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.

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.

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.

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.

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.

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.

Medical prevention and treatment of radiation-induced carotid injury.

Radiotherapy has significantly improved the survival of cancer patients but is also associated with several adversities, including radiation-induced carotid injury (RICI). The RICI mechanisms are complex, including vessel inflammatory injury, carotid atherosclerosis, intimal proliferation, media necrosis, and peri-adventitial fibrosis. The main manifestation and adverse consequence of RICI is carotid artery stenosis (CAS), which can lead to stroke and transient ischemic attack. Currently, carotid artery injury is primarily diagnosed via color-coded duplex sonography. Early detection of traumatic changes in the carotid artery depends on measurements of carotid intima-media thickness; serum biomarker testing also shows great potential. CAS is mainly treated with carotid endarterectomy or carotid angioplasty and stent implantation. Notably, bone marrow mesenchymal stem cells are advantageous in RICI treatment and reduce carotid inflammation, oxidative stress, and delaying atherosclerosis. This review summarizes the mechanisms, examination methods, and latest treatments for RICI to provide data for its clinical prevention and treatment.

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.

Re-irradiation with protons or heavy ions with focus on head and neck, skull base and brain malignancies.

Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors. High life time doses nonetheless lead to a different scope of side-effects, e.g. an enhanced rate of carotid blow outs has been reported. This review summarizes the current data on particle irradiation of the aforementioned locations and malignancies.

Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease.

Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.

Chemoradiation and local recurrence of head and neck squamous cell carcinoma and the risk of carotid artery blowout.

BACKGROUND: Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted. METHODS: In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection. RESULTS: Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P < .0001). Cox regression for forward selection revealed local recurrence (hazard ratio [HR], 1.9; P < .0001), T status (HR, 1.9; P = .03), and CRT (HR, 2.0; P < .0001) as independent risk factors for mortality related to CBS. CONCLUSION: CBS is a rare event in patients with HNSCC demonstrating reduced OS/RFS. Advanced T status, C/RT, and the recurrence of local tumors increase the risk of CBS-associated death.

Carotid stenosis prevalence after radiotherapy in nasopharyngeal carcinoma: A meta-analysis.

PURPOSE: Radiotherapy (RT) is the most effective treatment for nasopharyngeal carcinoma (NPC) but may cause stenosis of the carotid arteries. This meta-analysis evaluates the prevalence of carotid stenosis after radiation therapy. MATERIALS AND METHODS: Online search for studies reporting carotid stenosis in patients with NPC who received radiation therapy (RT) compared to NPC patients who did not receive RT and compared to healthy controls. RESULTS: Twelve studies were included for a total analysis of 1928 patients (837 received RT and 1091 were controls). RT patients showed a statistically significant higher incidence of overall stenosis (pooled risk ratio = 4.17 [2.44, 7.10], p < 0.00001) and an even greater incidence of significant stenosis (50% or more) (pooled risk ratio = 8.72 [3.53, 21.55], p < 0.00001). Analyzing by individual blood vessels showed that the RT patients had significantly higher incidence of stenosis in common carotid artery (CCA), external carotid artery (ECA), carotid bulb, CCA and internal carotid artery (ICA), and CCA/ICA/carotid bulb. CONCLUSIONS: NPC patients who receive RT have increased risk of developing carotid stenosis, and should be screened after treatment.

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.

Fitting NTCP models to SBRT dose and carotid blowout syndrome data.

