Heart and Blood Diseases

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Wounds and Injuries

Atherosclerosis

Breast Neoplasms

Congenital Abnormalities

Carotid Artery Diseases

Abnormalities, Radiation-Induced

Breast Diseases

Skin Diseases

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Radiation Injuries

carotid intima-media thickening ultrasound

Arik Tzukert, DMD

Hadas Lemberg, PhD

Amichay Meirovitz, MD

Radiation induced accelerated atherosclerosis is a well known entity that occurs in different regions, according to the therapy delivered.It is usually begins to be clinically evident several years after the radiation incident, as there is sufficient functional reserve to these vessels.Our proposal is aimed to better characterize this side effect. For that purpose, we have chosen to study women who received radiation to the breast, in which part of the carotid in the irradiated side was in the high energy radiation field. We will use Intima Media Thickening ultrasound to study the pattern of atherosclerosis plaque formation in radiated carotid arteries as compared to non-irradiated carotid arteries in women who are receiving radiation therapy for breast cancer.

Radiation induced atherosclerosis in Breast Cancer patients

Radiation induced accelerated atherosclerosis is a well known entity that occurs in different regions, according to the therapy delivered. This process takes a couple of years to develop. Therefore, the most affected populations are the long term survivors of potentially curative cancers such as Hodgkins lymphoma 1, 2, head and neck cancers 3-6, pelvic cancers (both prostate cancer and cervical cancer) 7, and breast cancer8-14. The mechanism of damage is thought to be direct endothelial damage, which is most significant about 6 months post XRT, followed by inflammation, cholesterol plaque formation and intimal thickening. This cascade, as well as the pathological findings, are similar to what is seen in natively occurring AS. However, in the post XRT setup, it is not limited to one part of the artery and usually encompasses the entire circumference of the radiated segment15-17.

The accelerated atherosclerosis resulting from radiation usually begins to be clinically evident several years after the radiation incident, as there is sufficient functional reserve to these vessels. However, changes can be seen much sooner, and some studies have shown significant changes as soon as one year after the initial insult 2, 18.

Literature reports suggest as high as 77.5% of symptomatic carotid stenosis (on risky regions of common carotid and internal carotid arteries) as compared to 21.6% on the matched control group (consisting of newly diagnosed patients with similar risk factors)18. A retrospective review from Philadelphia on 413 treated patients found RR for stroke of 2, as compared with the general population (matched for risk factors) from the Stockholm database5. Data from the Netherlands suggested risk for stroke as high as 5 times as compared to the matched group without cancer. The analysis was done on patients who received the treatment before 60 yo (the comparison was not made to the general population as these patient are usually smokers and drinkers and are usually at a higher risk to begin with, however XRT increases this already high risk by 5).

A new emerging technique of Carotid Intima-Media Thickening (IMT) has demonstrated the impact of radiation (2.2 Vs 0.7mm in controls)6.

Our proposal is aimed to better characterize this side effect. For that purpose, we have chosen to study women who received radiation to the breast, in which part of the carotid in the irradiated side was in the high energy radiation field. The contralateral artery, which received only trace of scattered radiation, can serve as the internal control. This is not the case in head and neck patients, who usually receive a high dose of radiation to both sides of the neck. The number of early breast cancer patients who received adjuvant radiation is relatively high, a factor which may help us reach the accrual goal much faster. Subsequently we are planning to proceed in a consecutive study and to try to pharmacologically interfere with progression of the AS, and perhaps even prevent it.

Intima Media Thickening US is a non-invasive US technique that is available at Hadassah University Medical Center and will be performed in this study in order to detect the degree of AS in affected and non affected arteries.

The suggested study will consist of two populations. Group 1 are women who received radiation for breast cancer in the past at various time intervals and the Group 2 are women with newly diagnosed breast cancer.

Markers and biochemistry tests that might elucidate predisposing and contributing factors for developing AS will also be done and analyzed on all patients. The latter could be a target for treatment and a surrogate to the treatment efficacy, side effects, and cancer progression (i.e. cholesterol levels, hypertension, hypothyroidism, etc.)

Radiation Induced Atherosclerosis in Breast Cancer Patients

Hadassah Medical Organization

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Nasopharyngeal Carcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Cerebrovascular Disorders

Brain Diseases

Central Nervous System Diseases

Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Ethanol

patients diagnosed as non-metastatic nasopharyngeal carcinoma who received definitive IMRT more than 3 years ago

untreated patients diagnosed as non-metastatic nasopharyngeal carcinoma

IMT measurements were performed using ultrasound machine in the pre-radiation and the post-radiation group. IMT was assessed at the common carotid artery (CCA) and the internal carotid artery (ICA) of both the left and right side.

Measurement of intima media thickness of carotid artery

Detection and measurement of plaques within internal carotid artery and common carotid artery by ultrasound

Detection and measurement of carotid plaques

Velocity measurement of carotid artery to determine carotid stenosis

Carotid Color Flow Duplex Testing

Montreal Cognitive Assessment

Cardiovascular risk factors include smoking, alcohol consumption, hypertension, diabetes mellitus, hypercholesterolemia, obesity. Cardiovascular diseases include ischemic stroke, ischemic coronary heart disease, TIA, etc.

Medical history of cardiovascular risk factors and cardiovascular diseases

Xiaomin Ou, MD

Xiayun He, MD

Radiation-associated carotid vasculopathy is a common late sequelae in patients with head and neck cancer, which correlates with the incidence of stroke. Currently, little is known about the incidence of radiation-associated carotid vasculopahty in the context of intensity-modulated radiation therapy (IMRT).

