Carotid artery stenosis in asymptomatic patients after ipsilateral head and neck radiotherapy

Abstract

1. To compare the incidence of stenosis in irradiated and unirradiated carotid arteries. 2. To quantify the degree of such stenoses/abnormalities and their clinical significance. 3. To examine other potential factors for stenosis in irradiated carotids. 40 subjects <80 years old were recruited. All had undergone ipsilateral neck irradiation for malignancy with curative intent at least 2 years previously. Median age was 63.5 years (range 27–79). Median interval from radiation to imaging was 86 months (range 24–217). 14 subjects had been treated for lymphoma, 12 received 30Gy in 10 fractions and 2 received 35Gy in 20 fractions. 18 subjects had been irradiated for tonsillar carcinoma, 14 had received 60Gy in 25 fractions and 4 received 50Gy in 20 fractions. 8 had been treated for parotid tumours, 2 received 60Gy in 25 fractions, 5 received 50Gy in 20 fractions and one received 50Gy in 25 fractions. The median dose equivalent in 2Gy fractions was 54.5Gy (range 33.4 to 64.3Gy). No subject had symptoms or clinical signs of carotid artery disease, all had fasting glucose and lipid blood testing, carotid ultrasonography and CT angiography. Recognized grading and classification systems were used to document carotid artery abnormalities. Matched pair analysis was performed using McNemar’s test for categorical variables. Putative factors for carotid stenosis were analysed using logistic regression, initially by univariate and then multivariate analysis. These included radiation dose; time from radiotherapy; age at radiotherapy; neck surgery; smoking, diabetes, hypercholesterolaemia and hypertension. The latter 4 were analysed as both categorical and continuous variables. 13 stenoses were found in irradiated carotids compared to 5 in the unirradiated side (p = 0.03) In irradiated carotids 9 stenoses were found in the bulb/internal carotid artery (ICA); 2 in the external carotid artery (ECA) and 2 in the common carotid artery (CCA). The ECA and CCA are not typical sites of isolated stenosis in unirradiated patients. Six irradiated carotids had a bulb/ICA stenosis ≥60%, only one unirradiated carotid had a similar lesion, Odds Ratio of 6:1 (p = 0.13 ). Using standard radiological criteria, irradiated carotid bulb walls had higher grade abnormalities than unirradiated ones. This was only statistically significant in subjects receiving an effective dose ≥50Gy in 20 fractions (p = 0.02). This implies a dose factor in the level of damage to the carotid bulb wall. CCA diameter was significantly reduced in the irradiated carotids: 7.70 vs 7.98mm; mean reduction 0.28mm, CI 0.5 to 0.05mm, p = 0.02. In both univariate and multivariate analysis, the only statistically significant risk factor, apart from radiotherapy, was smoking pack years (p = 0.02). Therapeutic doses of ionizing radiation result in increased carotid artery stenosis and vessel wall abnormalities. The use of a matched-pair study design of irradiated and unirradiated carotids in the same patient has avoided the selection bias inherent in previous studies, which compared irradiated patients with unirradiated controls. We demonstrated an increase in ICA wall disease with dose levels >35.5Gy. Six of forty irradiated carotids had an ICA/ Bulb stenosis ≥60%, which is often considered the threshold for further assessment and intervention. Only one such stenosis was found in an unirradiated vessel. Larger studies are planned to evaluate the absolute risk of stenosis caused by radiotherapy, meanwhile the risk of carotid stenosis should be borne in mind when planning treatment for head and neck tumours