Deep Inspiration Breath-Hold in the prevention of radiotherapy-induced cardiac injury

Deep Inspiration Breath-Hold para a prevenção da lesão cardíaca induzida por radioterapia

Abstract

Introduction  Breast-conserving surgery followed by adjuvant radiotherapy remains the gold standard in early-stage breast cancer treatment. However, incidental cardiac irradiation increases the risk of ischemic heart disease, the leading nonmalignant cause of death among these patients.

Objective  To identify evidence-based implications of the Deep Inspiration Breath-Hold (DIBH) technique for preventing cardiac injury associated with adjuvant radiotherapy.

Methods  A scoping review was conducted in accordance with Joanna Briggs Institute guidelines. The PubMed, LILACS and Web of Science databases were searched for studies reporting the application of DIBH within the context defined by this review.

Results  Fifteen relevant studies were selected, all assessing DIBH for the prevention of cardiotoxicity secondary to adjuvant radiotherapy. Deep inspiration increases lung volume, expanding the thoracic cavity and displacing the heart to the right and downward, thereby moving the heart out of the radiation field and reducing cardiac exposure.

Conclusion  The results presented across multiple studies indicate that the use of DIBH in clinical practice consistently reduced cardiac irradiation without compromising target coverage.

Keywords:
Breast neoplasms; Adjuvant radiotherapy; Cardiac diseases; Cardiotoxicity; Breath-hold technique

Resumo

Introdução  A cirurgia conservadora da mama seguida de radioterapia adjuvante consiste no padrão-ouro de tratamento dos estágios iniciais do câncer de mama. No entanto, a irradiação cardíaca incidental aumenta o risco de doença cardíaca isquêmica, o que representa a principal causa de morte não maligna nestas pacientes.

Objetivo  Identificar as implicações, suportadas por evidências, da utilização da técnica Deep Inspiration Breath-Hold (DIBH) na prevenção da lesão cardíaca induzida por radioterapia adjuvante.

Métodos  Trata-se de uma revisão de escopo baseada nas recomendações do Joanna Briggs Institute. Foram selecionados artigos publicados nas bases PubMed, LILACS e W, que relataram a prática de DIBH, conforme o escopo do presente estudo.

Resultados  Foram incluídos quinze estudos relevantes que relataram a utilização de DIBH para a prevenção de cardiotoxicidade secundária à radioterapia adjuvante. Durante a inspiração profunda, a cavidade torácica se expande em função do aumento do volume pulmonar, deslocando o coração para a direita e inferiormente, minimizando o campo de tratamento e afastando o coração do campo de irradiação.

Conclusão  Os resultados cumulativos de uma série de estudos apontam que na prática clínica a utilização de DIBH resulta em menor irradiação do coração, sem comprometer a cobertura do alvo.

Palavras-chave:
Neoplasias de mama; Radioterapia adjuvante; Cardiopatias; Cardiotoxicidade; Suspensão da respiração

Introduction

Breast cancer is the most commonly diagnosed cancer in women worldwide. Globally, there were 2.3 million new cases and 670,000 deaths from female breast cancer in 2022 alone.¹ The majority of cases occur in transitioning countries, where mortality rates are disproportionately higher in women over 50 years old when compared to those in high-income nations.²

Key risk factors include genetic predisposition, estrogen exposure (both endogenous and exogenous, including long-term hormone replacement therapy), ionizing radiation, low parity, high breast density, and a history of atypical hyperplasia. A Western-style diet, obesity, and alcohol consumption also contribute to increased incidence.³,⁴

Modern breast cancer treatment is multimodal and combines early detection with locoregional therapies (breast-conserving surgery and radiotherapy), systemic treatments (chemotherapy, hormone therapy), and supportive care. Consequently, patients with breast cancer represent a major survivor population within oncology.⁵,⁶ Treatment selection depends on tumor stage and size, lymph node involvement, molecular subtype, patient clinical status, and other factors.⁷,⁸

