The CAROLE (CArdiac Related Oncologic Late Effects) Study
Condition: Coronary Artery Disease; Cardiac Disease; Cardiac Toxicity; Radiation; Radiation Therapy; Atherosclerotic Heart Disease; Cardiotoxicity; Breast Cancer; Lung Cancer; Lymphoma; Cancer; Carcinoma, Intraductal, Noninfiltrating
MeSH terms: Carcinoma, Intraductal, Noninfiltrating; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiotoxicity
Study type: Observational

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.
    

Observational model: Case-Control
Time perspective: Prospective
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.
      
Keywords: Coronary; Coronary Disease; Coronary Arteriosclerosis; Heart Disease; Cardiotoxicity; Breast Cancer; Carcinoma; Coronary Vessels; Radiation; Radiation Therapy; Coronary Artery Disease; CAD; RT; CT; Cardiac toxicity; Cardiac calcium score; Chest RT; Lung Cancer; Lymphoma; Cardiac CT Scan; Coronary Artery; Coronary arteries; Cardiac Side Effect; Cardiac tissue; Cardiac