Radiotherapy and Oncology 185 (2023) 109734

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Radiotherapy and Oncology

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Original Article

ESTRO-ACROP guideline: Recommendations on implementation

of breath-hold techniques in radiotherapy
Marianne Camille Aznar a,⇑, Pablo carrasco de fez b, Stefanie Corradini c, Mirjam Mast d, Helen McNair e,
Icro Meattini f,g, Gitte Persson h,i, Paul van Haaren j
a
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, United Kingdom; b Servei de Radiofísica i Radioprotecció, Hospital de la Santa Creu i
Sant Pau, Barcelona, Spain; c Department of Radiation Oncology, University Hospital, LMU Munich, Germany; d Department of Radiotherapy, Haaglanden Medical Center,
Leidschendam, The Netherlands; e Royal Marsden NHS Foundation Trust and Institute of Cancer Research, UK; f Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero
Universitaria Careggi; g Department of Clinical and Experimental Biomedical Sciences ‘‘M. Serio”, University of Florence, Florence, Italy; h Department of Oncology, Herlev-Gentofte
Hospital; i Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Denmark; j Department of Radiotherapy, Catharina Hospital, Eindhoven, The
Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: The use of breath-hold techniques in radiotherapy, such as deep-inspiration breath hold, is increasing
Received 4 May 2023 although guidelines for clinical implementation are lacking. In these recommendations, we aim to pro-
Accepted 1 June 2023 vide an overview of available technical solutions and guidance for best practice in the implementation
Available online 8 June 2023
phase. We will discuss specific challenges in different tumour sites including factors such as staff training
and patient coaching, accuracy, and reproducibility. In addition, we aim to highlight the need for further
Keywords: research in specific patient groups. This report also reviews considerations for equipment, staff training
Motion management
and patient coaching, as well as image guidance for breath-hold treatments. Dedicated sections for speci-
Deep inspiration breath hold
Interfraction uncertainties
fic indications, namely breast cancer, thoracic and abdominal tumours are also included.
ESTRO ACROP guideline Ó 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 185 (2023) 109734 This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction BH techniques have been used for at least twenty years in RT.
However, the implementation has been slow, and the recent
In radiotherapy (RT), respiratory gating by using a breath-hold POP-ART survey has revealed large variations in usage amongst
(BH) technique has the potential to mitigate interfractional and RT centres and highlights that BH is still considerably under-used
intrafractional breathing-motion and/or to reduce the dose to [2]. As a result of this slow adoption, a considerable amount of
organs-at-risk (OARs), depending on the primary disease site. This pragmatic clinical knowledge is restricted to a few centres having
approach has been applied to different anatomical regions such as treated many patients. In this guideline, we have strived to com-
the thorax, breast and abdomen. bine recommendations both from published reports and from com-
The most common approach is the deep-inspiration breath- mon empirical experience (‘‘consensus of experts”) reflecting
hold (DIBH) technique: this technique requires the patients to current clinical practice. Though we recognise there is no ‘‘one-
inhale to a specified level and hold their breath during image size fits all” solution, we offer specific examples of the implemen-
acquisition and treatment delivery. Although less commonly tation of the selected technological solutions. We also discuss the
applied than DIBH, expiration BH can be advantageous for upper selection and coaching of patients, as well as specific issues relat-
abdominal tumours. ing to different patient groups (e.g. breast, lung, abdomen) for
Available strategies differ significantly with regard to adopted BH. The nomenclature used in this document is defined in Table 1
devices, additional equipment required, intrafractional monitoring and illustrated in Fig. 1.
and patient feedback systems [1]. This consensus guideline aims to
provide a broad overview of BH techniques with regard to available
solutions and their implementation, utilization, patient compli- Equipment
ance, benefits, and challenges, in order to facilitate the clinical
implementation (or expansion) of this procedure in daily practice. When implementing a BH technique in RT, a surrogate measure
for the position of the target is needed. The most commonly used
⇑ Corresponding author at: Division of Cancer Sciences, Faculty of Biology, surrogate measures can be roughly divided into surface-based or
Medicine and Health, University of Manchester, United Kingdom. spirometry-based equipment, often combined with visual feedback
E-mail address: [email protected] (M.C. Aznar). systems to the patient. The spectrum ranges from simple in-house

https://doi.org/10.1016/j.radonc.2023.109734
0167-8140/Ó 2023 The Authors. Published by Elsevier B.V.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Implementation of breath-hold techniques

Table 1
Glossary of types of breath-hold variations and their definition (BH = breath-hold). See also a visual representation in Fig. 1.