Breast conserving surgery (BCS) followed by whole-breast radiotherapy is considered the gold standard treatment in early-stage disease, defined as invasive carcinoma confined to the breast, with or without regional lymph node involvement, and amenable to surgical excision.⁸ BCS involves removing the tumor while preserving the breast.⁹,¹⁰More than 80% of patients with breast cancer undergo primary surgery.¹¹

To reduce recurrence risk and improve survival out-comes, adjuvant locoregional thoracic radiotherapy is standard after BCS.¹² Combining radiotherapy with surgery is an independent prognostic factor for both breast cancer-specific and overall survival, and for reducing the risk of locoregional recurrence.¹³-¹⁵

Despite its therapeutic benefits in breast cancer treatment, radiotherapy exposes healthy tissues to ionizing radiation, in addition to targeting cancer cells.¹⁶Scatter to adjacent normal tissues is unavoidable, potentially compromising cosmetic results and inducing cardiac and pulmonary toxicity.¹⁷,¹⁸

A major adverse effect of radiotherapy is incidental cardiac radiation, which increases the risk of therapy-related cardiovascular mobility and remains the leading non-malignant cause of death in oncology patients.¹⁹-²¹Cardiotoxic manifestations include cardiomyopathy, cardiac fibrosis, coronary artery disease, arrhythmias, and hypertension.²² Thus, the therapeutic benefits of radiotherapy may be partially offset by adverse cardiovascular outcomes.²³

Given improvements in long-term breast cancer survival rates, preventing or managing radiation-induced cardiovascular diseases has become a critical challenge in clinical practice, since these late complications can adversely affect patient outcomes, quality of life, and healthcare costs. Accordingly, various preventive strategies have been proposed and implemented, focusing on reducing cardiac exposure to radiation. Against this backdrop, the present study aimed to identify evidence-based implications of the Deep Inspiration Breath-Hold (DIBH) technique for preventing cardiac injury associated with adjuvant radiotherapy.

Methods

This scoping review was conducted in accordance with the Joanna Briggs Institute guidelines (JBI Manual for Evidence Synthesis: Chapter 11: Scoping Reviews).²⁴Scoping reviews are designed to address broad research questions, provide comprehensive and in-depth analyses of existing studies, evaluate emerging evidence, and offer a solid foundation for future research. They also enable the systematic identification, examination, and organization of concepts or characteristics within a wide field of knowledge.

The methodology comprises five stages: 1) developing the research question; 2) identifying relevant studies; 3) study selection; 4) data charting; and 5) collecting, summarizing, and reporting results.

The review was guided by the following research question: What is the current evidence regarding the benefits of the DIBH technique in preventing radio-therapy-induced cardiac injury in women with breast cancer?

A systematic search was performed in PubMed/MEDLINE (National Library of Medicine); LILACS (Latin-American and Caribbean Health Sciences Literature) and Web of Science (Clarivate Analytics). A manual search of the grey literature was also conducted using Google Scholar, the U.S. National Library of Medicine, OpenGrey, and Grey Literature Report.

The search strategy combined the following descriptors: (“Deep Inspiration Breath-Hold" OR DIBH) AND ("Breast Cancer" OR " Breast Neoplasms") AND ("Radiation-Induced Heart Disease" OR “Radiation-induced Cardiovascular Disease” OR “Radiation-Associated Cardiovascular Dysfunction”).

Inclusion criteria were full-text articles published in Portuguese, Spanish, or English, between 2019 and 2024, reporting the use of DIBH in women diagnosed with breast cancer (right or left) undergoing adjuvant therapy.

To prioritize studies according to evidence quality, the categorization proposed by Fineout-Overholt et al.²⁵ was applied: 1 – systematic reviews, meta-analyses, or clinical guidelines based on systematic reviews of randomized controlled trials; 2 – randomized controlled trials; 3 – well-designed clinical trials without randomization (quasi-experimental); 4 – cohort and/or case-control studies; 5 – systematic reviews of qualitative studies; 6 – evidence from a single descriptive or qualitative study; 7 – expert opinion or committee consensus.²⁵

All retrieved studies were independently screened for eligibility by two reviewers, in two stages: (i) assessment of titles and abstracts; (ii) full-text review of the selected studies, with exclusion reasons documented. For each included study, both reviewers extracted qualitative information (authors, year of publication, journal) and clinical data (study characteristics, main outcomes, and reported adverse effects). Extracted data were organized and synthesized narratively.

