Carotid ultrasound to identify head and neck cancer survivors with high cardiovascular risk after radiation therapy: rationale and design of a prospective, cross-sectional pilot study.

Background: Radiation therapy is an integral component of treatment that can predispose to carotid artery stenosis (CAS) and increase the risk of cerebrovascular events for head and neck cancer survivors. The utility of screening for CAS with carotid ultrasound in asymptomatic head and neck cancer survivors is unclear.Methods: In this prospective, cross-sectional pilot study, 60 patients who have no evidence of cancer at least 2 years from completion of RT will undergo screening carotid ultrasound to identify patients with high risk of cardiovascular events.Results: Outcomes will include clinically significant CAS, carotid intima-media thickness, acceptability/feasibility of screening, barriers to care and preliminary data on changes to medical management because of screening. Correlative multi-omics analyses will examine biomarkers of CAS after radiation therapy.Conclusion: The results of this study will provide valuable data on the prevalence of CAS and preliminary patient-centered data that will inform the design of a future large-scale, multi-site clinical trial.Clinical Trial Registration: NCT05490875 (ClinicalTrials.gov).

Patients with head and neck cancer are often treated with radiation therapy. Radiation therapy can cause damage to the blood vessels in the neck. This damage can manifest as narrowing of the blood vessels like the carotid artery, which can lead to stroke. Currently, it is not clear if screening head and neck cancer survivors with ultrasound scans of the carotid arteries is feasible or acceptable to patients. This has also not been formally assessed using a prospective clinical trial. In this study, patients with a history of head and neck cancer who have no evidence of their cancer for at least 2 years since completion of their radiation therapy will be enrolled. They will undergo blood testing and a research ultrasound of the carotid arteries to check for narrowing and other findings that may signal a high risk of stroke or another cardiovascular event. Participants will complete surveys on their experience with the process and how likely they are to accept further screening or additional treatment if something is found. They will also complete surveys on their perception of their personal risk of stroke and barriers to care that would prevent them from getting screening ultrasounds. Patients will be followed for up to 6 months after the ultrasound to check for any changes in their medical care that occurred because of the screening ultrasound.

Effects of Neck Radiation on Result of Doppler Sonography of Carotid Arteries in Head and Neck Cancer Patients.

PURPOSE: The aim of this study was to assess the effects of neck radiation on the results of Doppler sonography of carotid arteries in head and neck cancer patients. METHODS: In this prospective, cross-sectional study, 25 consecutive patients with head and neck cancers were assessed for carotid artery stenosis (CAS) by carotid color Doppler sonography before external radiotherapy and six months after external radiotherapy. Main outcome measures were peak systolic velocity (PSVs), end-diastolic velocities (EDVs) of the internal carotid artery (ICA), ICA/common carotid (CCA) ratios, and degree of stenosis. RESULTS: The age of the enrolled patients at the initiation of radiotherapy was 57.9±11.8 years (mean±SD; range, 43-91 years), and only 4 (16%) of the 25 patients were female. The findings showed significant changes in the plaque degree and stenosis degree, and plaque size before and after external radiotherapy (P<0.05). Changes in degree of stenosis were significantly correlated with age (p=0.021). CONCLUSION: After neck irradiation changes in the carotid artery may occur and cause subsequent neurologic events.

The effectiveness of high-resolution ultrasound in the assessment of the carotid intima-media thickness for postirradiated neck.

OBJECTIVE: The carotid intimal-medial thickness (CIMT) is a strong predictor of future cardiovascular events. We assessed the mean CIMT and evaluated associated factors in head and neck cancer (HNC) patients. MATERIALS AND METHODS: Between January 2016 and March 2018, 70 volunteers underwent automatic ultrasound measurement of the common carotid artery CIMT. A mean CIMT ≥ 1.0 mm was regarded as an elevated risk for cardiovascular disease (CVD). We aimed to investigate the risk factors for an increased mean CIMT. RESULTS: We recruited 20 HNC survivors and 50 noncancer control individuals. Multiple linear regression analysis showed that old age (ß = 0.006, 95% confidence interval, CI 0.004-0.008), increased weight (ß = 0.003, 95% CI 0.001-0.005), hypertension (ß = 0.10, 95% CI 0.03-0.17), and prior irradiation (ß = 0.13, 95% CI 0.08-0.19) were positively correlated with the mean CIMT. From logistic regression analysis, it was shown that patients who underwent radiotherapy (OR 13.5, 95% CI 1.48-122.8) and who had higher bodyweight (OR 1.09, 95% CI 1.01-1.18) had a significantly higher risk of developing CVD. CONCLUSION: Measurement of the mean CIMT using ultrasound could be useful for assessing CVD risk in HNC survivors after neck irradiation.

