Efficacity of Deep Inspiration Breath Hold and Intensity-modulated Radiotherapy in Preventing PErfusion Defect for Left Sided Breast Cancer (EDIPE) (EDIPE)

November 23, 2022 updated by: Institut de cancérologie Strasbourg Europe

Breast irradiation is known to cause radiation-induced heart disease (RIHD) many years later after radiotherapy. Recent studies suggest that RIHD could be an earlier complication and that subclinical cardiac injury can be detected such as myocardial perfusion defects. Myocardial perfusion single photon emission computed tomography (SPECT) is a sensitive and specific technique able to detect perfusion abnormalities which are more frequent in left-sided breast cancer patients because of the cardiac exposure.

The most used technique for breast cancer irradiation is tangential opposed field, but this technique exposes the left anterior descending coronary artery to high dose during left breast irradiation.

There are different cardiac sparing techniques to reduce heart exposure such as:

  • Deep inspiration breath-hold (DIBH) which displaces the heart out of the radiation beam
  • Intensity-modulated radiation therapy (IMRT) which decreases heart exposure to high doses but changes the dose distribution in the heart and increases lower doses.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In breast radiotherapy, especially for left sides breast cancers, the heart is the organ-at-risk which whose dose constraints are source of controversies. Historically breast cancer radiation therapy was associated with a significantly increased cardiac mortality. Two meta-analyses founded that the cardiac mortality risk was increased by 27% to 38%. This result is linked to outdated 2-D treatment techniques causing massive cardiac overexposure (Clarke M et al. 2005, Cheng YJ et al. 2017).

Three dimensional conformational radiotherapy reduced mean heart dose but the link between heart irradiation and radiation-induced heart damages doesn't seem to have threshold therefore to RHID is still a matter of concern (Darby SC et al. 2013; Taylor C et al. 2017).

The most used technique for breast cancer irradiation is opposite tangential field radiotherapy, however, it exposes the anterior interventricular coronary artery to a high dose during left breast irradiation (Nieder C et al. 2007). Therefore, radiotherapy techniques have developed to reduce cardiac exposure such as deep inspiration breath hold (DBIH) and intensity modulated radiation therapy (IMRT).

DBIH "mechanically" moves the heart away from the radiation beam and IMRT the dose distribution in the heart and reduces its exposure to high doses (Boda-Heggemann J et al. 2016, Lauche O et al. 2016).

Nevertheless, recent studies suggest that even with this level of cardiac exposure subclinical cardiac alterations may be detected, such as myocardial perfusion deficit (Eber et al. 2022; Marks LB et al. 2005; Gyenes G et al. 1997; Sioka C et al. 2011; Seddon B et al. 2002; Eftekhari M et al. 2015).

The heart is a complex and heterogeneous organ, however it's mostly considered as an homogeneous organ-at-risk during treatment planning in daily practice. Dosimetric optimization is therefore mainly performed on the global cardiac structure and the mean cardiac dose (MHD). Dosimetric studies reported a poor correlation between MHD and mean doses to cardiac substructures questioning the relevance of the MHD as a reflection of the dose distribution to the heart (Jacob S et al. 2016).

Recent data suggested to take account of the histological diversity and the functional complexity of the cardiac substructure (Darby SC et al. 2010; Gillette EL et al. 1985; Ghita M et al. 2020; Eber J et al. 2021). This delineation is not performed in routine clinical practice due to the poorly reproducible and time-consuming manual contouring.

The development of auto-segmentation software can save time and improve the quality of the delineation process of these substructures in order to optimize dosimetry (Feng M et al. 2011; Maffei N et al. 2020).

The investigators propose a single-centre prospective study to evaluate the utility of deep inspiration breath hold using a surface monitoring technique (AlignRT, Vision RT Ltd., London, UK) and IMRT, as means to prevent the development of myocardial perfusional deficits in patients treated for left breast cancer, using stress and, if necessary, resting myocardial scintigraphy.

Before initiation of radiotherapy patients will performed a chest CT scan in the treatment position for 3D treatment planning and dose calculation; a chest CT angiography for delineation of cardiac substructures; and a myocardial perfusion SPECT imaging to provide a map of regional myocardial perfusion and determine left ventricle ejection fraction (LVEF).