PURPOSE: To estimate the radiobiological parameters of three popular NTCP models, which describe the dose-response relations of carotid blowout syndrome (CBOS) after stereotactic body radiotherapy (SBRT). To evaluate the goodness-of-fit and the correlation of those models with CBOS. METHODS: The study included 61 patients with inoperable locally recurrent head and neck cancer treated with SBRT using CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey between June 2007 and March 2011. The dose-volume histograms of the internal carotid were exported from the plans of all the patients. The follow-up results regarding the end point of carotid blowout syndrome were collected retrospectively. Initially, univariable analyses (Wilcoxon rank-sum or Chi-square tests) and a multivariate logistic regression analysis were performed between the outcome data and a list of clinical and treatment factors to identify significant correlations. Additionally, the Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC), and Odds Ratio methods. RESULTS: The clinical/treatment factors that were found to have a significant or close to significant correlations with acute CBOS were Age at the time of CK (P-value = 0.03), Maximum carotid dose (P-value = 0.06), and CK prescription dose (P-value = 0.08). Using Dmax , physical DVH, and EQD2 Gy -DVH as the dosimetric metrics in the NTCP models, the derived LKB model parameters were: (a) D50  = 45.8 Gy, m = 0.24, n = n/a; (b) D50  = 44.8 Gy, m = 0.28, n = 0.01; and (c) D50  = 115.8 Gy, m = 0.45, n = 0.01, respectively. The AUC values for the dosimetric metrics were 0.70, 0.68, and 0.61, respectively. The differences in AIC between the different models were less than 2 and ranged within ±0.9. CONCLUSION: The maximum dose to the internal carotid less than 34 Gy appears to significantly reduce the risk for CBOS. Age at the time of CK, Maximum carotid dose, and CK prescription dose were also found to correlate with CBOS. The values of the parameters of three NTCP models were determined for this endpoint. A threshold of gEUD <34.5 Gy appears to be significantly associated with lower risks of CBOS.

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.

Carotid Dosimetry and the Risk of Carotid Blowout Syndrome After Reirradiation With Head and Neck Stereotactic Body Radiation Therapy.

PURPOSE: To correlate carotid dose and risk of carotid blowout syndrome (CBOS) after stereotactic body radiation therapy (SBRT), hypothesizing that carotid dose does not correlate with CBOS. METHODS AND MATERIALS: We retrospectively reviewed 186 patients with recurrent, previously irradiated head and neck cancer treated between January 2008 and March 2013. Patients treated early in our experience with incomplete dosimetry were excluded from analysis (n = 111). A total of 75 patients were identified, providing 150 carotid arteries for analysis. Median follow-up was 8 months (range, 1-91 months) for all patients, and 37 months for surviving patients (range, 31-91 months). Patients were treated with linear accelerator-based SBRT to a median dose up to 44 Gy (range, 40-50 Gy) in 5 fractions delivered on a twice-weekly basis. Concurrent cetuximab was used in 63 patients (84%). The bilateral common, internal, and external carotid arteries were delineated 2 cm above and below the planning target volume. The maximum dose to 0.1 cm3 (D0.1cc), 1 cm3 (D1cc), and 2 cm3 (D2cc) of the carotid and the mean carotid dose from SBRT were recorded and analyzed for association with carotid bleeding events, using binary logistic regression. RESULTS: Median reirradiation interval was 20 months (range, 3-423 months), and median prior radiation dose was 70 Gy (range, 52.5-140 Gy). Sixteen patients (21.3%) received more than 1 course of SBRT, and the cumulative carotid doses from fused summary plans were recorded. The overall median D0.1cc, D1cc, D2cc, and mean carotid doses were 40.8 Gy (interquartile range [IQR], 21.6-47.6 Gy), 26.8 Gy (IQR, 14.1-42.1 Gy), 15.4 Gy (IQR, 8.4-32.7 Gy), and 15.0 Gy (IQR, 8.9-23.3 Gy), respectively. There were a total of 4 bleeding events (5.3%): 2 patients (2.7%) had mucosal bleeds that resolved after embolization of carotid branches, and 2 patients (2.7%) died from complications of CBOS. In the 2 patients with CBOS the D0.1cc was 48.4 Gy and 47.6 Gy, respectively. There was no significant association between bleeding events and D1cc (P = .280), D2cc (P = .571), or mean dose (P = .568). There was a trend toward increased risk of bleeding and D0.1cc (P = .080). CONCLUSIONS: These results demonstrate a low risk of bleeding after reirradiation with SBRT when 5 fractions are delivered on nonconsecutive days, even when tumor is completely encasing the carotid artery. Although limited by the low number of events, no significant association was found between dose-volume parameters and the risk of carotid bleeding. No CBOS was noted when D0.1cc was <47.6 Gy.

