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

Breast Cancer Clinical Trial

— EDIPE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05454553
• Other study ID #: 2021-012
• Secondary ID: ID-RCB
• Status: Recruiting
• Phase: N/A
• Start date: October 27, 2022
• Est. completion date: October 27, 2024

Study information

• Verified date: November 2022
• Source: Institut de cancérologie Strasbourg Europe
• Contact: Valérie SARTORI
• Phone: 368767223
• Email: v.sartori[@]icans.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 This result is linked to outdated 2-D treatment techniques causing massive cardiac overexposure (Clarke M et al. 2005, Cheng YJ et al. 2017).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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: October 27, 2024
• Est. primary completion date: October 27, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Respiratory Aspiration

Intervention

Other:
• myocardial perfusion SPECT
For all participants, myocardial perfusion SPECT will be performed : at 3, 6 and 12 months (post irradiation)

Locations

Country	Name	City	State
France	Institut de cancérologie Strasbourg Europe	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
Institut de cancérologie Strasbourg Europe

Country where clinical trial is conducted

France, 

References & Publications (20)

Boda-Heggemann J, Knopf AC, Simeonova-Chergou A, Wertz H, Stieler F, Jahnke A, Jahnke L, Fleckenstein J, Vogel L, Arns A, Blessing M, Wenz F, Lohr F. Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review. Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):478-92. doi: 10.1016/j.ijrobp.2015.11.049. Epub 2015 Dec 17. Review. — View Citation

Cheng YJ, Nie XY, Ji CC, Lin XX, Liu LJ, Chen XM, Yao H, Wu SH. Long-Term Cardiovascular Risk After Radiotherapy in Women With Breast Cancer. J Am Heart Assoc. 2017 May 21;6(5). pii: e005633. doi: 10.1161/JAHA.117.005633. Review. — View Citation

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7. — View Citation

Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, Mabuchi K, Marks LB, Mettler FA, Pierce LJ, Trott KR, Yeh ET, Shore RE. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):656-65. doi: 10.1016/j.ijrobp.2009.09.064. — View Citation

Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013 Mar 14;368(11):987-98. doi: 10.1056/NEJMoa1209825. — View Citation

Eber J, Leroy-Freschini B, Antoni D, Noël G, Pflumio C. Increased cardiac uptake of ((18)F)-fluorodeoxyglucose incidentally detected on positron emission tomography after left breast irradiation: How to interpret? Cancer Radiother. 2022 Sep;26(5):724-729. doi: 10.1016/j.canrad.2021.10.010. Epub 2022 Feb 12. — View Citation

Eber J, Nannini S, Chambrelant I, Le Fèvre C, Noël G, Antoni D. [Impact of thoracic irradiation on cardiac structures]. Cancer Radiother. 2022 May;26(3):526-536. doi: 10.1016/j.canrad.2021.08.022. Epub 2021 Oct 30. Review. French. — View Citation

Eftekhari M, Anbiaei R, Zamani H, Fallahi B, Beiki D, Ameri A, Emami-Ardekani A, Fard-Esfahani A, Gholamrezanezhad A, Seid Ratki KR, Roknabadi AM. Radiation-induced myocardial perfusion abnormalities in breast cancer patients following external beam radiation therapy. Asia Ocean J Nucl Med Biol. 2015 Winter;3(1):3-9. — View Citation

Feng M, Moran JM, Koelling T, Chughtai A, Chan JL, Freedman L, Hayman JA, Jagsi R, Jolly S, Larouere J, Soriano J, Marsh R, Pierce LJ. Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys. 2011 Jan 1;79(1):10-8. doi: 10.1016/j.ijrobp.2009.10.058. Epub 2010 Apr 24. — View Citation

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Marks LB, Yu X, Prosnitz RG, Zhou SM, Hardenbergh PH, Blazing M, Hollis D, Lind P, Tisch A, Wong TZ, Borges-Neto S. The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):214-23. doi: 10.1016/j.ijrobp.2005.01.029. — View Citation

Nieder C, Schill S, Kneschaurek P, Molls M. Influence of different treatment techniques on radiation dose to the LAD coronary artery. Radiat Oncol. 2007 Jun 5;2:20. doi: 10.1186/1748-717X-2-20. — View Citation

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Sioka C, Exarchopoulos T, Tasiou I, Tzima E, Fotou N, Capizzello A, Ragos V, Tsekeris P, Fotopoulos A. Myocardial perfusion imaging with (99 m)Tc-tetrofosmin SPECT in breast cancer patients that received postoperative radiotherapy: a case-control study. Radiat Oncol. 2011 Nov 8;6:151. doi: 10.1186/1748-717X-6-151. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy	Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans	at 3 months from the end of radiotherapy
Primary	Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy	Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans	at 6 months from the end of radiotherapy
Primary	Evaluation of DIBH and IMRT efficacy in preventing perfusion defect for left-sided breast cancer after radiotherapy	Incidence of perfusion defects on follow-up myocardial perfusion SPECT scans	at 12 months from the end of radiotherapy
Secondary	Assession of wall-motion abnormalities and left ventricular ejection fraction (LVEF) decrease	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
Secondary	Assessing the relevance of mean heart dose in the prevention of Radiation-induced heart disease (RIHD) compared to cardiac substructures.	Measurement of the doses delivered to the cardiac volumes and its substructures.	up to 12 months from the end of radiotherapy
Secondary	Influence of cardiac risk factors on post-radiation myocardial perfusion.		up to 12 months from the end of radiotherapy
Secondary	Influence of anticancer therapy exposure on post-radiation myocardial perfusion	Anticancer therapy characteristics (type)	up to 12 months from the end of radiotherapy
Secondary	Influence of anticancer therapy exposure on post-radiation myocardial perfusion	Anticancer therapy characteristics (dose)	up to 12 months from the end of radiotherapy
Secondary	Influence of anticancer therapy exposure on post-radiation myocardial perfusion	Anticancer therapy characteristics (duration)	up to 12 months from the end of radiotherapy
Secondary	Impact of the location of the tumor bed boost on the cardiac dose.	Location of the tumor bed boost	up to 12 months from the end of radiotherapy
Secondary	Impact of the location of the tumor bed boost on the cardiac dose.	Cardiac dose	up to 12 months from the end of radiotherapy