3 Publication bias by Egger’s and Begg’s test

Variables	P-value
	Egger’s	Begg’s
Age	0.849	>0.999
Sex	0.514	0.711
Tumor infiltration	0.45	0.348
Node metastasis	0.252	0.213
TNM stage	0.825	0.536
Pathological grade	0.309	0.462
Recurrence	0.328	0.174
PFS	–	>0.999
DFS	0.862	0.734
OS	0.053	0.089

Abbreviations: TNM, tumor–node–metastasis; PFS, progression-free survival; DFS, disease-free survival; OS, overall survival.

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