The aim of this study is to determine whether IMRT will increase the incidence of carotid vasculopathy in patients with nasopharyngeal carcinoma (NPC).

Radiation-associated Carotid Artery Disease in Patients With Nasopharyngeal Carcinoma

The Clinical Study of Radiation-associated Carotid Artery Disease in Patients With Nasopharyngeal Carcinoma Treated by IMRT

the intima media thickness of common carotid artery, internal carotid artery of the left or right side

Carotid stenosis is defined as the axial diameter of the carotid lumina decreases more than 50%.

Carotid plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness \>1.5 mm as measured from the media-adventitia interface to the intima- lumen interface.

the higher the number, the better the cognitive function

Fudan University

Principal Investigator, Clinical Professor

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Heart Diseases

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Ischemia

Evelyn Talbott

To investigate whether women with Polycystic Ovary syndrome (PCOS) have evidence of an increased prevalence rate of subclinical atherosclerosis as measured by the presence of plaque, increased intima-medial carotid artery wall thickness and lower brachial artery flow mediated vasodilation.

BACKGROUND:

The risk of coronary heart disease (CHD) is lower in women than men. This has been attributed to differences in sex hormones, insulin sensitivity, and environmental factors. Women with Polycystic Ovary syndrome have characteristics, including anovulation, hyperandrogenism and insulin resistance, which suggests a male risk factor profile. The study tests the hypothesis that women with PCOS are at greater risk of coronary heart disease than non-PCOS women. When the study was initiated in 1991, there were few data available on long-term followup of women with PCOS.

DESIGN NARRATIVE:

Beginning in 1991, the investigators tested the hypothesis that women with PCOS, who comprise 5 percent of the female population, are at greater risk of coronary heart disease than non-PCOS women. They traced and followed-up, via telephone interviews, 244 women with PCOS and 244 age-matched neighborhood controls. They then conducted a cross-sectional study to assess reproductive, hormonal and other coronary heart disease risk factors in the women with PCOS compared with the controls. Evaluation consisted of an office visit to determine total cholesterol, triglycerides, HDL cholesterol, fasting and two hour glucose and insulin, blood pressure, lifetime cigarette smoking, alcohol intake, reproductive history, lifetime medication usage, family history of PCOS, and serum hormone concentrations. At this evaluation, a physician diagnosis of PCOS from history, physical exam, and hormone studies was made. In addition, information on the number of pregnancies, number of live births, menstrual history, and history of surgical or natural menopause was obtained. Women with evidence of thyroid, adrenal or pituitary disease were excluded.

The grant was renewed in 1996 to determine whether women with PCOS have evidence of an increased prevalence rate of subclinical atherosclerosis. Within the PCOS population the investigators performed five studies to further determine risk factors for subclinical atherosclerosis. First, they evaluated the relationship between PCOS and subclinical atherosclerosis as measured by carotid ultrasound. In this study, they determined whether women, thirty years of age or older with PCOS, had a higher prevalence of subclinical atherosclerosis than age-matched control women. Second, they evaluated the relationship between PCOS and subclinical vascular disease as measured by brachial artery flow mediated vasodilation. They determined whether PCOS cases had lower brachial artery flow mediated vasodilation than controls, and whether the distribution of flow mediated vasodilation was related to the extent of carotid artery wall thickness and plaque. Third, they evaluated whether subclinical atherosclerosis and vascular disease were related to the following cardiovascular risk factors within PCOS cases and controls: HDL cholesterol, LDL cholesterol, triglycerides, insulin, systolic and diastolic blood pressure and testosterone, waist-to-hip ratio and body mass index (BMI). Fourth, they assessed differences in body composition between PCOS cases and control women, including intra-abdominal fat as measured by computed tomography (CT) of the abdomen and sagittal diameter, and percent body fat as measured by dual energy x-ray absorptiometry (DEXA). They evaluated the relationship between subclinical atherosclerosis and body composition separately for cases and for controls. Previous studies had clearly shown that PCOS women were different from obese non-PCOS women. Moreover, insulin, testosterone and coronary heart disease risk factors were also correlated with these measures using paired t-tests. Multiple regression was used to test whether PCOS cases compared to controls had an increase in intra-abdominal fat which was independent of important confounders. Fifth, they compared plasma levels of selected coagulation factors including fibrinogen and factor VII to fibrinolytic factors for PCOS cases and controls.

The study was renewed in September 2000 through August 2004 to continue follow-up.

Risk of Coronary Heart Disease in Women With Polycystic Ovary Syndrome

National Heart, Lung, and Blood Institute (NHLBI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Induced Atherosclerosis in Breast Cancer Patients	NCT00388713	Abnormalities, ... Atherosclerosis Breast Cancer	carotid intima-...	18 Years - 85 Years	Hadassah Medical Organization
Radiation-associated Carotid Artery Disease in Patients With Nasopharyngeal Carcinoma	NCT03568032	Nasopharyngeal ... Carotid Artery ...	Measurement of ... Detection and m... Carotid Color F... Montreal Cognit... Medical history...	18 Years -	Fudan University
Risk of Coronary Heart Disease in Women With Polycystic Ovary Syndrome	NCT00005459	Atherosclerosis Cardiovascular ... Heart Diseases Carotid Artery ... Coronary Diseas... Polycystic Ovar...		- 100 Years	National Heart, Lung, and Blood Institute (NHLBI)
Radiation Induced Atherosclerosis in Breast Cancer Patients	NCT00388713	Abnormalities, ... Atherosclerosis Breast Cancer	carotid intima-...	18 Years - 85 Years	Hadassah Medical Organization

Spots Global Cancer Trial Database for carotid artery diseases