Radiation-induced carotid artery atherosclerosis

Purpose

Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis.

Materials and methods

From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT.

Results

The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16–55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18–40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p = 0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p < 0.001 and <0.01, respectively).

Conclusions

The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups.     

Supraclavicular radiation for breast cancer does not increase the 10-year risk of stroke

BACKGROUND: Modern radiation techniques, which limit the radiation dose to the heart during treatment for breast cancer, have greatly reduced the risk of radiation-induced cardiac injury. However, the risk of radiation damage to the carotid artery, which is often incidentally included in the supraclavicular radiation field for breast cancer treatment, is not routinely examined, and the technique used to treat this field has not changed significantly from early radiation trials. The purpose of the current study was to compare the incidence of hospitalization for stroke among women with breast cancer treated with supraclavicular radiation with those who received radiation therapy to the breast but not the supraclavicular fossa. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database for 5752 women who were diagnosed with American Joint Committee on Cancer (AJCC) Stage I-III nonmetastatic breast cancer between 1988 and 1997 were analyzed. Women included were age > or = 66 years, had known lymph node (LN) status, had tumors measuring < or = 5 cm, underwent breast surgery, and received adjuvant radiation therapy (with or without supraclavicular irradiation). Patients with < 5 years of follow-up were excluded because events in the first 5 years after radiation were unlikely to be radiation induced. A Cox proportional hazards model was used to compare patients with 0 positive LNs (surrogate group for no supraclavicular radiation, n = 5281) with patients with > 4 positive LNs (surrogate for supraclavicular radiation group, n = 471) for the endpoint of hospitalization for stroke. Time-to-event curves were calculated using the conditional Kaplan-Meier method. RESULTS: The median follow-up for the 0 and 4+ LN cohorts were 92 months and 90 months, respectively (minimum of 60 months). The 10-year and 15-year actuarial freedom from hospitalization for stroke was 91% (0 LN) versus 89.5% (4+ LN) and 79% (0 LN) versus 81.6% (4+ LN), respectively (P = .28). Estrogen receptor status was balanced between the 2 cohorts. As expected, the 4+ cohort had more advanced tumors, higher stage, larger tumor size, and higher grade (P < .0001). In multivariate analysis including LN group, year of diagnosis, age, race, type of surgery, stage, tumor size, grade, estrogen receptor status, and Charlson comorbidity score, only increased age (hazard ratio [HR] for ages 70-74 years, 1.6; HR for ages 75-79 years, 2.1; and HR for age 80 + years, 2.7) and increasing comorbidity score were predictive of an increased risk of hospitalization for stroke. CONCLUSIONS: Although patients with nonbreast malignancies treated with higher doses to the carotid arteries have been shown to have an increased risk of carotid injury, no evidence was found that radiation to the carotid delivered during supraclavicular irradiation for breast cancer increases the risk of hospitalization for stroke.     

Therapy of cancer patients with concurrent critical atherosclerosis of the aorta and peripheral arteries

The results are presented of 5-year experience with therapy of concurrent neoplasia and atherosclerotic lesions of the aorta and peripheral arteries gained at the Center for Oncosurgery, Regional Oncological Dispensary, Chelyabinsk. The analysis was concerned with the treatment received by 118 patients, irrespective of tumor stage or localization: surgical correction of blood flow was carried out in 60. Clinically significant atherosclerotic lesions of the aorta and peripheral arteries in a cancer patient should not be regarded as absolute or relative contraindication for combined treatment. Atherosclerotic occlusion of the femoral or shin arteries was managed conservatively in most cases (p<0.05). In cases of similar lesions of the carotid arteries and aortal aneurysm, surgical correction of blood flow was mostly used.     

Rupture of major vessels after radiation.