Results and discussion

The search strategy identified 97 relevant studies, of which 15 met the inclusion criteria and were incorporated into the qualitative synthesis (Figure 1). A summary of the qualitative findings is presented in Tables 1 and 2.

Figure 1
Flow diagram depicting the identification, screening, exclusion and inclusion of studies.

This review highlights several key findings: (I) DIBH reduces radiation exposure to organs at risk (OAR) in patients with both left- and right-sided breast cancer; (II) it achieves significant dosimetric reductions (Gy) compared with free breathing (FB); (III) target coverage remains uncompromised; (IV) benefits are more pronounced in selected patients; and (V) preparatory physical conditioning can further enhance outcomes.

Breast radiotherapy, particularly for left-sided disease, is associated with an increased risk of long-term cardiac comorbidities.²⁶,²⁷ Exposure of a significant volume of the heart to high-dose irradiation can damage nearly all its structural components, including the pericardium, myocardium, valves, coronary arteries, capillaries, and conduction system. The latency of these effects ranges from months, in the case of subclinical changes such as pericarditis, to decades, as in the development of coronary artery disease or myocardial infarction.²⁸,²⁹

Evidence from observational studies indicates that the radiation dose, volume of the irradiated myocardium, and delivery technique influence the likelihood and severity of cardiac toxicity. Among these, the volume of irradiated heart tissue is a major determinant.³⁰Importantly, the risk of ischemic heart disease increases proportionally with the mean heart dose.²⁹,³¹

Table 1
Narrative synthesis summarizing general characteristics of the studies

Author/Country/Year	Title	Method	Evidence quality
Wolf et al.56 Germany, 2023	Deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a single-institution retrospective dosimetric analysis of organs at risk doses	Case series	4
Borgonovo et al.57 Switzerland, 2022	Deep inspiration breath hold in post-operative radiotherapy for right breast cancer: a retrospective analysis	Case report	4
Stowe et al.58 United States, 2022	Heart sparing radiotherapy techniques in breast cancer: a focus on deep inspiration breath hold	Literature review	6
Falco et al.59 Poland, 2021	Deep inspiration breath hold reduces the mean heart dose in left breast cancer radiotherapy	Case series	4
Kalet et al.60 United States, 2021	The dosimetric benefit of in-advance respiratory training for deep inspiration breath holding is realized during daily treatment in left breast radiotherapy: A comparative retrospective study of serial surface motion tracking	Case series	4
Ferdinand et al.61 India, 2021	Dosimetric analysis of Deep Inspiratory Breath-hold technique (DIBH) in left-sided breast cancer radiotherapy and evaluation of pre-treatment predictors of cardiac doses for guiding patient selection for DIBH	Case series	4
Author/Country/Year	Title	Method	Evidence quality
Reitz et al.62 Germany, 2020	Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer	Case series	4
Simonetto et al.63 Germany, 2019	Does deep inspiration breath-hold prolong life? Individual risk estimates of ischaemic heart disease after breast cancer radiotherapy. (SAVE-HEART)	Clinical trial	2
Testolin et al.64 Italy, 2019	Deep inspiration breath-hold intensity modulated radiation therapy in a large clinical series of 239 left-sided breast cancer patients: a dosimetric analysis of organs at risk doses and clinical feasibility from a single center experience	Retrospective study (Case series)	4
Schröder et al.65 Germany, 2021	Deep inspiration breath-hold for patients with left-sided breast cancer - A one-fits-all approach? A prospective analysis of patient selection using dosimetrical and practical aspects	Case series	4
Zhu et al.66 China, 2023	Cardiac exposure in left-sided breast cancer patients undergoing deep inspiratory breath hold radiation therapy	Case series	4
Swathi et al.67 India, 2024	How effective is deep inspiration breath hold in minimizing cardiac doses during hybrid radiotherapy treatment for left-sided breast cancer with comprehensive regional nodes?	Case series	4
Knöchelmann et al.68 Germany, 2022	Left-sided breast cancer irradiation with deep inspiration breath-hold: changes in heart and lung dose in two periods	Case series	4
Melo69 Brazil, 2023	Análise comparativa das doses cardíacas recebidas por pacientes com câncer de mama esquerda planejadas com duas formas alternativas de delineamento do CTV da cadeia mamária interna	Case series	4
Leoni et al.70 Brazil, 2024	Impacto da técnica de retenção do fôlego na dose cardíaca e pulmonar em pacientes submetidos à radioterapia da mama esquerda	Case series	4