Nomenclature Definition
Interfraction BH Variation in breath-hold between different fractions (i.e. from one day to the next).Possible causes include variation in:
variation - breathing pattern (chest vs abdominal breathing);
- internal organ movement
- patient position (filling the lungs versus arching the spine).
- - drifts of organs due to relaxation/ gravity.
Intrafraction BH Variation in breath-hold within a single fraction (i.e. from beam-on to beam-stop).Possible causes include:
variation - drift due to relaxation or gravity
- patient exhaustion
- breathing pattern (chest vs abdominal breathing);
- internal organ movement
- patient position (filling the lungs versus arching the spine).
Includes two main components: BH-to-BH variation and intra-BH variation.
 Intra-BH variation: Variation within a single breath-hold, e.g. a ‘‘deep” inspiration becoming less ‘‘deep” within seconds. The breath-hold
duration may be too long, or the patient may require direct feedback to maintain the breath-hold.
 BH-to-BH variation: Variation from one breath-hold to the next within one treatment fraction. Can be caused by fatigue, shifts in patient
position as the treatment fraction is being delivered, or drifts of organs due to relaxation/gravity.

eficial to document specifically which verbal cues to use to ensure

consistent instructions are given from each staff member and avoid
confusing the patient.
Information presented as flyers, videos or slide-presentations
may be useful material that the patient can keep and use to prac-
tice BH at home if necessary [8,9]. It has been suggested that an
effective coaching process can increase the dosimetric advantage
of DIBH [10] and decrease the time required for the CT planning
scanning appointment [9]. In addition, the radiation oncologist or
other members of the treatment team can inform the patient about
the BH procedure prior to the appointment for CT planning. It must
be noted that there might be other reasons (non-performance
related) why DIBH might not be the best choice for every patient,
such as language barriers, psychological distress, or problems
understanding and following the coaching instructions. The staff
Fig. 1. Visual representation of types of breath-hold variations and their definition should reassure the patient that free-breathing (FB) is a safe option
(BH = breath-hold). See also the glossary presented in Table 1.
for treatment as well.
It is advisable to train patients in the BH procedure before com-
designs to commercially available systems that can interlock with puted tomography (CT), to familiarise them with the equipment
treatment delivery and allow automatic gating. and to inform them how the staff will communicate during the
A detailed description of equipment examples is given in the procedure. Patients can be trained directly before the planning
supplementary section (see supplementary materials S1) and an CT, i.e. in the scanning room, or during a separate coaching session.
overview of differences between the various techniques is shown The latter may be preferable for institutions beginning a BH pro-
in Table 1. Every system has advantages and disadvantages and gramme and until the staff are familiar with the coaching
is influenced by institution-specific factors, such as compatibility procedure.
with pre-existing treatment-delivery systems, patient positioning During the coaching, staff will clarify what kind of BH is
equipment, acquisition costs or experience of neighbouring institu- expected, such as ‘‘moderately deep inspiration” vs expiration
tions. It is emphasised that most approaches, no matter how tech- BH. The crucial element is that the patient feels comfortable with
nologically advanced, use surrogates for the breathing/target the procedure, in order to minimise variations in BH during imag-
motion: as a consequence, image guidance where the localization ing and treatment. It may be necessary to define a minimum
of the target can be directly verified is a necessary companion of threshold for the duration of the BH to enable Cone Beam CT
those approaches. (CBCT) acquisition or the delivery of particular beam segments:
this is particularly essential if there is no interlock between the
BH monitoring system and the linac (i.e. if the radiation therapist
Staff training and patient coaching (RTT) needs to start and stop the beam manually). Finally, the
coaching session can be useful to prevent the patient from per-
Staff training is an essential part of achieving the maximum forming BH patterns that are unsustainable (e.g. too deep, too long)
benefit of a BH technique, regardless of the equipment. It is advis- or to identify abdominal vs chest breathing. For example, the BH is
able to have 1–2 expert users [3] to develop internal protocols and often restricted to 20–30 s, for fear that longer BH may strain the
cascade training, similar to the model used for IGRT implementa- patient and introduce additional uncertainties. This doesn’t reflect
tion [4]. The number of expert users will depend on the size of the maximum BH duration achievable by patients but is meant to
the department. Well-trained and confident staff can help patients be a pragmatic compromise (i.e. ‘‘long enough” for imaging and
relax and comply [5]. Poor communication, on the other hand, may beam delivery) and is achievable by many patients [11–13]. Simi-
result in patients not tolerating the breath-hold technique [6,7]. larly, keeping BH as natural as possible for the patient (‘‘moder-
Clear communication between staff and patient is a key compo- ately deep” rather than ‘‘as deep as possible”) may avoid the
nent with written instructions and protocols. It may even be ben- need to re-scan during the course of treatment. For example, it