Radiation-induced carotid artery lesions.

PURPOSE: To review the current aspects of knowledge related to the risk of cerebrovascular events in patients receiving head and neck radiotherapy. METHODS: A literature search was performed in PubMed. Papers meeting selection criteria were reviewed. RESULTS: We provide an update on the problem by identifying key studies that have contributed to our current understanding of the epidemiology, radiologic features, pathogenesis, and treatment of the disease. The incidence of carotid artery stenosis ranged from 18 to 38% in patients who underwent radiotherapy for head and neck cancer versus from 0 to 9.2% among the nonirradiated patients. Neck irradiation increases the intima-media thickness of the carotid artery wall. These changes are the earliest visible alteration in the carotid wall and are also detected with color Doppler ultrasonography. Endovascular treatment with a carotid angioplasty and stenting is the first-line treatment for most symptomatic patients. CONCLUSIONS: Radiation-induced atherosclerosis is a different and accelerated form of atherosclerosis, which implies a more aggressive disease with a different biologic behavior. The disease is characterized by a high rate of carotid artery stenosis compared to those observed in nonirradiated control group patients. To prevent the risk of stroke, surveillance and imaging with ultrasonography should enable detection of severe stenosis. Endovascular treatment with a carotid angioplasty and stenting has been proposed as an attractive and minimally invasive alternative for some radiation-induced stenoses.

Magnetic resonance imaging of the carotid artery in long-term head and neck cancer survivors treated with radiotherapy.

BACKGROUND: In head and neck cancer (HNC) patients, long-term treatment-related complications include radiotherapy (RT)-induced carotid vasculopathy and stroke. The current study investigated the magnetic resonance imaging (MRI) characteristics of the carotid wall in long-term HNC survivors treated with RT. METHODS: MRI of the carotid arteries was performed within a prospective cohort of 42 HNC patients on average 7 years after RT. Two independent radiologists assessed maximal vessel wall thickness of common and internal carotid arteries. In case of wall thickening (≥ 2 mm) the MRI signals as well as length of the thickened segment were assessed. RESULTS: Mean (SD) age of the 42 patients at baseline was 53 (13) years and mean (SD) follow-up time after RT was 6.8 (1.3) years. In total 62% were men and 60% had one or more cerebrovascular risk factors. Mean (SD) dose of RT on the common carotid arteries and internal carotid arteries was 57 Gy (11) and 61 Gy (10), respectively. Wall thickening was observed in 58% of irradiated versus 27% of non-irradiated common carotid arteries and 24% of irradiated versus 6% of non-irradiated internal carotid arteries (p < 0.05). Mean (SD) thickness of the irradiated and non-irradiated common carotid arteries was 2.5 (0.9) and 2 (0.7) mm (p = 0.02). Mean thickness of the irradiated and non-irradiated internal carotid arteries was 1.8 (0.8) and 1.5 mm (0.3) (n.s.). Mean length of the thickened vessel wall was 48 mm versus 36 mm in the irradiated versus non-irradiated common carotid arteries (p = 0.03) and 20 mm versus 15 mm in the irradiated versus non-irradiated internal carotid arteries (n.s.). No significant differences were observed for signal intensities of the vessel walls. CONCLUSIONS: Our study showed significantly more vessel wall thickening in irradiated versus non-irradiated carotid arteries years after RT for HNC, while no differences in signal intensities were observed.

Carotid artery stenting using a transapical approach for the treatment of radiation-induced carotid stenosis.