Table 2
Narrative synthesis summarizing the main clinical outcomes

Author/Year	Key findings
Wolf et al. (2023)56	In a cohort of 130 patients receiving adjuvant RT with DIBH, the mean heart dose (Dmean) was 1.3 Gy (0.5–3.6) with DIBH versus 2.2 Gy (0.9–8.8) with FB (p < 0.001). For the left ventricle, Dmean was 1.5 Gy (0.6–4.5) with DIBH versus 2.8 Gy (1.1–9.5) with FB (p < 0.001). All the dosimetric parameters evaluated showed statistically significant dose reductions with DIBH (p < 0.01).
Borgonovo et al. (2022)57	In 10 patients with right-sided breast cancer, DIBH yielded a mean heart dose of 1.76 Gy versus 2.19 Gy with FB, reducing the radiation dose to the heart, LAD, and liver (in hepatomegaly cases). When correctly applied, patients tolerated the technique well, supporting its effectiveness even in right-sided breast cancer.
Stowe et al. (2022)58	DIBH offers a straightforward, non-invasive means of reducing radiation-induced cardiac toxicity in adjuvant breast RT, but not all patients tolerate it or benefit dosimetrically. Implementation should be individualized according to patient tolerance, cost, convenience, and the potential benefit of pre-RT breathing training.
Falco et al. (2021)59	DIBH significantly lowered MHD compared with non-gated FB (2.1 vs. 3.48 Gy, p < 0.0001) and gated FB (3.28 Gy, p < 0.0001). DIBH reduces the mean heart dose when compared to FB techniques (gated or ungated). High-MHD cases (> 4 Gy) declined from 40% in 2014 to 7.9% in 2017, whereas DIBH adoption increased.
Kalet et al. (2021)60	Pre-treatment breathing training sustained prolonged DIBH and heart dose reductions throughout RT. It also reduced excessive chest wall excursions, especially in patients with cardiopulmonary disease.
Ferdinand et al. (2021)61	In 31 patients with left-sided breast cancer, when compared with FB, DIBH lowered mean heart dose by 39.15% (2.4 Gy vs. 4.01 Gy, p < 0.001), maximum LAD dose by 19%, and ipsilateral mean lung dose by 9.9% (p = 0.036). DIBH significantly reduces radiations doses to OAR and is recommended for all left-sided cases.
Reitz et al. (2020)62	In 103 patients with left-sided breast cancer, optical surface scanning ensured stable, reproducible DIBH across and within fractions in routine clinical practice.
Author/Year	Key findings
Simonetto et al. (2019)63	In 89 patients with left-sided breast cancer, DIBH reduced the mean heart dose by 35% (IQR: 23-46%) when compared with FB. DIBH should be offered to all patients with left-sided breast cancer. However, the greatest benefits are expected in those with a favorable prognosis, high mean heart dose, or high baseline ischemic heart disease risk.
Testolin et al. (2019)64	In 239 patients with left-sided breast cancer, DIBH and IMRT are feasible in daily clinical practice for a high percentage of unselected patients and achieved low OAR doses without compromising target coverage.
Schröder et al. (2021)65	In 72 patients selected via predefined criteria, DIBH reduced Dmean Heart by 2.8 Gy and Dmean LAD by 4.2 Gy. From a dosimetric perspective, DIBH is not universally effective for all patients, with the greatest benefits observed in selected patients.
Zhu et al. (2023)66	In 67 patients, DIBH reduced mean radiation doses to the heart, LAD, left ventricle (LV), and right ventricle (RV) by 30%, 38.7%, 39.3%, and 34.7%, respectively, compared with FB.
Swathi et al. (2024)67	n 15 patients, DIBH improved target coverage (p < 0.017) and significantly reduced heart and LAD Dmean values (p < 0.001) compared with FB. DIBH significantly reduced radiation doses to the heart and DA in relation to FB.
Knöchelmann et al. (2022)68	In 159 patients, DIBH significantly reduced mean heart dose from 2.64 Gy to 1.39 Gy and mean LAD dose from 5.68 Gy to 3.88 Gy (both p < 0.001).
Melo (2023)69	In 43 patients, DIBH decreased mean heart dose even in patients with extensive nodal irradiation (692 cGy vs 502 cGy - p < 0.0001) and lowered left ventricle (1222 cGy vs 857 cGy p < 0.0001) and LAD doses (3739 cGy vs 3345 cGy p = 0.0001). Simplified protocols may benefit selected patients at centers with high demand and limited resources.
Leoni et al. (2024)70	In 64 submitted to left-sided breast RT (2021 to 2023) mean heart dose decreased by 46.13% (±18.06%) and mean LAD dose by 65.86% (±22.21%).