2
M.C. Aznar, P. carrasco de fez, S. Corradini et al. Radiotherapy and Oncology 185 (2023) 109734

has been reported that when patients try to achieve or maintain a breathing signal. Hence, regular target and organs at risk (OAR)
BH which is ‘‘too deep”, they may arch their back to compensate position verification with x-ray based images is recommended
for an insufficient BH level [14]. ‘‘Moderately deep” can be defined [25].
as roughly 70 to 85% of the maximum BH of each individual patient If the target is well correlated to bony structures (e.g., the breast
[12 15,16]. Note that in the published literature, the terms ‘‘deep” to the sternum), the position of the tumour and the BH level may
and ‘‘moderately deep” are often used interchangeably, but rarely be verified using 2D imaging (MV or kV), necessitating only a
reflect true differences in BH level. However, in the absence of few seconds of BH per image. However, it must be noted that 2D
quantitative measures, it can be useful to ask the patient to hold imaging can underestimate set-up uncertainties since not all axes
their breath without mentioning depth (‘‘imagine you’re going of deviations can be visualized [26]. A BH CBCT can be acquired
under water for 15 sec”) to achieve a natural BH. over several short consecutive BHs while pausing the image acqui-
Most patients are able to hold their breath for 25–30 seconds: sition manually to allow the patients to catch their breath, or in a
reports suggest that > 90% of breast cancer patients can achieve single BH with a fast CBCT image acquisition. Some modern linacs
DIBH [17,18], as well as a large proportion of lung cancer patients also allow automatic gated CBCT in BH. In addition to position ver-
[19] and liver cancer patients [20]. For liver and pancreatic ification and BH level verification, BH CBCT can improve imaging
tumours, a BH of 20 seconds appears to be more stable than longer quality for mobile targets considerably compared to FB CBCTs,
BH. Lens et al. described that a longer BH of 30 seconds can lead to and may help reducing interobserver registration uncertainties
a less stable tumour position, therefore shorter BHs appear to be a [1,27,28].
better approach in radiation treatments of abdominal tumours Intrafraction uncertainties such as intra- and BH-to-BH varia-
[21]. Although adequate for some treatment sites, exhale BH tions are difficult to correct and may need to be included in the
appears to be more difficult for patients, and up to 39% of patients treatment margin. Ideally, this would be done on a patient-
can be deemed unsuitable to perform an expiration BH for various specific basis: patients with small intrafractional DIBH variations
reasons [22]. benefit most from this approach, since standard margins would
result in larger margins for these patients [29]. Visual coaching
can decrease BH-to-BH variability in breast cancer patients. How-
Image-guidance for breath-hold treatments
ever, for thoracic and abdominal tumours, especially the intra-BH
variation can be difficult to assess without extensive fluoroscopic
Pre-treatment image guidance
imaging and in some cases implantation of radiopaque markers
To maximise reproducibility and reduce the risk of introducing [30–33]. Repeated DIBH CT during planning can provide an esti-
a systematic error, all relevant imaging for treatment planning mate of the BH-to-BH variation to be incorporated into individu-
should be performed in BH, and at the same BH level as used alized margins [20,34] but the method probably underestimates
throughout the treatment course. Using the same BH equipment the full extent of intrafraction motion, particularly in the abdo-
during pre-treatment imaging (dedicated CT scanners, positron men (see section 7). Therefore, cautiousness is recommended
