Acute and Long-term Cardiovascular Toxicity After Modern Radiotherapy for Breast Cancer

Acute and Long-term Cardiovascular Toxicity After Modern Radiotherapy for Breast Cancer - a Prospective Longitudinal Study

In Europe, breast cancer is by far the most common form of cancer diagnosed in women today, accounting for 29% of all cases. The 5-year survival rate is approximately 90%. Surgery is usually combined with radiotherapy (RT), anthracyclines, aromatase inhibitors and/or trastuzumab (Herceptin) which all have improved the life expectancy and survival in breast cancer patients.

Unfortunately, RT is associated with a broad spectrum of cardiovascular diseases, which includes coronary artery disease, valvular dysfunction, congestive heart failure and stroke, and is the most common non-malignancy cause of death. During the last two decades, RT regimens for breast cancer have changed and the doses of radiation to which the heart is exposed are now potentially lower due to new and improved RT techniques. However, there are no data on whether these new regimes decrease the risk of cardiovascular disease.

In this study the incidence and prevalence of cardiovascular diseases will be estimated 8 and 15 years after both conventional and laser assisted breath controlled RT, and compared with cardiovascular diseases in the general female population. A further aim is to evaluate signs and prevalence of acute cardiotoxicity from RT with the use of cardiac magnetic resonance imaging, coronary fractional flow reserve, ECG and inflammatory and cardiac biomarkers and to investigate whether these signs can predict later cardiovascular disease. The importance of traditional cardiovascular risk factors (age, hypertension, hypercholesterolemia, smoking habits and physical activity, as registered before RT) will also be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Breast Neoplasms

Detailed Description

The study is an observational study. In 2007-2012 conventional RT was part of the common treatment regime for breast cancer, but has recently been replaced by laser assisted breath controlled RT. Thus, two cohorts of breast cancer patients treated with different modes of RT will be followed for the development of cardiovascular disease for the subsequent 15 years.

• Study Type: Observational
• Enrollment (Estimated): 1600

Contacts and Locations

• Study Contact: Name: Torgeir Wethal, md phd; Email: torgeir.wethal@stolav.no
• Study Contact Backup: Name: Jo-Åsmund Lund, md phd; Email: jo-asmund.lund@stolav.no

Study Locations

• Norway
  • Trondheim, Norway
    • Recruiting
    • St Olavs University Hospital
    • Contact: Torgeir Wethal, md phd; Email: torgeir.wethal@stolav.no
  • Ålesund, Norway
    • Recruiting
    • Alesund Hospital
    • Contact: Torstein Hole, md phd; Email: torstein.hole@ntnu.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

women treated for breast cancer with radiotherapy

Description

Inclusion Criteria:

• diagnosis of breast cancer
• expected life-expectancy above 10 years

Exclusion Criteria:

• Not willing to participate

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
conventional radiotherapy; 450 breast cancer patients treated with conventional radiotherapy with or without anthracyclines and/or trastuzumab during 2007-2012
breath controlled radiotherapy; 350 breast cancer patients treated with laser assisted breath controlled radiotherapy with or without anthracyclines and/or trastuzumab during 2015-2017
controls; per participating patient 2 age-matched female controls from the HUNT-3 population (total 800)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of cardiovascular disease	compared with corresponding estimates from the female general population (HUNT-registry data, age-matched sample)	8 years
incidence of cardiovascular disease	compared with corresponding estimates from the female general population (HUNT-registry data, age-matched sample)	15 years

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Norwegian University of Science and Technology; Alesund Hospital
• Investigators: Study Chair: Jo-Åsmund Lund, md phd, St. Olavs Hospital

Publications and helpful links

General Publications

• Reidunsdatter RJ, Rannestad T, Frengen J, Frykholm G, Lundgren S. Early effects of contemporary breast radiation on health-related quality of life - predictors of radiotherapy-related fatigue. Acta Oncol. 2011 Nov;50(8):1175-82. doi: 10.3109/0284186X.2011.604345. Epub 2011 Aug 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2036

Study Registration Dates

• First Submitted: September 1, 2015
• First Submitted That Met QC Criteria: September 2, 2015
• First Posted (Estimated): September 4, 2015

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Quality of Life; Magnetic resonance imaging; Radiotherapy; Risk factors; Biological markers; Echocardiography; Tomography, X-Ray Computed; Heart
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Cardiovascular Diseases; Breast Neoplasms
• Other Study ID Numbers: 2015/583

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No