Treatment phase will consist of the standard course of breast radiotherapy in our department. The main difference will be in the delineation of the organ at risk, cardiac substructures will be delineated to obtain the dosimetry During the follow up period, patient will be scheduled to undergo cardiac SPECT before and at 3-, 6-, and 12-month period post irradiation. Stress ECG-gated SPECT will be performed after infusion of 3 MBq/kg 99mTc-tetrofosmin (Myoview®, General Electrics Healthcare) at peak pharmacological stress with regadenoson, (single dosage: 400 µg; Rapiscan®, GE healthcare)

Study Type

Interventional

Enrollment (Anticipated)

58

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • France
      • Strasbourg, France
        • Recruiting
        • Institut de cancérologie Strasbourg Europe
        • Contact:
        • Principal Investigator:
          • Martin SCHMITT, MD

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patient with left sided breast cancer histologically confirmed after lumpectomy or mastectomy with/without lymph node involvement who are planned for DIBH-RT or IMRT
  • Age > 18 years
  • Karnofsky Performance Status (KPS) > 60%
  • Absence of psychiatric illness hindering follow-up
  • Patient understands French
  • Signature of informed consent
  • Patient registered with social security

Exclusion Criteria:

  • Bilateral breast cancer
  • History of thoracic irradiation
  • Pregnancy or breastfeeding
  • Any medical contraindication of cardiac SPECT or chest CT angiography.
  • Any medical contraindication of Regadenoson

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

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with left sided breast cancer who are planned for

one of the following heart sparing techniques :

  • DIBH radiotherapy
  • IMRT
Other: myocardial perfusion SPECT

For all participants, myocardial perfusion SPECT will be performed :

at 3, 6 and 12 months (post irradiation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy
Time Frame: at 3 months from the end of radiotherapy
Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans
at 3 months from the end of radiotherapy
Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy
Time Frame: at 6 months from the end of radiotherapy
Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans
at 6 months from the end of radiotherapy
Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy
Time Frame: at 12 months from the end of radiotherapy
Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans
at 12 months from the end of radiotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assession of wall-motion abnormalities and left ventricular ejection fraction (LVEF) decrease
Time Frame: up to 12 months from the end of radiotherapy
Incidence of left ventricular wall motion disorder and LVEF quantification on follow-up myocardial perfusion SPECT scans.
up to 12 months from the end of radiotherapy
Assessing the relevance of mean heart dose in the prevention of Radiation-induced heart disease (RIHD) compared to cardiac substructures.
Time Frame: up to 12 months from the end of radiotherapy
Measurement of the doses delivered to the cardiac volumes and its substructures.
up to 12 months from the end of radiotherapy
Influence of cardiac risk factors on post-radiation myocardial perfusion.
Time Frame: up to 12 months from the end of radiotherapy
up to 12 months from the end of radiotherapy
Influence of anticancer therapy exposure on post-radiation myocardial perfusion
Time Frame: up to 12 months from the end of radiotherapy
Anticancer therapy characteristics (type)
up to 12 months from the end of radiotherapy
Influence of anticancer therapy exposure on post-radiation myocardial perfusion
Time Frame: up to 12 months from the end of radiotherapy
Anticancer therapy characteristics (dose)
up to 12 months from the end of radiotherapy
Influence of anticancer therapy exposure on post-radiation myocardial perfusion
Time Frame: up to 12 months from the end of radiotherapy
Anticancer therapy characteristics (duration)
up to 12 months from the end of radiotherapy
Impact of the location of the tumor bed boost on the cardiac dose.
Time Frame: up to 12 months from the end of radiotherapy
Location of the tumor bed boost
up to 12 months from the end of radiotherapy
Impact of the location of the tumor bed boost on the cardiac dose.
Time Frame: up to 12 months from the end of radiotherapy
Cardiac dose
up to 12 months from the end of radiotherapy

Collaborators and Investigators

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

Sponsor

Institut de cancérologie Strasbourg Europe

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)

October 27, 2022

Primary Completion (Anticipated)

October 27, 2024

Study Completion (Anticipated)

October 27, 2024

Study Registration Dates

First Submitted

June 22, 2022

First Submitted That Met QC Criteria

July 7, 2022

First Posted (Actual)

July 12, 2022

Study Record Updates

Last Update Posted (Actual)

November 29, 2022

Last Update Submitted That Met QC Criteria

November 23, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-012
  • ID-RCB (Other Identifier: 2025-A02239-40)

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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