The CAROLE (CArdiac Related Oncologic Late Effects) Study (CAROLE)

May 20, 2019 updated by: Lucille Lee, Northwell Health

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

201

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

26 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Women aged 18-65 at the time of breast cancer diagnosis, with a minimum of 6 years since diagnosis, with no history of heart disease prior to participants breast cancer diagnosis.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Received Radiation Therapy(RT)
Patients who had received radiotherapy will be sub-stratified into those who received treatment to the left or right breast.
Did not receive Radiation Therapy (RT)
Patients who did not receive radiation treatment, but received chemotherapy, hormonal therapy, and/or surgery will be used as study controls to compare the prevalence and burden of cardiac disease as compared to radiation patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Multimodality Cardiology Assessment- EKG
Time Frame: 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.
1 Year
Multimodality Cardiology Assessment- Echocardiogram with Strain
Time Frame: 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.
1 Year
Multimodality Cardiology Assessment- Coronary Artery Calcium (CAC) CT
Time Frame: 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.
1 Year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Agatston Score
Time Frame: 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).
1 Year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Assessment of Cardiac Disease
Time Frame: 1 Year
Sub-analysis for association of specific oncologic treatment(s) with cardiac disease (as per previously described study templates) will also be performed on patients who received multimodality treatment (RT+ chemotherapy, RT + hormonal treatment, RT+ chemo and hormonal treatment, RT + individual cardio toxic chemotherapies [anthracycline, trastuzumab, etc.]) and on different surgical approaches (lumpectomy and mastectomy). Results will be reported as a single value for each arm/group.
1 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Investigators

  • Principal Investigator: Lucille Lee, MD, Northwell Health
  • Principal Investigator: Lindsay L Puckett, MD, Northwell Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2017

Primary Completion (Actual)

June 26, 2018

Study Completion (Actual)

June 26, 2018

Study Registration Dates

First Submitted

June 6, 2017

First Submitted That Met QC Criteria

July 31, 2017

First Posted (Actual)

August 1, 2017

Study Record Updates

Last Update Posted (Actual)

May 21, 2019

Last Update Submitted That Met QC Criteria

May 20, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIS-0046

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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