Rupture of irradiated large vessels is an uncommon complication which tends to occur in carotid, aorta, and femoral arteries, in decreasing order of incidence. It particularly affects men subjected to surgery and radiotherapy for epidermoid carcinomas in oropharynx, esophagus, or genitalia. Contrary to some opinion, radiation is not the most significant cause; this "spontaneous" arterial rupture can occur without radiation. The perforation is not associated with tumor invasion of arterial wall, as has been claimed. Surgical complications, especially necrosis of skin flaps, infection, and fistulas are most important etiologically. Only 2 of the 11 instances that we describe appear to have been caused mainly by radiation. The perforation is usually fatal, but several patients, including 3 of our series (2 carotid, 1 femoral), have been saved by hospital personnel aware of this complication. To prevent it, prolonged exposure or infection of arteries, whether irradiated or not, should be avoided.     

颈动脉体瘤的DSA诊断

目的加深对颈动脉体瘤 DSA 表现特点的认识,探讨其诊断与介入治疗价值。方法由两名有经验的放射学医师按双盲法对12例动脉体瘤的 DSA 造影资料进行回顾性分析,然后共同讨论并达成一致意见。结果 DSA 均能明确诊断。所有患者均见颈动脉分叉角度增大,颈内、外动脉移位;大部分瘤体以颈外动脉供血为主,血供较丰富; 6例患者瘤体包绕颈动脉者可见局部血管受侵。2例患者栓塞后造影见肿瘤染色范围缩小,且术中出血明显减少。结论 DSA 是颈动脉体瘤的诊断和术前评估的有效手段。术前栓塞有利于减少术中出血。     

颈动脉体瘤的DSA诊断

目的 加深对颈动脉体瘤DSA表现特点的认识，探讨其诊断与介入治疗价值。方法 由两名有经验的放射学医师按双盲法对12例动脉体瘤的DSA造影资料进行回顾性分析，然后共同讨论并达成一致意见。结果 DSA均能明确诊断。所有患者均见颈动脉分叉角度增大，颈内、外动脉移位；大部分瘤体以颈外动脉供血为主，血供较丰富；6例患者瘤体包绕颈动脉者可见局部血管受侵。2例患者栓塞后造影见肿瘤染色范围缩小，且术中出血明显减少。结论 DSA是颈动脉体瘤的诊断和术前评估的有效手段。术前栓塞有利于减少术中出血。     

Late Radiation-Induced Carotid Artery Stenosis and Stroke in Pediatric Patient Treated With Proton Radiation Therapy for Skull-Base Chordoma

Radiation vasculopathy is a well-recognized late complication of radiation therapy. We present a case of a stroke 29 years after high-dose proton radiation therapy for skull-base chordoma due to occlusion of bilateral internal carotid arteries.     

放射增敏治疗的靶基因

对放、化疗的耐受是癌症治疗的主要障碍 ,基因治疗联合放疗代表了癌症治疗的一种新方式。采用基因治疗方式提高肿瘤细胞对射线的敏感性 ,然后联合放疗以提高治疗效果 ,在动物和临床试验中已取得显著效果。就放射增敏治疗的靶基因及其实验和临床研究进展予以综述。     

Usefulness of CT-angiography for superselective intra-arterial chemotherapy for advanced head and neck cancers

Eighteen N3 cases, fourteen skullbase invasion cases and twenty-six cases of paranasal sinus cancer with orbital invasion were treated by superselective intra-arterial chemotherapy using CDDP and sodium thiosulfate to preserve the organs and to improve poor prognosis. In these patients, 100-150 mg/m2 of CDDP was administered weekly to each feeding artery of the tumor superselectively at 5 mg/m. CT-arteriography (CTA) was used to diagnosis all feeding arteries of advanced cancers before infusing CDDP. Twenty-three of 26 cases with orbital invasion were treated with preservation of the eyeball. In three cases with extirpation of the eyeball CTA was not used in the treatment, and CDDP was infused into only the maxillary artery excluding the transverse facial artery. In skullbase invasion cases, the number of complete responses (CR) was 8/14, and that of partial responses (PR) was 6/14. Feeding arteries originating from the external carotid artery were found in 10 of all 14 cases by CTA, and four cases in which blood supply was from both carotid arteries were all anterior skullbase invasion cases. Ten cases with superselective intra-arterial chemotherapy originating from only the external carotid artery were significantly better responders than four cases originating from both carotid arteries. In N3 cases, feeding arteries were found in more than three arteries by CTA and the overall survival rate was 55%, calculated by the Kaplan-Meier method. CTA is a very efficient method for diagnosing all feeding arteries of advanced cancers in the superselective intra-arterial chemotherapy.     

