Continuous and Early Progression of Carotid Intima-Media Thickness after Radiotherapy for Head and Neck Cancer: 5-Year Prospective Observational Study

Abstract

Introduction: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy.

Methods: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated.

Results: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01).

Discussion: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm.

Keywords: Atherosclerosis; Carotid artery stenosis; Head and neck cancer; Radiotherapy.

Fig. 1

Increase of mean IMT from initial examination (Δmean IMT) during 5-year observation after radiotherapy. The comparison between the RT group and the control group (a) and the comparison depending on radiation dose at CCAs (high dose; >40 Gy, low dose; ≤40 Gy, b). ** Indicates p < 001. IMT, intima-media thickness.

Fig. 2

Cumulative incidence curves for increase of mean IMT ≥0.25 mm from initial examination (Δmean IMT). a The comparison between the RT group and the control group. Sub-analysis of the RT group (b) and the control group (b) according to initial mean IMT. d The comparison of the RT group between the high dose group and the low group (high dose; >40 Gy, low dose; ≤40 Gy). IMT, intima-media thickness.