Radiation-induced stenosis of the carotid artery is considered a challenging entity for direct revascularization. We performed a carotid artery stenting for a radiation-induced stenosis using a transapical approach on an asymptomatic 63-year-old male patient. Transapical approach, which is often used for cardiac surgery, was not yet described for the endovascular treatment of carotid stenosis. The transapical approach could be an attractive alternative path for patients presenting significant supra-aortic trunks lesions and unfit for direct approach or peripheral access. This case reports the feasibility and the safety of carotid artery stenting using the transapical approach in well-trained teams.

Prospective cohort study of carotid intima-media thickness after irradiation.

BACKGROUND: Carotid artery vasculopathy is a potential long-term complication after radiotherapy (RT) of the neck, resulting in cerebrovascular events. The underlying pathophysiology is not well understood and early markers are lacking. We aimed to study whether RT of the neck is associated with increase in carotid intima-media thickness (IMT) and stroke in the first 2 years after RT in patients with head and neck cancer (HNC). METHODS: In this prospective cohort study patients treated with RT of the neck were assessed for measurement of IMT before and 2 years after RT. Endpoints were changed in IMT and incidence of first-ever stroke. RESULTS: Between 2003 and 2008 we included 69 patients (median age, 57 years [25%-75% quartile, 51-64 years], median dose of RT 66 Gy [interquartile range, 60-70]) with baseline and follow-up measurement of IMT. Median IMT at baseline and follow-up was .60 and .62 mm (ratio of geometric means 1.01; 95% confidence interval, .96-1.08; P = .63). Four of 69 patients suffered from a stroke. Mean interval from RT to stroke was 6.8 months. CONCLUSIONS: Our study showed no increase of carotid IMT in the first 2 years after RT of the neck in patients treated for HNC. This indicates that the IMT is not a reliable early marker for postirradiation vasculopathy. However, a high rate of strokes was observed. A longer follow-up period is needed to find the starting point of RT-induced vascular changes.

[The influence of radiotherapy of head and neck cancers on carotid arteries]. / Wplyw radioterapii nowotworów glowy i szyi na tetnice szyjne.

INTRODUCTION: Modern radiotherapy of head and neck cancers involves high dosage of radiation per tissue volume including carotid arteries. Little is known about the mechanism of influence of radiotherapy to the large carotid arteries it may lead to inflammatory condition in the vascular wall, intima-media thickness (IMT) of the vessel and increase atherosclerosis. This work is based on current knowledge and presents the results of research which is based on ultrasound assessment of IMT and atheromatous changes in the carotid artery in a group of 61 irradiated patients with head and neck tumors. OBJECTIVES: To assess IMT, the progression of the atheromatous changes in the carotid arteries of patients who had completed radiotherapy in comparison with a control group of non-treated patients and to determine the relation between the progression of the atheromatous changes, the radiation dosage and time after their radiotherapy. PATIENTS AND METHOD: The ultrasound tested carotid arteries of 61 patients. The mean of the dose in the carotid area was 50.7 ± 10.6 Gy, and the time after the therapy completion was 41 ± 27 months. The results were compared with the measurement in the control group--62 people of similar age and risk of atherosclerosis. The stenosis was assessed using planimetric and hemodynamic methods and the structure of the plaque was assessed according to Gray-Weale. RESULTS: The average size of IMT on the front wall of the common carotid artery (CCA) is significantly bigger than on the opposite wall, p = 0.0149. There was shown no statistic difference concerning the average size of IMT (assessed on the posterior wall of the arteries) between the group of patients after radiotherapy and the control group (p = 0.1877). It has been proven that the frequency of occurrence of plaque in the carotid arteries in the patients who had completed radiotherapy compared to the control group is 16.3% bigger. The dominant type of plaque in the group of patients who had completed radiotherapy are heterogeneous plaques with majority of low echoes Type 2 or high echoes Type 3. The surface of the plaque in the group of patients is mostly irregular in comparison with the control group. There is no relationship between the thickness of IMT and the size of dosage. However, when considering the age of the patients there is an increase of IMT depending on the radiation dosage. It has been proven that the increase of IMT for patients below 63 years of age is bigger than for patients over 63. In the last statistical analysis, which studied the influence of time after the termination of treatment on the IMT, it has been proven that there is a small correlation of there parameters but not significant from the statistical point of view. CONCLUSION: The results of the research show that radiotherapy influences large carotid arteries by accelerating the IMT in the younger age group below 63 years of age. Radiation increases the frequency of plaque in carotid ateries and the creation of plaque of heterogeneous structure. Understanding the increase of IMT and the presence of hemodynamically important atherosclerosis as a significant risk factor for cerebro-vascular accident we need to consider the introduction of ultrasound scan as a routine test in the assessment of carotid arteries in patients who had completed radiotherapy to the head and neck area.

