To date, there has been only one clinical research that focused on CCA IMT, assessed by B-mode ultrasonography and quantifying software, and allowed for direct demonstration of atherosclerotic changes in the vessel wall of post-radiotherapy NPC patients
. The current study confirms the posited hypothesis that radiation-induced vasculopathy is a dynamic and progressive process from late radiation effects and that the duration after radiotherapy correlates with the progression of carotid intima-media thickness.
In clinical practice, vascular abnormalities are the predominant histologic changes seen in irradiation for head and neck cancers seen more than 6 months after
. Among survivors of the cancer itself, late effects on "bystander" organs like the carotid arteries after irradiation have become increasingly prevalent, with secondary cardio-vascular disease increasing morbidity and mortality. Atherosclerotic and thrombotic complications have drawn the most attention
[14–17]. One study published in 2001 showed that the overall prevalence of extra-cranial carotid artery disease was 56 of 71 patients (78.9%). The common and internal carotid arteries were most commonly involved (77.5%), followed by the external carotid (45%) and vertebral (7%) arteries in the post-irradiation group. In contrast, the control group showed a 21.6% involvement of the common and internal carotid arteries, 2.0% external carotid arteries, and no involvement of the vertebral artery
Another study evaluated 910 patients who survived at least five years after irradiation of head and neck tumors had stroke in 6% and clinically significant carotid stenosis in 17%
. Furthermore, atherosclerotic plaques result from the interaction between modified lipids, extracellular matrix, monocyte-derived macrophages, and activated vascular smooth muscle cells that accumulate in the arterial wall. Plaque formation is often complicated by conversion into an acute stage of vessel occlusion or thrombo-embolism evolving from the plaque and resulting in acute clinical complications of myocardial infarction and stroke.
The present study, which examined the IMT of CCA in NPC patients post-radiotherapy and on follow-up for more than one year, has three major findings. First, the IMT of CCA is significantly increased in NPC patients compared to healthy control.significantly increased in NPC patients compared to healthy control. Second, 36.2% of NPC cases have carotid plaques and significant risk factors for carotid plaques include age, duration after radiotherapy, and HbA1c levels. The cut-off value of age and duration after radiotherapy for the presence of plaque are 52.5 years and 42.5 months, respectively. Third, age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count are positive correlated with IMT. Multiple linear regression analysis reveals that age, duration after radiotherapy and platelet counts are independently associated with CCA IMT. After adjustments for age, gender, and platelet counts, IMT increases in a linear manner with the duration after radiotherapy.
Although this study demonstrates that the duration after radiotherapy correlates with the progression of carotid intima-media thickness, there are two main limitations. First, the study does not exclude patients with underlying diseases of DM and hyperlipidemia and expressions of hs-CRP level and the platelet activation markers and IMT of CCA that may be influence by drugs (e.g. statins and calcium channel blockers), which may cause potential bias in the statistical analysis. Second, this is a cross-sectional study and therefore subject to bias of unmeasured factors. It is also not possible to assess the effect of radiotherapy on the change of IMT in the same individual.
In conclusion, radiation-induced vasculopathy is a dynamic and progressive process from the late radiation effects. This is important in the understanding of the pathogenesis of atherosclerosis in NPC patients after radiotherapy. Extra-cranial color-coded duplex sonography may be added in routine follow-up studies of NPC patients aged ≥50 years old at 40 months post-radiotherapy to reduce morbidity and mortality from atherosclerosis-related diseases. Large-scale trials evaluating the relationship between change of IMT and effects of radiotherapy in NPC patients are warranted to clarify optimal strategy.
The study was approved by Chang Gung Memorial Hospital’s Institutional Review Committee on Human Research.