Impact of radiotherapy for nasopharyngeal carcinoma on carotid stenosis risk: a meta-analysis

Liang, Huiqing; Zhou, Yuanyong; Xiong, Wei; Zheng, Suimin

doi:10.1016/j.bjorl.2022.03.001

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Brazilian Journal of Otorhinolaryngology

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Sumário

ORIGINAL ARTICLE • Braz. j. otorhinolaryngol. 88 (Suppl 4) • 2022 • https://doi.org/10.1016/j.bjorl.2022.03.001 copy

Impact of radiotherapy for nasopharyngeal carcinoma on carotid stenosis risk: a meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objects:

Radiotherapy (RT) serves as the most effective treatment for Nasopharyngeal Carcinoma (NPC) and can cause carotid stenosis. The aim of this study is to assess the impact of RT on carotid stenosis in NPC patients, as well as to explore the risk factors for significant carotid stenosis.

Methods:

Studies reporting the carotid stenosis in NPC patients who underwent RT were found on PubMed, Embase and Web of Science. Outcomes of our interest included incidence of overall/significant stenosis, Common Carotid Artery (CCA) stenosis, External Carotid Artery (ECA) stenosis, Internal Carotid Artery (ICA) stenosis, and risk factors for significant carotid stenosis.

Results:

Sixteen studies met the inclusion criteria and were included in this meta-analysis. Pooled estimate showed that RT was associated with a significantly higher incidence of overall stenosis (Risk Ratio [RR = 3.53], 95% CI: 2.32–5.37; p < 0.001) and significant stenosis (RR = 7.06, 95% CI: 3.61–13.79; p < 0.001) as compared with controls. Moreover, patients treated with RT had a significantly higher risk of stenosis in CCA (RR = 6.87, 95% CI: 4.08–11.58; p < 0.001), ICA (RR = 3.43, 95% CI: 1.35–8.73; p= 0.010), ECA (RR = 9.37, 95% CI: 2.06–42.68; p = 0.004), and ECA/ICA (RR = 2.18, 95% CI: 1.52–3.13; p < 0.001). Meta-analysis indicated that age (RR = 1.46, 95% CI: 1.05–2.04; p = 0.024), smoking habit (RR = 1.20, 95% CI: 1.02–2.78; p = 0.045) and time interval from radiotherapy (RR = 1.56, 95% CI: 1.07–2.28; p = 0.02) were independent predictors of significant carotid stenosis.

Conclusion:

Our results suggested that RT increased the risk of carotid stenosis in patients with NPC. Prevention and control measurements should be made for older NPC patients with longer interval from RT, especially those with smoking habit.

Level of evidence:

KEYWORDS
Nasopharyngeal carcinoma; Radiotherapy; Carotid stenosis; Meta-analysis

HIGHLIGHTS

Radiotherapy (RT) serves as the most effective treatment for Nasopharyngeal Carcinoma (NPC) and can cause carotid stenosis.

This meta-analysis of 16 studies assessed the impact of RT on carotid stenosis in NPC patients, as well as to explore the risk factors for significant carotid stenosis.

Results showed that RT increased the risk of carotid stenosis in patients with NPC. Age, smoking habit and time interval from radiotherapy were independent predictors of significant carotid stenosis.