Longitudinal changes in the carotid arteries of head and neck cancer patients following radiation therapy: Results from a prospective serial imaging biomarker characterization study.

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer. METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated. RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; P = 0.014), which increased at 3 and 4 years (0.128 mm vs 0.013 mm, P = 0.016, and 0.177 mm vs 0.023 mm, P = 0.0002, respectively). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, -0.89, P = 0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility. CONCLUSIONS: Functional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.

Photobiomodulation for Blood Pressure and Heart Rate Reduction in Mastectomized Women on Hormone Blockers: A Randomized Controlled Trial.

Objective: To assess the impact of intravascular laser irradiation of blood (ILIB) on the primitive carotid artery (PCA) hemodynamic variables, specifically blood pressure (BP) and heart rate (HR), in mastectomized patients undergoing hormone blocker treatments. Materials and methods: This study is a controlled, experimental, and randomized clinical trial. Patients were allocated into two groups: the experimental group (G1)-patients who received ILIB therapy using a 660 nm laser targeted at the PCA, and the control group (G2)-patients who did not receive ILIB therapy. Clinical research was conducted weekly, with measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR. The Mann-Whitney U test for independent samples was used, with a significance level of α = 0.05. Results: Systemic photobiomodulation on the PCA did not demonstrate a statistically significant difference in relation to SBP and DBP. However, for HR, the p-value was <0.05, indicating a significant difference between G1 and G2. The initial mean p > decreased from 142.3 to 116.4 mmHg in G1, and from 130.4 to 119.8 mmHg in G2. The DBP varied from 78.8 to 72.8 mmHg in G1, and from 79.1 to 74.2 mmHg in G2. A statistically significant difference was observed in HR, decreasing from 81.3 to 62.06 bpm in G1, and changing minimally from 74.1 to 75.1 bpm in G2. A considerable reduction was present in the timing of application. Conclusions: ILIB therapy applied to the PCA induces a reduction in BP and, more notably, HR in mastectomized women using the tamoxifen or aromatase inhibitors.

Short-Term Statin Treatment Reduces, and Long-Term Statin Treatment Abolishes, Chronic Vascular Injury by Radiation Therapy.

BACKGROUND: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration. METHODS AND RESULTS: C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca2+ activated K+ BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes. CONCLUSIONS: Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.

Radiation-induced carotid stenotic lesions have a more stable phenotype than de novo atherosclerotic plaques.

OBJECTIVE: To identify plaque characteristics of carotid artery radiation-induced stenosis. MATERIALS AND METHODS: Nineteen carotid plaques were obtained during carotid endarterectomy (CEA) in 17 consecutive patients with prior cervical radiation therapy (XRT) (median interval 10 years) and compared with 95 matched control carotid plaques of patients without a history of XRT. The following histopathological factors were assessed: calcification, collagen, macrophages, smooth muscle cells, atheroma, microvessels and intraplaque haemorrhage. Association of individual histological parameters with XRT plaque was analysed through a multivariable regression model. RESULTS: Less infiltration of macrophages (6/19 versus 60/95, adjusted p = 0.003) and a smaller lipid core size (Atheroma >10%: 10/19 versus 80/95, adjusted p = 0.006) were independently associated with XRT plaque, compared to non-XRT plaques. CONCLUSIONS: Carotid stenotic lesions in patients with previous cervical radiation are less inflammatory and more fibrotic than carotid atherosclerotic lesions in non-radiated patients.