emission tomography (PET)/CT scanners and magnetic resonance regarding PTV margins shrinkage for thoracic and abdominal
imaging (MRI) where available) and for on-treatment imaging tumours. Continuous MV or kV imaging during DIBH treatment
minimizes the risk of systematic variations between planning with open fields or with MRI on the recently clinically available
and treatment. When introducing a BH technique, some institu- MR-linacs may help us better estimate BH-to-BH and intra-BH
tions have historically acquired a FB CT followed by a BH scan dur- variations [33,35], while appropriate patient coaching may help
ing the same planning session. Although this approach can enable minimise those variations.
institutions to evaluate the dosimetric advantage of DIBH in their
own environment during the initial implementation or ‘‘learning
curve”, this approach is not recommended for routine clinical prac- Breast cancer
tice beyond the implementation stage, given the additional radia-
tion exposure. If intravenous contrast is required, it is advisable The first large-scale application of BH techniques was in
to use the contrast during the CT scan acquisition that is used for patients undergoing RT for breast cancer [36–38]. In this patient
delineating the target volume. For patients requiring PET/CT plan- group, the purpose of performing DIBH is mainly to reduce the
ning, it is possible to acquire a single PET field of view in BH (e.g. dose to the heart (by increasing the separation from the chest wall)
over 6 BHs of 20 seconds each): the PET signal acquisition can be [39], and possibly to the lungs (by increasing the total lung vol-
paused manually to allow patients to recover between BHs. In ume) [40], which can reduce the associated risks of heart disease
2015 the first use of a modified Active Breathing Coordinator [41,42] and lung cancer [43] respectively.
(ABC) in a standard MRI was described [23]. The device was mod-
ified to be MRI safe, and proof of principle of the feasibility of ABC-
Patient selection and set-up
driven DIBH during MRI was confirmed.
Several patient- and treatment-related factors may affect who is
referred to or prioritised for DIBH, such as anatomical features or
Image guidance during treatment
target volumes (e.g. regional nodal irradiation including internal
Planning target volume (PTV) margins should account for: a) mammary nodes) or laterality (left vs. right side). Patients are usu-
frequency of image guidance, b) residual tumour motion due to ally positioned supine on a flat or wedged positioning device, with
intra-BH and BH-to-BH intrafraction variation, c) differential one or both arms above the head. Reference skin marks or tattoos
motion (e.g., between involved nodes and peripheral primary can be applied in FB to facilitate initial patient alignment and set-
tumours). up, without the need of moving the patient whilst in DIBH. The
Delivery of hypofractionated treatments acquire the patient to planning CT should be performed in DIBH and additional DIBH skin
perform multiple BH with an inherent risk of exhaustion. There- marks (non-permanent) can be added as needed. An additional FB
fore, flattening filter free (FFF) beams with high output should be scan can be acquired, to create a back-up plan and/or assess the
preferred to shorten dose delivery time. effective gain between DIBH and FB plan. However, the benefits
Interfraction BH variations may be relatively large [24], and are of the acquisition of an additional FB CT scan are limited and add
not always correlated to variations in the external surrogate an increased imaging dose. The compliance in breast cancer
3
Implementation of breath-hold techniques