CT and duplex scanning: a comparison of imaging techniques for evaluation of the carotid tree in head and neck cancer patients

Carotid artery disease is a common condition which, like head and neck cancer, is primarily smoking related. Internal carotid stenosis may result in cerebro-vascular complications, while severe stenosis of the external carotid can potentially compromise microvascular free tissue transfer reconstruction. We were interested to see whether any co-existing carotid artery disease could be assessed on the neck CT scan by comparing it to definitive duplex scanning in head and neck cancer patients. CT and duplex scanning of the common, internal and external carotid arteries was compared in 30 patients (180 vessels). The arterial phase of the neck CT scans were reviewed by two radiologists and all duplex scans were performed by one vascular technician to minimise inter-operator variability. The respective findings were blinded. Significant correlations were found between CT and duplex in confirming stenosis of the common and internal carotid arteries (P<0.001). There was a weak correlation between CT and duplex in the assessment of the external carotid system (P=0.02 and P=0.08), with CT under-estimating the true extent of stenosis in this vessel. The sensitivity and specificity of CT compared to duplex was 77% and 94% respectively. CT is useful not only for imaging the neck of head and neck cancer patients, but also in screening for carotid stenosis. Duplex scanning is more accurate than CT in assessing the external artery, and is useful for evaluating patients with significant stenosis of the carotid tree.     

The effect of irreversible electroporation on blood vessels

We present a pilot study on the long term effects of irreversible electroporation (IRE) on a large blood vessel. The study was motivated by the anticipated use of IRE for treatment of cancer tumors abutting large blood vessels. A sequence of 10 direct current IRE pulses of 3800 V/cm, 100 micros each, at a frequency of 10 pulses per second, were applied directly to the carotid artery in six rats. Measuring tissue conductivity during the procedure showed, as predicted, an increase in conductivity during the application of the pulse, which suggests that this measurement can be used to control the application of IRE. All the animals survived the procedure and showed no side effects. Histology performed 28 days after the procedure showed that the connective matrix of the blood vessels remained intact and the number of vascular smooth muscle cells (VSMC) in the arterial wall decreased with no evidence of aneurysm, thrombus formation or necrosis. Average VSMC density was significantly lower following IRE ablation compared with control (24 +/- 11 vs. 139 +/- 14, P<0.001), with no apparent damage to extra cellular matrix components and structure. In addition to the relevance of this study to treatment of cancer near large blood vessels these findings tentatively suggest that IRE has possible applications to treatment of pathological processes in which it is desired to reduce the proliferation of VSMC population, such as restenosis and for attenuating atherosclerotic processes in clinical important locations such as coronary, carotid and renal arteries.     

Combined radiation therapy and chemotherapy for carcinoma of the cervix

Cervical cancer is the third most common cancer affecting women worldwide. Surgery, radiation therapy, and chemotherapy have been used in various settings in an effort to improve survival rates of patients with cervical cancer. Recent cooperative clinical trials have demonstrated a benefit from the concurrent use of chemotherapy and radiation therapy to treat cervical cancer. These studies have provided the most significant improvement in the treatment of locally advanced disease in more than 30 years. This review summarizes studies of sequential and concurrent combinations of chemotherapy and radiation therapy for the treatment of cervical cancer, as well as the recent controversies related to this treatment.     

