Radiation Induced Atherosclerosis in Breast Cancer Patients

Breast Cancer Clinical Trial

Official title:

Radiation Induced Atherosclerosis in Breast Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00388713
• Other study ID #: ASBCO5- HMO-CTIL
• Status: Recruiting
• Phase: N/A
• First received: October 15, 2006
• Last updated: May 15, 2007
• Start date: October 2006
• Est. completion date: January 2010

Study information

• Verified date: December 2005
• Source: Hadassah Medical Organization
• Contact: Arik Tzukert, DMD
• Phone: 00 972 2 6776095
• Email: arik[@]hadassah.org.il
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• women 18-85 Y.O.

• received or about to receive unilateral breast and supraclavicular radiation therapy

• No evidence of disease

Exclusion Criteria:

• prisoners

Study Design

Observational Model: Defined Population, Time Perspective: Longitudinal

Related Conditions & MeSH terms

• Abnormalities, Radiation-Induced
• Atherosclerosis
• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• carotid intima-media thickening ultrasound

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

References & Publications (3)

Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol. 2003 Jan;45(1):55-75. Review. — View Citation

Cheng SW, Ting AC, Lam LK, Wei WI. Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2000 Apr;126(4):517-21. — View Citation

Dorresteijn LD, Kappelle AC, Boogerd W, Klokman WJ, Balm AJ, Keus RB, van Leeuwen FE, Bartelink H. Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol. 2002 Jan 1;20(1):282-8. — View Citation