The field of cardio-oncology continues to expand rapidly. A recent manuscript by Shah et al (1) assessed the effects of radiation therapy (RT) on the carotid arteries of individuals receiving RT for treatment of head and neck cancer. The ultimate aim of the study was to establish whether plaque formation or intraplaque complications develop as a result of RT, which could explain the increased risk of stroke reported by previous studies assessing cancer patients undergoing neck RT.(2) The Shah study (1) was a cross-sectional investigation in 49 patients who had undergone unilateral RT for head and neck cancer ≥2 years previously. The carotid arteries of these patients were assessed with B-mode and contrast-enhanced ultrasound.  Both the RT and non–RT carotid arteries were investigated in each case. Interestingly, the number of plaques found by the investigators was significantly greater in the RT than the non-RT carotid arteries and, among patients with plaques, intraplaque neovascularisation was present in 81% of patients with RT-side plaques compared with 41% of patients with non-RT-side plaques (p = 0.004). This study thus showed a significant association between RT and the presence and extent of intraplaque neovascularisation.

An editorial article by Arbustini et al. (3) expands on the Shah et al. findings (1) indicating that several studies have previously demonstrated that RT in patients with head and neck cancer “is associated with: a) increased intimal medial thickness of the carotid wall; b) narrowing of the lumen; c) occurrence of new atherosclerotic plaques; and d) worsening of pre-existing plaques”. Moreover, they cited work showing that carotid disease resulting from RT is associated with an increased risk of stroke and cardiovascular events. (2) Of interest, these findings are not limited to only the adult population as also paediatric patients may be affected. Indeed, children who have survived cancer after treatment with RT were found to have significant signs of premature arterial aging during young adulthood (4). The consistency of findings in different study populations makes it mandatory –as suggested by Arbustini et al (3)- that the carotid arteries are protected during RT and this should be followed by the implementation of appropriate monitoring strategies to detect vascular changes that can potentially lead to serious events.  Current RT techniques and protocols do contemplate these needs (5) and future studies will hopefully show a reduced incidence of carotid RT related disease.

More research is required, however, to understand the different types of carotid disease resulting from RT, as studies seem to differ as to the “pathobiological” characteristics of plaques found in different patients. Another area of research that needs further development –as suggested by Arbustini et al (3)- is whether plaques associated with increased risk of stroke can be identified as early as possible in the clinical setting to try and develop more effective preventative strategies. Dynamic imaging techniques are available that may serve the purpose. Close research collaboration among vascular biologists, pathologists and imaging experts may help speeding up the process.

References

1. Shah BN et al. Plaque neovascularization is increased in human carotid atherosclerosis related to prior neck radiotherapy. A contrast enhanced ultrasound study. J Am Coll Cardiol Img. 2016; doi:10.1016/j.jcmg.2015.07.026
2. Swisher-McClure S et al. Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer. Head Neck 2014; 36: 611–616
3. Arbustini E et al. Radiation Therapy for Head and Neck Cancer and Angioneogenesis: Good for Cancer, Bad for Carotids? – JACC Cardiovascular Imaging 2016 –
4. Vatanen A et al. Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood. Pediatr Blood Cancer 2015; 62: 2000–2006
5. Rosenthal DJ et al. Simple carotid-sparing intensity-modulated radiotherapy technique and preliminary experience for T1-2 glottic cancer. Int J Radiat Oncol Biol Phys 2010; 77: 455–461