patients is excellent and the DIBH plan is usually not inferior to the Thoracic tumours
FB plan [49].
The primary purpose of DIBH RT for lung cancer or lymphoma is
Treatment planning and delivery: Techniques and considerations to minimise dose to the heart and lungs. For lymphoma, this is
achieved by increasing the total lung volume, as well as the separa-
DIBH is compatible with both 3D-conformal RT (3DCRT) and tion between the heart and upper-mediastinal targets. Reduced dose
Intensity Modulated Radiation Therapy (IMRT)/Volumetric Arc Ther- to the heart can decrease the risk of late radiation-induced heart dis-
apy (VMAT) techniques [44,45] and results in considerably lower ease in younger patients with a long life expectancy (e.g., those with
doses to the heart and other cardiac substructures such as the Left mediastinal Hodgkin Lymphoma) [60]. However, it is important to
Anterior Descending coronary artery (LAD). All target volumes and note that recent data suggest that heart dose also affects survival
OARs should be contoured following guidelines (i.e. ESTRO [46]). in patients with lung cancer [61,62]. More research is needed to
The maximum available dose rate should be considered to optimise understand which pathophysiological mechanisms are involved
beam delivery time (e.g. each radiation field within a single BH). and which cardiac substructures should be spared in priority.
For treatment delivery, image verification must encompass In lung cancer, an additional mode of action may be reducing
patient position (similar to treatments in FB) and verification of the motion amplitude of very mobile targets (e.g. targets close to
the BH level. As the ribs and sternum expand with the DIBH in rela- the diaphragm). However, since DIBH will introduce uncertainties
tion to the spine, the structures used for co-registration have to be both interfraction and intrafraction, it is crucial to assess the full
carefully chosen, with likely prioritisation of the upper part of the range of these uncertainties when considering any reduction of
sternum and the ribs. As with FB treatments, fiducial markers or internal target volume (ITV)/ irradiated volume [63].
surgical clips can provide additional information. Cine MV imaging
using the treatment beam can also be used to verify BH levels,
based on commercial solutions or home-made software allowing Patient selection and set-up
automatic analysis [47]; or visual evaluation [37]. SGRT and IGRT Some lung cancer patients can hold their breath long enough
are complementary technologies [48]and IGRT, specifically 3D (around 20 seconds) to facilitate treatment delivery [6,19,64] but
position verification, should be performed to get information on there are reports of insufficient respiratory capacity and poor per-
the anatomical structures. formance status in this patient population [12]. Dosimetric benefit
of DIBH for intrathoracic tumours is harder to predict than for
Published reports on uncertainties in DIBH for breast radiotherapy breast cancer patients, and, as a result, guidelines for patient selec-
tion are less straight-forward. Clinical studies have shown dosimet-
Reproducibility of the DIBH should be within 2–5 mm, regard- ric benefits with DIBH for a majority of patients (e.g. with
less of the used technique [24,49–51]. Systematic changes in BH mediastinal lymphoma [60]) but, in selected patients, DIBH can
levels may be detected during the first three treatment fractions, have a detrimental effect. If the distance between multiple targets
for example using a non-action level approach [52]. Reports of is increased in DIBH, the resulting dose delivered to the lung may
intrafraction and intra-BH reproducibility mention that an uncer- be higher than in FB [65]. Additional advantage of DIBH is improved
tainty of circa 2 mm or less is achievable [53,54]. However, there tumour visibility [28] compared to FB, especially for small mobile
may still remain a relatively large variation in heart position during tumours that would otherwise hardly be visible on 3D imaging [66].
DIBH of up to 1 cm [55]. Variations in DIBH level may be most Due to the large anatomical variation in this patient group
important in anterior-posterior (AP) direction [56,57], may occur (range of tumour size and location), it is more challenging to rec-
more frequently between fractions rather than intrafraction [24], ommend general selection criteria for DIBH. In particular, it is
and may increase with an increasing number of DIBHs per fraction important to distinguish between ‘‘simple targets” (where the
[56]. Additional verifications of BH level can include: a) the AP dis- tumour volume consists of a single solid mass), and ‘‘complex tar-
tance between the spine and sternum across the isocentre on 2D gets” with multiple target volumes (e.g. a mediastinal mass and a
set-up images, b) EPID movie loops (Figure S2), and c) 2D fluoro- peripheral lung or cardiophrenic mass).
scopic images, which are not limited to open tangential beams, With this in mind, patient selection could be based on the fol-
but cause additional dose exposure [52]. Optical surface scanners lowing criteria:
can enable a continuous real-time motion management [58] of
the patient surface during the whole fraction [48]. a) Patients with highly mobile thoracic tumours [67,68], where
In conclusion, DIBH in breast RT does not necessarily increase DIBH or other motion management approaches (abdominal
treatment precision, as new sources of uncertainties are intro- compression, expiration BH or gating) may offer margin
duced. Nevertheless, the dosimetric benefits are considerable for reduction benefits as long as DIBH-specific uncertainties
the majority of patients, especially patients with left-sided breast are also accounted for.
cancer. DIBH treatment may require an additional treatment time b) Patients with mediastinal targets where DIBH may enable
of 2–5 minutes, depending on the equipment used [59]. In the dose reduction to the heart and lungs. Note that for large
HeartSpare study, Bartlett et al. [49] found that a voluntary BH mediastinal targets extending below the heart, the dosimet-
technique (‘‘equipment free”, see S1) was associated with shorter ric benefit of DIBH may be reduced [69].
CT planning times and shorter treatment set-up times than a
spirometry-based approach (ABC, see S1). These results were Other scenarios where DIBH may be considered are dose escala-
observed despite the personnel having more experience with the tion strategies or difficulty in adhering to lung dose constraints
spirometry-based approach, and positioning reproducibility was even if the target motion is less than 5 mm (e.g. large tumours with
higher with the voluntary BH approach. little motion, where DIBH can increase the total lung volume and
Take Home message: facilitate sparing of healthy lung tissue) [70,71].