Study	Country	Year of publication	Study design	Radiotherapy dose (Gy)	Subjects	Nº of patients	Interval from RT (years)	Male/ Female	Age (mean ± SD, y)	NOS score
Zhou L¹⁴14 Zhou L, Xing P, Chen Y Xu X, Shen J, Lu X. Carotid and vertebral artery stenosis evaluated by contrast-enhanced MR angiography in nasopharyngeal carcinoma patients after radiotherapy: a prospective cohort study. Br J Radiol. 2015;88:20150175.	China	2015	Cohort	66.0	NPC NPCWR	72 50	5.7 (3–16)	44/28 29/21	54 (19–81) 54 (20–85)	7
Chang YJ ¹⁵15 ChangYJ, Chang TC, LeeTH, RyuSJ. Predictors of carotid artery stenosis after radiotherapy for head and neck cancers. J Vasc Surg. 2009;50:280–5.	China	2019	Cross-sectional study	6000cGy	NPC NPCWR	192 98	2.0 (0.3–19.1)	139/53 71/27	49.9 ± 11.7 49.8 ± 12.5	6
Cheng WS¹⁶16 Cheng SW, Wu LL, Ting AC, Lau H, Lam LK, Wei WI. Irradiation-induced extracranial carotid stenosis in patients with head and neck malignancies. Am J Surg. 1999;178:323–8.	China	1999	Cross-sectional study	5500cGy	NPC NPCWR	85 108	6.4 ± 5.5	NR NR	59.3 ± 14.0 62.1 ± 10.3	5
Cheng WS¹⁷17 Cheng SW, Ting AC, Lam LK, WeiWI. Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2000;126:517–21.	China	2000	Cross-sectional study	60–66	NPC NPCWR	96 96	6.7	NR NR	53.6 61.8 ± 10.5	5
Dubec JJ¹⁸18 Dubec JJ, Munk PL, Tsang V, Lee MJ, Janzen DL, Buckley J, et al. Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy. Br J Radiol. 1998;71:872–5.	Canada	1998	Cross-sectional study	5950cGy	NPC HS	45 45	NR	30/15 NR	67 NR	6
Huang TL¹⁹19 Huang TL, Hsu HC, Chen HC, Lin HC, Chien CY, Fang FM, et al. Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma. Rad Oncol. 2013;8:261.	China	2013	Cross-sectional study	68.4–78.6	NPC HS	105 25	4.0	72/33 16/9	52.43 ± 10.23 50.68 ± 11.49	5
Lam WW²⁰20 Lam WW, Leung SF, So NM, Wong KS, Liu KH, Ku PK, et al. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer. 2001;92:2357–63.	China	2001	Cross-sectional study	56.4	NPC NPCWR	71 51	4–20	53/18 35/16	53.6 (38–64) 48.8 (26–87)	6
Lam WW²¹21 Lam WW, Liu KH, Leung SF, Wong KS, So NM, Yuen HY, etal. Sonographic characterisation of radiation-induced carotid artery stenosis. Cerebrovasc Dis. 2002;13:168–73.	China	2002	Case-control study	56.6	NPC NPCWR	71 142	4–11	52/19 91/51	53.6 (39–69) 60.6 (20–83)	7
Greco A²²22 Greco A, Gallo A, De Virgilio A, Marinelli C, Macri GF, Fusconi M, et al. Carotid stenosis after adjuvant cervical radiotherapy in patients with head and neck cancers: a prospective controlled study. Clin Otolaryngol. 2012;37:376–81.	Italy	2012	Cohort study	50–60	NPC NPCWR	39 54	NR	31/8 40/14	62.1 63.7	5
Li CS²³23 Li CS, Schminke U, Tan TY. Extracranial carotid artery disease in nasopharyngeal carcinoma patients with post-irradiation ischemic stroke. Clin Neurol Neurosurg. 2010;112:682–6.	China	2010	Case-control study	4500–8100 cGy	NPC HS	43 276	5	31/12 166/110	56 ± 7 64 ± 12	5
Liao W²⁴24 Liao W, Zhou H, Fan S, Zheng Y Zhang B, Zhao Z, et al. Comparison of significant carotid stenosis for nasopharyngeal carcinoma between intensity-modulated radiotherapy and conventional two-dimensional radiotherapy. Scient Rep. 2018;8:13899.	China	2018	Case-control study	66.5 ± 4.7	NPC NPCWR	96 137	6.3	73/23 113/24	51 (29–75) 52 (24–72)	6
Ye JH²⁵25 Ye J, Rong X, Xiang Y Xing Y Tang Y A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis. PloS One. 2012;7:e42890.	China	2012	Case-control study	60–64	NPC HS	91 29	4.53 ± 1.69	66/25 21/8	38.29 ± 4.66 38.10 ± 5.35	7
Chu PY²⁶26 Chu PY, Tsang J, Wong WY, Chan W, Poon WL, Yuen MK, et al. Radiotherapy for nasopharyngeal carcinoma as a risk factor for extracranial carotid stenosis. is it also a risk factor for intracranial arteries? A retrospective case-control study. Hong Kong J Radiol. 2015;18:180–6.	China	2015	Case-control study	NR	NPC NPCWR	19 133	14.8 (2–30)	NR NR	64.9 ± 11.6 64.9 ± 11.6	5
Tai SML²⁷27 Tai SML, Niyaz M, Ng CG, Govindasamy G, Tan CT. Extracranial carotid stenosis after radiotherapy in nasopharyngeal carcinoma, a Malaysian study. Neurol Asia. 2013;18:143–51.	Malaysia	2013	Case-control study	66	NPC HS	47 47	6.4 ± 7.9	31/16 31/16	55.1 ± 12.4 55.0 ± 12.9	6
Yuan C²⁸28 Yuan C, Wu VW, Yip SP, Kwong DL, YingM. Ultrasound evaluation of carotid atherosclerosis in post-radiotherapy nasopharyngeal carcinoma patients, type 2 diabetics, and healthy controls. Ultraschall Medizin. 2017;38:190–7.	China	2017	Case control study	66.87 ± 3.45	NPC HS	69 76	≥4	28/41 37/39	52.6 ±8.4 42.8 ± 15.5	7
Lam WW²⁹29 Lam WW, Yuen HY, Wong KS, Leung SF, Liu KH, Metreweli C. Clinically underdetected asymptomatic and symptomatic carotid stenosis as a late complication of radiotherapy in Chinese nasopharyngeal carcinoma patients. Head Neck. 2001;23:780–4.	China	2001	Case control study	56.6	NPC NPCWR	80 58	4–26	NR NR	53 (38–69) 53 (38–69)	6

Variable	RR	95% CI	p
Age	1.46	1.05–2.04	0.024
Smoking habit	1.20	1.02–2.78	0.045
Time interval from RT	1.56	1.07–2.28	0.020
Gender	1.32	0.72–2.41	0.365
RT dose	0.02	0.01–13.61	0.249
Hypertension	1.80	0.61–5.29	0.289
Diabetes mellitus	1.50	0.68–3.31	0.317
Heart disease	6.45	0.25–166.28	0.261
Hyperlipdemia	1.77	0.70–4.43	0.226
Surgery	0.27	0.03–2.20	0.222

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
E-mail: revista@aborlccf.org.br

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[1] *Corresponding author. E-mail:Lianghq396@126.com (H. Liang).