The evaluation of the feasibility of carotid sparing intensity modulated radiation therapy technique for comprehensive breast irradiation.

PURPOSE: To investigate the feasibility of carotid sparing intensity modulated radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries for comprehensive irradiation of breast cancer patients who have risk factors for atherosclerosis. The dose distribution of CS-IMRT technique and the conventional irradiation technique were also compared. PATIENTS AND METHODS: Ten patients who were previously treated with comprehensive three-dimensional conformal radiation therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans were compared in terms of conformity index, homogeneity index, and the doses to organ at risk and carotid arteries. RESULTS: The homogeneity and conformity indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the carotid arteries were reduced by applying CS-IMRT without compromising the target volume coverage. When the carotid artery was considered as organ at risk for CS-IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT plans (p=0.017). The median of the maximum dose to the carotid artery was decreased under 50Gy with CS-IMRT. CONCLUSIONS: CS-IMRT can significantly reduce the unnecessary radiation dose to the carotid arteries compared with conventional 3DCRT technique while maintaining target volume coverage. CS-IMRT technique can be considered for breast cancer patient with high risk of atherosclerosis.

Cardiovascular effects of radiotherapy on the patient with cancer.

The incidence of cancer (CA) has increased globally and radiotherapy (RT) is a vital component in its treatment. Cardiovascular injuries induced by RT in the treatment of thoracic and cervical CA have been causing problems in clinical practice for decades, and are among the most serious adverse effects of radiation experienced by the growing number of cancer survivors. This article presentes a review on the Lilacs, Scielo and Pubmed databases of the main cardiovascular injuries, their mechanisms, clinical presentations, treatments and prevention proposals. Injuries caused by RT include diseases of the pericardium, coronary artery disease, valvular disease, myocardial disease with systolic and diastolic dysfunction, conduction disorders, and carotid artery and great vessels disease. Thoracic and cervical irradiation increases cardiovascular morbidity and mortality. Despite the great progress in the improvement of RT techniques, totally excluding prime areas of the cardiovascular system from the irradiation field is not yet possible. Guidelines must be created for monitoring, diagnosis and treatment of patients with CA treated with RT.

Plaque Neovascularization Is Increased in Human Carotid Atherosclerosis Related to Prior Neck Radiotherapy: A Contrast-Enhanced Ultrasound Study.

OBJECTIVES: The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries. BACKGROUND: Exposure of the carotid arteries to RT during treatment for head and neck cancer is associated with increased risk for stroke. However, the effect of RT on IPN, a precursor to intraplaque hemorrhage and thus associated with plaque vulnerability, is unknown. METHODS: In this cross-sectional study, patients who had undergone unilateral RT for head and neck cancer ≥2 years previously underwent B-mode and contrast-enhanced ultrasound of both RT-side and non-RT-side carotid arteries. Presence of IPN during contrast-enhanced ultrasound was judged semiquantitatively as grade 0 (absent), grade 1 (present but limited to plaque base), or grade 2 (extensive and noted within plaque body). RESULTS: Of 49 patients studied, 38 (78%) had plaques. The number of plaques was significantly greater in the RT than the non-RT arteries. Overall, 48 of 64 RT-side plaques (75%) had IPN compared with 9 of 23 non-RT-side (39%) plaques (p = 0.002). Among patients with plaques, IPN was present in 81% of patients with RT-side plaques and 41% of patients with non-RT-side plaques (p = 0.004). Grade 0 IPN was significantly more common in patients with non-RT-side plaques (25% vs. 61%; p = 0.002), whereas grade 2 plaques were more common on the RT side (31% vs. 9%; p = 0.03). The only clinical variable that predicted the presence or absence of IPN was RT laterality. CONCLUSIONS: This is the first study in humans to reveal a significant association between RT and the presence and extent of IPN. This may provide insights into the mechanisms underlying the increased stroke risk among survivors of head and neck cancer treated by RT.