Carotid artery revascularisation following neck irradiation: immediate and long-term results.

OBJECTIVE: Carotid artery stenosis is a complication of neck irradiation. We describe the immediate and long-term results of surgical treatment. METHODS: This was a retrospective single centre study. From 1996 to 2009, 24 consecutive patients who had in the past received neck radiation therapy (mean 12 years, 1-41 years) underwent 27 primary carotid artery revascularisation procedures. Six patients (23%) had previous radical neck dissection, three permanent tracheostomies and one cervicoplasty with pectoral muscle flap. Indications for surgery included symptomatic (five transient ischaemic attacks (TIAs), four strokes; 34%) and asymptomatic (18 patients, 66%) stenosis. Four patients had occlusion of the contralateral carotid. General anaesthesia without shunting was used with measurement of stump pressure. Carotid interposition bypass grafting included 23 vein grafts and three polytetrafluoroethylene (PTFE) grafts. RESULTS: No perioperative deaths or central neurological events occurred. Three patients suffered transient cranial nerve injuries. Eleven patients died during follow-up, mean interval of 28 months (range 6-120 months), of causes unrelated to surgery. Five patients had recurrent bypass stenosis with one TIA and one stroke. All other surviving patients remained asymptomatic. CONCLUSION: Despite no comparative study as evidence, we think that the perioperative risk of stroke is at least comparable with the risk encountered for angioplasty procedures.

Sonographic assessment of acute changes in plaque size and echogenicity and in intima-media thickness of carotid arteries after neck radiation therapy.

BACKGROUND: Ultrasonic assessment of acute changes in carotid artery walls before and after neck radiation therapy (RT). METHODS: Fifty cancer patients scheduled for curative neck irradiation were included and underwent sonographic examination of carotid arteries, with assessment of intima-media thickness (IMT) and plaque size and echogenicity before and immediately after completion of RT. RESULTS: IMT was linearly correlated with age and before RT (r = 0.267, p = 0.007) and increased after RT (0.68 ± 0.11 versus 0.87 ± 0.16, p < 0.001), without correlation with total RT dose and protocol. New plaques (six hypoechoic, one hyperechoic, and one calcified) were found in eight patients after RT, while 17 of the 44 plaques that were present before RT increased in size, and 8 soft and 1 dense plaques in nine patients became calcified. CONCLUSIONS: Radiation in the acute phase not only increases the IMT but also causes new plaque formation and changes in plaque size and echogenicity.

Can carotid-sparing radiotherapy approaches replace with conventional techniques for the patients with T1 glottic larynx cancer?

OBJECTIVES: This study aims to compare the carotid artery doses applied with various radiotherapy techniques for the treatment of T1N0 glottic larynx cancer. PATIENTS AND METHODS: Five patients were simulated with using computed tomography (CT). Clinical (CTV) and planning target volumes (PTV) were created for T1N0 glottic larynx cancer. Planning risk volumes (PRV) were constructed for carotid arteries and spinal cord. Three irradiation planning, opposed lateral box field (OLBF), three dimension conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) were done for each patient. Over 95% of planned target volumes were loaded with predetermined dose (a total of 62.25 Gy of 2.25 Gy daily dose). RESULTS: The comparison of the treatment planning of five T1 glottic larynx cancer, three involving the right vocal cord and two involving the left vocal cord, the technique of IMRT planning was provided the best carotid-sparing doses. Mean carotid V35, V50, and V63 values including OLBF, 3DCRT, and IMRT were 70%, 47%, 35%; 55%, 15%, 5% and 28%, 6%, 0%, respectively. The statistical comparison of V35, V50 and V63 revealed significant values for OLBF and IMRT. Dose of spinal cord did not exceed 45 Gy for any of radiation treatment planning. Between the three techniques, there was no significant difference in terms of conformity index and dose distribution was homogenous with all techniques. CONCLUSION: It is obvious that IMRT planning technique can decrease the carotid artery radiation doses in early stage glottic larynx cancer.

Hemodynamic changes induced by preventive exposure to terahertz radiation at a frequency range corresponding to molecular emission and absorption spectrum of nitric oxide in animals under conditions of acute stress.