• Note: DIBH = Deep Inspiration Breath-Hold; Dmean = mean heart dose; FB = free breathing; LAD = left anterior descending artery; MHD = maximum heart displacement; OAR = organs at risk; RT = radiotherapy.
• Note: DIBH = Deep Inspiration Breath-Hold; FB = free breathing; IMRT = intensity-modulated radiotherapy; LAD = left anterior descending artery;
• OAR = organs at risk; RT = radiotherapy.

At present, the only proven strategy to prevent radiation-induced heart disease is to reduce cardiac radiation exposure during left-sided breast radiotherapy.³²,³³ This can be achieved through dosimetric optimization methods (partial breast irradiation, intensity-modulated radiotherapy-IMRT, volumetric modulated arc therapy-VMAT) or techniques that physically displace the heart from the treatment field, such as DIBH.³⁴,³⁵,³⁶ Any measure that lowers cardiac doses is likely to reduce long-term adverse outcomes.³⁷

The introduction of evidence-based radiotherapy protocols and the routine use of respiratory control methods implemented in all modern linear accelerators have reduced treatment-related morbidity. In this context, advanced techniques, such as DIBH, have been increasingly incorporated into clinical practice to minimize the risk of cardiac comorbidities.²⁶,³⁸,³⁹

DIBH is a well-established heart-sparing approach that can be easily applied in clinical practice and combined with other interventions. By exploiting natural respiratory physiology, this non-invasive technique increases the distance between the heart and the treatment field during radiotherapy.⁴⁰ During deep inspiration, the diaphragm flattens and the lungs expand, displacing the heart away from the chest wall, reducing its exposure to radiation,⁴¹ and often leading to significant dose reductions in the left anterior descending artery (LAD). During treatment, patients inhale deeply and hold their breath for 15-30 seconds while the radiation is delivered. By using DIBH, substantial sparing of vulnerable cardiac substructures can be achieved when compared with free breathing techniques.⁴⁰-⁴²

DIBH is based on the principle that active control of breathing reduces both mean heart dose and LAD dose.⁴⁰,⁴¹ Patients at high cardiovascular risk or with favorable tumor prognosis derive the greatest benefit. The technique significantly lowers doses to OAR and is recommended for all patients receiving radiotherapy for left-sided breast cancer.⁴³ Its simplicity means that minimal equipment is needed for implementation, such as a laser-based positional guidance system, audiovisual monitoring, and a verification system for patient setup.⁴³,⁴⁴