- Patient coaching is important to ensure compliance.

- Few studies compare several DIBH approaches. Treatment planning and delivery
- Voluntary approaches (using little or no equipment) have Since the dosimetric benefit of DIBH in thoracic tumours is
shown to be suitable for 3D-CRT breast treatments. more difficult to predict than in breast cancer, it is harder to make
4
M.C. Aznar, P. carrasco de fez, S. Corradini et al. Radiotherapy and Oncology 185 (2023) 109734

general recommendations for patient selection. As a result, it is Take home messages:

recommended to acquire both a FB (3D or 4D) CT scan and a DIBH
CT scan for radiotherapy planning. Note that in some complex tar- - DIBH has shown promising results in thoracic tumours but fur-
gets, DIBH may actually increase dose to the healthy lung [65]. The ther research is needed to clarify which patients get the most
heart, and possibly cardiac sub-structures, should be contoured benefit.
according to guidelines to estimate dosimetric benefit [72,73]. - Margin reduction should be approached with caution, and with
Online CBCT-based IGRT is necessary when using BH for tho- consideration of all uncertainties introduced by the DIBH proce-
racic tumours, since all surrogates, whether surface-based or dure itself.
volume-based, can be poorly correlated with the actual position - However, DIBH may offer a dosimetric advantage in some
of the tumour. Post-treatment or in-treatment imaging reflecting patients even without margin reduction, due to the modifica-
the position of the tumour is particularly desirable in this anatomic tion of the internal anatomy (lung inflation and increased sep-
district in order to estimate intrafraction motion. aration between the heart and the target volume(s)) and
reduced displacement of the tumour.
- Pragmatic intrafraction monitoring strategies where the target
Published reports on uncertainties in DIBH for thoracic tumours
position BH-to-BH and intra-BH can be verified during the
DIBH in patients with complex tumours (i.e. multiple target vol- treatment (preferably without interrupting it) are sorely
umes) is particularly challenging: lack of interfraction repro- needed. In the meantime, those variations may be estimated
ducibility in BH level may affect the distance between target using pre- and post-treatment images.
volumes and is difficult to correct in the absence of online adaptive
solutions. BH for small lung tumours treated with stereotactic body
Abdominal tumours
RT (SBRT) is a simpler case with the main purpose of motion man-
agement and/or better target visualisation.
The abdomen is arguably one of the most challenging anatom-
In a locally advanced NSCLC cohort, interfraction-BH tumour
ical site for motion management. Abdominal organs are affected by
position variations > 1 cm in all directions were detected during
respiration, and motion of up to 40 mm has been reported, mostly
the 6-week course of RT using a spirometry-based technique,
in the superior-inferior direction [77,78]. In addition, interfraction
despite little variation in lung volume and little BH-to-BH variation
motion and deformation are also present as a result of peristalsis
on CT in the planning session [74]: the authors conclude that
and digestive processes. By reducing respiratory motion, BH has
breath-hold patterns can change during treatment, and highlight
the potential to reduce the irradiated volume and improve the
the role of 3D image guidance.
quality of 3D images.
It is important to remember that surrogate signals can be poorly
For tumours of the liver and pancreas, hypofractionated regi-
correlated with the true position of the internal targets. In this sce-
mens [79–81] are being investigated to improve local control
nario, during-treatment and/or post-treatment imaging may be
[80] and motion management, such as BH, may help deliver these
necessary to estimate intrafraction motion. Few studies have
