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

NCT ID: NCT05454553

Last Updated: 2022-11-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-27
• Study Completion Date: 2024-10-27

Brief Summary

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.

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 This result is linked to outdated 2-D treatment techniques causing massive cardiac overexposure (Clarke M et al. 2005, Cheng YJ et al. 2017).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)

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Patients with left sided breast cancer who are planned for

one of the following heart sparing techniques :

• DIBH radiotherapy
• IMRT

Group Type: EXPERIMENTAL

myocardial perfusion SPECT

Intervention Type: OTHER

For all participants, myocardial perfusion SPECT will be performed :

at 3, 6 and 12 months (post irradiation)

Interventions

myocardial perfusion SPECT

For all participants, myocardial perfusion SPECT will be performed :

at 3, 6 and 12 months (post irradiation)

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Institut de cancérologie Strasbourg Europe

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut de cancérologie Strasbourg Europe

Strasbourg, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Valérie SARTORI

Role: CONTACT

v.sartori@icans.eu

368767223 ext. 33

Manon VOEGELIN

Role: CONTACT

promotion-rc@icans.eu

368339523 ext. 33

Facility Contacts

Manon VOEGELIN

Role: primary

promotion-rc@icans.eu

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Other Identifiers

ID-RCB

Identifier Type: OTHER

Identifier Source: secondary_id

2021-012

Identifier Type: -

Identifier Source: org_study_id