Meta-analytic data indicate that incorporating DIBH into postoperative radiotherapy for left-sided breast cancer reduces cardiac, LAD, and left lung doses without affecting target coverage compared with control groups. There were no significant differences in target coverage between groups (SMD = 0.03, 95%CI – 0.11 ~ 0.18, p = 0.64).⁴⁵

Similar findings have been reported for right-sided breast cancer. Patients in the DIBH group received significantly lower doses to the heart, liver, and lungs than those in the FB group (heart: SMD = -0.63, 95% CI -0.85 to -0.41; liver: SMD = -1.15, 95% CI -1.91 to -0.38; lungs: SMD = -0.79, 95% CI -1.23 to -0.35; all p < 0.05).⁴⁶

Substantial reductions in heart and lung doses are observed with DIBH regardless of the radiotherapy technique used.⁴³ Compared with FB, DIBH decreases mean heart or LAD dose by over 50%,44 reducing mean heart dose from approximately 5.2 to 2.7.⁴⁷,⁴⁸

DIBH is a reproducible, stable method for left-breast irradiation that significantly lowers the risk of late cardiac toxicities.⁴⁹ It mitigates respiratory-motion effects both during imaging (enhancing planning-phase imaging) and radiotherapy sessions (reducing cardiac and pulmonary exposure).⁵⁰ Maintaining reproducibility of the DIBH amplitude is critical, since even minor deviations can substantially alter mean heart dose.⁵¹Consistent breath-hold duration and precise positioning of the left breast or chest wall are essential between and within radiotherapy to achieve the planned dose distribution.⁵²,⁵³

Although DIBH is relatively straightforward, operational challenges remain. Successful implementation requires an experienced clinical team and comprehensive quality procedures covering all stages, from CT simulation to treatment delivery, including patient training, respiratory pattern standardization, minimum breath-hold time, planning margins and setup, imaging technique and frequency, and control during DIBH.⁵⁴

Patient cooperation and adherence, while critical, remain significant challenges. Not all breast cancer patients can sustain breath-holds long enough to perform DIBH effectively. Patients unsuitable for this technique include those with impaired pulmonary function preventing adequate breath-hold, those unable to complete training during CT simulation or to consistently reproduce breath-holds during treatment, and those for whom DIBH does not provide a dosimetric advantage over free-breathing. Thus, the decision to use DBIH in breast radiotherapy should be individualized.⁵⁴

Moreover, variations in patient instruction and radio-therapy planning can influence the extent of cardiac dose reduction achieved. Further research is needed to assess long-term clinical outcomes associated with different DIBH techniques and refine treatment planning strategies for left breast radiotherapy.⁵⁵

Conclusion

Postoperative radiotherapy for breast cancer, particularly on the left side, exposes a substantial portion of the heart to high radiation doses, leading to long-term cardiovascular effects secondary to cardiotoxicity. Strategies to minimize cardiac radiation exposure are therefore critical for preventing adverse events. Evidence from multiple studies indicates that DIBH effectively reduces cardiac dose in left-sided breast cancer radio-therapy without compromising target coverage. These findings are also applicable to right-sided breast cancer and other nearby organs at risk. The technique can be readily implemented in oncology radiology departments with minimal additional cost, and patients can undergo respiratory training to maximize performance during treatment sessions.

Nonetheless, there is a continuing need for methodologically robust studies to reinforce the use of DIBH as a routine, evidence-based approach to prevent radio-therapy-induced cardiac injury in women with breast cancer.

• Data Availability Statement
  Research data is not available.

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Edited by

• Associate editor:
  Ana Paula Cunha Loureiro

Data availability

Research data is not available.

Publication Dates

• Publication in this collection
  03 Oct 2025
• Date of issue
  2025

History

• Received
  23 Feb 2025
• Reviewed
  2 July 2025
• Accepted
  25 July 2025