The CAROLE (CArdiac Related Oncologic Late Effects) Study

Completed

• Conditions: Cardiotoxicity; Cardiac Toxicity; Radiation Therapy; Atherosclerotic Heart Disease; Breast Cancer; Carcinoma, Intraductal, Noninfiltrating; Radiation; Lymphoma; Cardiac Disease; Coronary Artery Disease

• Registration Number: NCT03235427
• Lead Sponsor: Northwell Health

Brief Summary

CAROLE seeks to evaluate the relationship between chest Radiation Therapy and coronary artery disease.

The purpose of CAROLE is to check the heart health of women who received breast cancer treatments in the past and protect them from future heart disease.

Detailed Description

Background: Within the United States, there are an estimated 3.1 million women alive who have been diagnosed with invasive breast cancer, and approximately 56% of them have received radiation. Worldwide, there are 1.4 million diagnosed annually and, in 2012, it was the most commonly diagnosed cancer in women. As patients continue to live longer, cardiac dose-related toxicity has become an issue which impacts millions globally. Guidelines are sorely needed for this large at-risk population of women.

Purpose: Radiation therapy to the chest has known cardiac late effects including coronary artery disease, fibrosis, and valvular dysfunction. Unfortunately, there is no clear evidence on which radiation doses to cardiac structures cause these late toxicities. As a result, these effects are often under-recognized until after patients have become symptomatic. More than half of breast cancer patients are treated with radiation, and many receive incidental cardiac irradiation. Many of these women also receive systemic therapy which may pose additional cardiac risks. The investigators data will help to establish baseline rates of pre-clinical and clinical disease, which can be used to inform preventative guidelines that are critically needed in this at-risk population. Additionally, the investigators data will provide a better definition of the radiation dose-relationship associated with cardiac toxicity so that it will be possible to predict more accurately who is at elevated risk for iatrogenic cardiac disease.

Research Plan: This study will identify and evaluate 200 breast cancer patients treated at the investigators institution (\>6 years prior) who are at risk for treatment-related cardiac toxicity. All patients enrolled in the study will receive echocardiograms (echo), electrocardiograms (EKGs), and coronary calcium (CAC) CT scans in order to comprehensively evaluate for pre-clinical and clinical cardiac disease. Patients identified as having cardiac disease during testing will be offered referral to a cardiologist. Patients who received non-radiation treatments (chemotherapy, hormonal therapy, and/or surgery) will be compared to radiated patients to establish baseline rates of preclinical and clinical disease. Patients who received cardiotoxic systemic therapy (doxorubicin, trastuzumab, etc.) will also be evaluated in subgroup analysis. Among radiation patients, this study proposes a novel method of risk assessment, which is, to utilize a patient's stored treatment plan (from 2004-2011) and fuse it with patients current cardiac imaging to delineate an accurate dose relationship associated with clinical and pre-clinical disease. This is further described in the specific aims below:

Specific Aim 1: Identify baseline levels of clinical and pre-clinical disease in breast cancer patients.

Aim 1.1: Delineate the group of patients diagnosed and treated for breast cancer between 2004-2011, enroll health system patients with recent follow up (within 3 years).

Aim 1.2: Perform non-invasive cardiac testing (EKG, echo, CAC CT scans). Aim 1.3: Establish rates of pre-clinical and clinical disease based on pre-determined criteria.

Specific Aim 2: Create an accurate dosimetric assessment of dose to cardiac structures.

Aim 1.1: Among study patients who received radiation treatment for breast cancer, obtain stored planning CT simulation scans.

Aim 1.2: Upload CT simulation scans with dosimetric information and delineate cardiac structures at risk in order to ensure accurate and reproducible target delineation.

Aim 1.3: Fuse the CAC CT scan with the CT simulation scan to accurately assess for dose correlation between coronary calcium with the dose received.

Aim 1.4: Create a dose-relationship model for the heart and cardiac structures.

Specific Aim 3: Incorporate dosimetric cardiac risk information into the investigators institution's clinical practice, publish data, and establish updated cardiac guidelines for women who have received radiation for breast cancer.

The long-term goal of the project is to elucidate specific treatment and radiation dose-related risks, which will then be used to inform follow-up recommendations and guidelines. This project will impact the way investigators describe expected cardiac risk to patients, the way the investigators recommend follow up care, and potentially, the way the investigators prescribe treatment. At present, all patients receiving radiation for breast cancer are informed that there is a risk of cardiac late effects, however, no specific cardiac imaging or intervention is recommended other than routine medical follow up. There is little distinction given to the side of the cancer, a patient's individual anatomy, or the projected dose to the anterior heart and cardiac structures. This project will allow physicians to provide a more accurate risk profile regarding future risk of cardiac morbidity. If the study reveals a very high rate of pre-clinical atherosclerotic disease, it also may prompt more routine CAC CT screening.

Study Timeline

• Study First Submitted: 2017-06-06
• Study Start: 2017-06-27
• Study First Submitted QC: 2017-07-31
• Study First Posted: 2017-08-01
• Primary Completion: 2018-06-26
• Study Completion: 2018-06-26
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-20
• Last Update Posted: 2019-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 201

Inclusion Criteria

• If you are a breast cancer survivor who was diagnosed between the ages of ≥ 18-65 years (now at age 26-78).

• It has been at least 6 years since you were diagnosed.

• If you did not have a diagnosis of heart disease before* having breast cancer.

  • (*women diagnosed with heart disease after breast cancer may still be eligible)

Exclusion Criteria

• Patients who are unable to care for themselves or who are unable to come in for testing due to health conditions or incarceration will be rescheduled or removed in the case of chronic ineligibility. No vulnerable patient populations will be used in this study. Patients will be excluded if they have any pre-existing cardiac disease at the time of diagnosis of their breast cancer (2004-2011).
• Pregnant and nursing women are ineligible.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Multimodality Cardiology Assessment- EKG	1 Year	Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including EKG.; Studies will be read using a standard, evidence based, set of criterion and documented using study templates) and compared to patients who did not receive radiation to the heart.; All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.
Multimodality Cardiology Assessment- Echocardiogram with Strain	1 Year	Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including Echocardiogram with Strain.; All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.
Multimodality Cardiology Assessment- Coronary Artery Calcium (CAC) CT	1 Year	Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including Coronary Artery Calcium (CAC) CT.; All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.

Secondary Outcome Measures

Name	Time	Method
Agatston Score	1 Year	Individual cardiac structures will be accessed using Agatston score. Agatston score is calculated using a CAC CT scan to measure for the presence of coronary artery disease based on the extent of coronary artery calcification. Specifically the left main, left anterior descending, left circumflex, and right coronary arteries are all read individually and the sum of these cardiac vessels scores is read as the overall Agatston score.; Grading of coronary artery disease (based on total calcium score) measure is without units. Score categories are as follows: No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically). Higher Agatston score correlates with more coronary artery disease.; The assessment of calcium (Agatston score) on CAC CT will be compared to the dose received by the specified vessel as determined using deformable registration with prior radiation imaging (simulation CT scan).

Trial Locations

Locations (1)

Northwell Health; 🇺🇸 Lake Success, New York, United States