high doses while sparing the critical structures (bowel, stomach
investigated BH-to-BH variations, and even fewer investigate
and duodenum). It is important to note, however, that anatomical
intra-BH variations. This may be due to the complexity of acquiring
variations in the abdomen are both larger and less predictable than
reliable (e.g. 3D) images during treatment, concerns about patient
in the thorax, and motion related to digestive processes and
fatigue (since post-treatment imaging requires additional BHs) or
abdominal gas cannot be addressed by BH alone. The following
additional dose (especially in younger patient groups, such as
sections will focus on tumours of the liver and pancreas, as the role
Hodgkin Lymphoma (HL)).
of BH in adrenal gland and kidney SBRT is more uncertain and fur-
A study analysed fluoroscopic movies acquired during DIBH and
ther research is needed [27].
FB of nine patients with locally advanced NSCLC reported average
(maximum) intra-BH variations of 1.4 (3.4), 1.2 (4.8), and 2.1 (5.1)
mm in the AP, LR, and CC directions and a maximum BH-to-BH
Patient selection and set-up
variation of 4.5 mm in the CC direction for visually guided DIBH
[32]. For lung SBRT, two studies, both using surface guidance with For abdominal sites, BH is mostly used as motion management
visual feedback in patients with highly mobile tumours (>1 cm), strategy. As a result, a deep inspiration is not the primary goal and
have contradictory results. Peng et al. found that margin reduction some authors suggest that an expiration BH is more reproducible
was possible due to GTV position reproducibility within 1.5 mm [7,34,82]. A possible disadvantage is the lower compliance in expi-
(intra-BH and BH-to-BH) for voluntary inspiration BH with CBCT- ration BH: in hypo-fractionated liver treatment, a range of compli-
guidance based on multiple planning BH-CTs of 13 patients [75]. ance rates have been reported (61% in expiration BH [22] compared
In contrast, Ottosson et al. found that a margin expansion of to 95% [20] in inspiration BH), though it must be noted that com-
3.5 mm in the CC-direction was needed to encompass an increased paring compliance between studies is challenging. In healthy vol-
intrafraction variation based on analysis of pre- and mid-fraction unteers asked to hold their breath for up to 60 s, it has been
CBCTs of 42 patients [63]. suggested that intra-BH motion of the pancreas was noticeably
Several studies report BH-to-BH variation at the time of CT reduced in expiration BH [83]. Few recommendations have been
planning, by acquiring multiple CTs in subsequent BHs, as a mea- published about patient selection. Huang at al. [84]suggest that
sure of overall BH-to-BH variation [11,74]. However, in a cohort patients with a larger body habitus have a higher inflation of lungs
of patients with complex targets from HL, sarcoma and lung can- in DIBH (measured by spirometry) and higher positional errors in
cer, the initial measured inter-DIBH variation underestimates the the SI directions. Abdominal SBRT is performed in supine position,
variation measured during the treatment course [11,75,76]. and reference skin marks or tattoos can be applied in FB.
It should be noted that there is little information on intrafrac- Patient selection is similar to that for thoracic tumours and
tion variation for thoracic tumours treated in FB, and it is hard to mainly includes the following criteria: Patients with very mobile
distinguish between variations due to (DI)BH and variations tumours (>5mm), in whom BH or other motion management
caused by other phenomena (e.g. changes in breathing patterns, approaches (abdominal compression, expiration BH or gating)
patient position, anatomical changes) also occurring in FB may offer advantages in reducing irradiated volume compared to
treatments. FB approaches.
5
Implementation of breath-hold techniques