We studied the influence of preventive irradiation with terahertz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on hemodynamic parameters in arteries of albino rats upon acute immobilization stress. We showed that exposure to the specified frequencies can produce adaptogenic effect manifesting in the absence of post-stress changes in the linear, systolic, and diastolic blood flow velocities and pressure gradient in various blood vessels of experimental animals.

A Newly Designed Seed-Loading Device for Verifying the Safety of 125I Implants to the Canine Carotid Artery.

A seed-loading device was designed and modeled using the Monte Carlo method to verify the biological effect of iodine-125 (125I) particles on blood vessels through animal experiments. The dose distribution characteristics of irradiated vessels were established by adjusting the design variables and geometry. The deviation between the actual value and the theoretical value was verified in vitro by the thermoluminescence dosimetry (TLD) method. After verification, the device was used to examine the biological effect of 125I irradiation of canine carotid arteries in two dogs (and one control dog) for 180 days. The hollow cylinder seed-loading device was constructed with an inner diameter of 0.5 cm and a length of 3.3 cm. When six seeds were loaded into a single layer, the source strength ratio of the intermediate layer to the edge layer was 0.7:1. When six layers of seeds were arranged at 0.45-cm intervals, the deviations between the maximum, minimum and mean energy fluence within 2.25 cm of the vessel wall were 2.19% and -4.12%, respectively, and -9% and 4%, respectively, when verified in vitro using TLD. The carotid arteries showed good tolerance to 0.56 kGy (range of 0.51-0.58 kGy) after 180 days of irradiation. In conclusion, this 125I seed-loading device overcomes the random distribution of seeds and lays an accurate radiophysical foundation for subsequent biological experiments. The preliminary results showed that the carotid artery has good tolerance to 0.56 kGy irradiation.

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments.

PURPOSE: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized. METHODS AND MATERIALS: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed. RESULTS: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT. CONCLUSIONS: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.

Longitudinal atherosclerotic changes after radio(chemo)therapy of hypopharyngeal carcinoma.

BACKGROUND: Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up. METHODS: Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2 months to 4.5 years. For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records. RESULTS: Total plaque volume rose from 0.25 cm3 before to 0.33 cm3 after therapy but this was not significant (p = 0.26). The mean number of plaques increased from 5.7 to 8.1 (p = 0.002), and the intima media thickened from 1.17 mm to 1.35 mm (p = 0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter. CONCLUSION: Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear.

Preliminary Simulation Study of Carotid Artery and Pharyngeal Constrictor Muscle Sparing-Radiotherapy in Glottic Carcinoma.

BACKGROUND: This preliminary simulation study aimed to compare the dosimetric outcomes of carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) in patients with T1N0M0 glottic carcinoma undergoing helical tomotherapy-intensity modulated radiotherapy (HT-IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) plans. METHODS: In addition to the clinical target volume (CTV) which was defined as the entire larynx, the CAs and PCM of 11 glottic carcinoma patients were delineated. The CTV was uniformly expanded 5 mm to create a planning target volume (PTV) relative to the PCM and at a distance of 2 mm from the CA. The dosimetric characteristics in HT-IMRT and lateral opposed fields-based 3D-CRT plans were analyzed. RESULTS: Median D95%and V100% of PTV were significantly higher in HT-IMRT (p < 0.001) compared to 3D-CRT. The right/left CA dosimetric outcomes, including the mean doses (20.7/21.5 Gy versus 48.7/50.5 Gy), Dmax (53.6/52.0 Gy versus 67.4/67.7 Gy), V30 (25.0/27.1% versus 77.6/80.3%), V40 (8.0/7.9% versus 74.6/71.9%), and V50 (2.0/1.2% versus 70.0/71.6%) were also significantly lower in HT-IMRT (p < 0.05), similar to the mean PCM doses (49.6 Gy versus 62.6 Gy for 3D-CRT;p < 0.001), respectively. CONCLUSIONS: Our present results demonstrated the feasibility of simultaneous sparing of the CAs and PCM in HT-IMRT- compared to 3D-CRT plans in glottic carcinoma patients undergoing definitive radiotherapy.