阴道放射性损伤研究进展

放疗是宫颈癌的重要治疗手段,局部晚期宫颈癌的治疗主要依赖体外放疗和腔内后装放疗。宫颈癌放疗过程中,阴道既是治疗的靶器官,也是重要的危及器官,当其受到较高辐射剂量时,必定会发生放射性损伤。阴道放射性损伤及其所致的性功能障碍成为宫颈癌幸存者长期困扰的重要问题。本文将对近几年有关阴道剂量学和阴道放射性损伤的相关研究进行总结归纳,探究其病理变化、临床表现及诊治预防。     

Hyperthermia: a potent enhancer of radiotherapy

Hyperthermia is generally regarded as an experimental treatment with no realistic future in clinical cancer therapy. This is totally wrong. Although the role of hyperthermia alone as a cancer treatment may be limited, there is extensive pre-clinical data showing that in combination with radiation it is one of the most effective radiation sensitisers known. Moreover, there are a number of large randomised clinical trials in a variety of tumour types that clearly show the potential of hyperthermia to significantly improve both local tumour control and survival after radiation therapy, without a significant increase in side-effects. Here we review the pre-clinical rationale for combining hyperthermia with radiation, and summarise the clinical data showing its efficacy.     

The effect of external electron beam on neointima in rat carotid artery injury model.

PURPOSE: Endovascular irradiation with either a gamma or a beta source has shown to reduce neointimal proliferation. However, the effect of external-beam radiation on neointimal hyperplasia is controversial. The objective of this study was to determine the effect of external-beam irradiation with different doses on neointimal hyperplasia in the rat carotid artery injury model. METHODS AND MATERIALS: Twenty-seven Sprague-Dawley rats underwent endothelial denudation injury by 2F Fogarty balloons on carotid artery. Immediately after the injury, rats were irradiated externally using 6-MeV electrons. Rats were grouped according to the radiation doses, 0 Gy as controls (n = 5), 5 Gy (n = 5), 10 Gy (n = 5), 15 Gy (n = 6), and 20 Gy (n = 6). Then, rats were sacrificed after 2 weeks and the carotid arteries were perfusion-fixed in paraformaldehyde. External elastic lamina (EEL) area, lumen area, maximal intimal thickness (MIT), and intimal area (IA) of the injured segments were measured on the basis of histomorphometry. RESULTS: In EEL and lumen area, there was no statistically significant difference between the irradiated groups and the controls. In MIT and IA, low-dose radiation (5 Gy and 10 Gy) did not induce any significant reduction. High-dose radiation (15 Gy and 20 Gy), however, reduced MIT and IA significantly. CONCLUSION: External electron beam reduced the intimal area, and the inhibition of neointimal proliferation was dependent upon radiation doses. This study suggests that the minimal effective dose for the inhibition of neointimal hyperplasia following denudation injury in the rat carotid model is between 10 Gy and 15 Gy.     

Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy.

BACKGROUND: Radiation-induced carotid stenosis in patients with head and neck tumors can cause significant mortality and morbidity. This study examined the incidence of stenosis in the extracranial carotid arteries of nasopharyngeal carcinoma patients after radiotherapy. METHODS: The extracranial carotid arteries of 71 (53 male and 18 female; mean age of 53.6 years) postradiation patients with nasopharyngeal carcinoma were examined with color Doppler ultrasound. The distribution of the arterial stenosis and the degree of stenosis were documented. The results were compared with the control group, which comprised 51 newly diagnosed nasopharyngeal carcinoma patients (35 male and 16 female, mean age of 48.8 years) before radiotherapy. Incidences of risk factors for arterial stenosis such as hypertension, smoking, and hypercholesterolemia also were studied in these two groups. RESULTS: There was no significant difference in the incidence of risk factors between the two groups. Arterial stenosis was, however, more common in the postradiation group than the preradiation group (56 of 71 vs. 11 of 51). The common/internal carotid arteries (CCA/ICA) were most commonly involved (55 of 71 vs. 11 of 51; P < 0.01), followed by the external carotid artery (ECA) (32 of 71 vs. 1 of 51; P < 0.01) and vertebral artery (VA; 5 of 71 vs. 0; P = 0.069). Significant stenosis (> 50% reduction of luminal diameter) was only found in the postradiation group (21 of 71 in CCA/ICA, 11 of 71 in ECA, 4 of 71 in VA). CONCLUSIONS: This study showed that radiation could cause significant carotid stenosis. Ultrasound examinations for these patients therefore are necessary for early detection and possible intervention of this late radiation-induced complication.     

