FDG-PET/CT and NaF-PET/CT in the diagnosis and assessment of radiation therapy-induced vascular complications in patients with head and neck cancer

Introduction: Globally, more than 800,000 people are diagnosed with head and neck cancer each year. These malignancies are treated with varying combinations of surgery, radiation, and chemotherapy but many of these patients will receive photon beam radiation therapy (RT) as definitive or adjunct treatment. Despite recent advances, RT interventions are associated with significant toxicity and higher rates of cardiovascular disease, which can present acutely or months to years afterward, often in the form of vasculitis or accelerated atherosclerosis of the irradiated arteries. A 2016 study examining over 14,000 patients with head and neck squamous cell carcinomas found that patients who received RT had a 70% increased risk of ischemic stroke when compared with patients who received surgery alone. RT toxicity is an increasingly recognized cause of morbidity and mortality yet clear guidelines for screening, assessment, and prevention have yet to be established. In this review, we examine the published literature related to the use of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and [18F] sodium-fluoride (NaF-PET) imaging to assess RT-induced vascular complications in patients with head and neck cancer.

Methods: Multiple databases including but not limited to Google Scholar and PubMed were accessed to compile a comprehensive body of literature related to FDG-PET and NaF-PET imaging of RT-induced vascular complications in patients with head and neck cancer. Journal articles examining the use of FDG-PET and NaF-PET in the assessment of RT-induced vasculopathy in other malignancies were referenced as well.

Results: FDG-PET computed tomography (FDG-PET/CT) has demonstrated clinical utility in the diagnosis and assessment of RT-induced inflammation. Prior studies examining RT-induced heart disease with FDG-PET/CT have demonstrated significant increases in the average standardized uptake value (SUV) mean between pre-RT and post-RT PET scans and noted higher global cardiac SUV means following RT of left-sided lesions. A study that assessed RT-induced vasculopathy in 45 non-small cell lung cancer patients found a significant increase in avg SUVmean of the ascending aorta (AA) and arch of the aorta (AoA) across all patients between pre-RT and post-RT PET scans (p<0.001). Another study that assessed global FDG uptake in the left common carotid (LCC) and AoA of 30 head and neck cancer patients before and after 3 months of photon RT demonstrated significantly increased avg SUVmean in the LCC (p=0.0004) and the AoA (p=0.004).

The elevated risk of ischemic stroke in head and neck cancer patients treated with photon RT is thought to be related, at least in part, to the generation of reactive oxygen species (ROS) that damage DNA and blood vessels accelerate atherosclerotic plaque formation. In this domain, researchers have applied NaF-PET/CT to assess micro-calcification in early atherosclerotic plaques and track their progression through time with high sensitivity. One study with 128 subjects noted that the SUVmax of NaF uptake in the LCC was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA p<0.01) and thromboembolic events (one-way ANOVA p<0.01), while it was significantly lower in patients with a greater level of physical activity (one-way ANOVA p<0.02).

Conclusions: FDG-PET/CT is ideally suited for assessing RT-induced inflammation. Further study is warranted to examine the role of NaF-PET in the diagnosis and assessment of vascular micro-calcification. A combined approach with FDG and NaF-PET might provide further information on the pathologic nature of vascular complications following RT and help differentiate vasculitis from vasculitis with superimposed atherosclerosis. Knowledge gained from the application of these techniques in larger cohorts could inform future RT treatment planning for patients with head and neck cancer and reduce future RT-induced cardiovascular complications.