Hypofractionated radiation therapy for prostate cancer: risks and potential benefits in a fiscally conservative health care system

Prostate cancer is the second most common cause of cancer death in American men and represents a significant factor in US health care costs. Radiation therapy serves as one of the most effective treatments for prostate cancer. However, radiation is also an expensive treatment modality and is a significant contributor to the overall rise in the cost of prostate cancer care. Currently, standard external beam radiation therapy for prostate cancer consists of between 75.6 and 81.0 Gy of radiation separated into 1.8- to 2-Gy doses (or "fractions") given daily for between 7 and 9 weeks. Recently, relatively shorter treatment schedules delivering more radiation per treatment-consisting of fractions > 2 Gy-over shorter time periods have been proposed in an effort to curtail rising health care costs and improve patient convenience. However, significant uncertainty still remains regarding outcomes from this type of more condensed treatment, known as"hypofractionated"radiation. In this article, we provide the historical background and rationale for hypofractionated prostate cancer treatment, discuss the potential benefits and risks of prostate hypofractionation, and review the clinical evidence regarding the effectiveness of hypofractionated radiation therapy for prostate cancer.     

Cardiovascular effects of radiation therapy

Radiation therapy (RT) plays a prominent role in the treatment of many cancers. With increasing use of RT and high overall survival rates, the risks associated with RT must be carefully considered. Of these risks, the cardiovascular and autonomic toxicities have been of significant concern. In fact, cardiovascular disease is the leading cause of nonmalignancy-related death in cancer survivors.The manifestations of radiation induced cardiac injury include the acute toxicities of myopericarditis and late toxicities including constrictive pericarditis, restrictive cardiomyopathy, coronary artery disease, valvular heart disease, heart failure, and conduction abnormalities. Neck and cranial RT have also been associated with significant long-term toxicities including accelerated occlusive carotid artery disease, autonomic dysfunction due to baroreceptor damage, and development of metabolic syndromes due to damage to the hypothalamic-pituitary axis.The clinical manifestations of radiation induced disease may not present until several years following the delivery of radiation. We review the adverse effects of RT on these organ systems and discuss risk reduction strategies that may effectively mitigate some of these adverse outcomes.     

Management of paranasal sinus malignancy

Opinion statement Malignancies of the nasal cavity and paranasal sinuses represent a wide spectrum of histologies, tissues of origin, and anatomic primary sites. The inherent difficulty in generalizing treatment approaches is obvious, given the numerous variables associated with the broadly-based term, paranasal sinus malignancy (PNSCa). Nevertheless, the majority of epithelial and salivary malignancies of this region (ie, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, sinonasal undifferentiated carcinoma, and esthesioneuroblastoma) require surgical intervention as part of any treatment regimen. Recent trends have broadened the indications for chemotherapeutic and radiotherapeutic options in the management of advanced PNSCa. Nonepithelial malignancies, including the wide variety of sarcomas arising in this region, most commonly require multimodality treatment including chemotherapy, radiation, and/or surgery for definitive treatment. Moreover, the proximity of the nasal cavity and paranasal sinuses to structures including the orbit, dura, brain, cranial nerves, and carotid arteries mandates careful radiologic and neurologic evaluations throughout the course of the disease. Surgical advances now permit complex tumor removal and reconstruction surrounding these structures resulting in functional and cosmetic improvements when compared to earlier techniques. However, additional clinical trials are necessary to systematically evaluate the locoregional control, organ-preservation strategies, and survival related to the variety of treatments currently available.