Treatment planning and delivery uncertainties, while the on-board continuous imaging can assess
residual BH-to-BH and intra-BH motion [93–95].
As mentioned above, anatomical variations in the abdomen are
Take home messages:
a combination of several physiological processes, including respi-
ration and digestion. To address this complex situation, multiple
- Anatomical variations in the abdomen occur frequently, and are
BH CT scans can be made for target delineation, and the informa-
arguably the most complex to characterise compared to other
tion used to calculate patient-specific margins [20,85]. Though
treatment sites.
these additional planning scans may provide information about
- Repeat BH CTs at the time of planning do not capture the full
residual intrafraction motion (BH-to-BH and intra-BH variation),
extent of intra-BH and BH-to-BH variations but may give infor-
the full extent of on-treatment motion may not be reflected [86].
mation about the BH-to-BH variation for the individual patient
BH fluoroscopy performed as part of the planning session can also
(to be included in the CTV-PTV margin [20].
help estimate intrafraction motion [82]. The use of population-
- Additional imaging (e.g. repeat fluoroscopy [7]) or screening
based CTV-PTV margins of 5 mm was suggested [87] but an indi-
may be required to identify patients with stable anatomy under
vidualised margin approach may be more appropriate if all
BH.
involved uncertainties can be quantified [20,27,85].
Online position verification is mandatory and registration using
bony anatomy is not recommended due to the substantial internal
Discussion
anatomical changes and deformations in this region [88,89]. Surro-
gate structures can be delineated during treatment planning in
This consensus guideline gives a broad overview of the available
order to help with image guidance, e.g., the diaphragm-liver inter-
technical solutions (see suppl. Section) and reports of their clinical
face, the liver volume, and natural, iatrogenic or implanted fidu-
implementation to date.
cials [79,88] for liver tumours. If fiducials are not present, the
In view of the available evidence, and the limited number of
diaphragm dome is often the surrogate structure of choice for liver
studies evaluating the impact of DIBH implementation and work-
tumours, but is not considered an appropriate surrogate for pan-
flow, we recommend that the ‘‘ideal” implementation would
creatic tumours [21].
include:
During treatment delivery, 2D imaging can be complemented
with fluoroscopy to assess intra-BH variations. For SBRT treat-
1) A lead professional or multi-disciplinary team to oversee the
ments a BH CBCT is recommended to assess liver deformation
process and be responsible for the implementation process,
and monitor the position of critical OARs where sparing needs to
specifically staff training and verification of the BH.
be prioritised even at the expense of PTV coverage (e.g. duodenum,
2) Adequate and appropriate time for staff training and patient
stomach and colon) [90,91].
coaching. The procedure can be streamlined later, but the
Overlaying isodoses critical for OARs onto the CBCT [82] may be
implementation requires more time.
helpful. All actions prior to treatment should be as fast as possible
3) The chosen system to be available on all scanners used for RT
to avoid patient motion (e.g a fast CBCT protocol [1]). If consider-
planning (CT, PET-CT, MRI) to ensure consistency of all
able changes in BH trace or a drift (larger than the expected BH-
images used for treatment planning, as well as (at least)
to-BH variation) are observed during treatment, imaging should
two treatment machines (linacs, ideally mirrored).
be repeated, and repositioning should be considered. If there is a
4) Daily imaging for the verification of the position of the target
systematic variation for two consecutive fractions in a SBRT treat-
in BH as well as verification of the BH level (if necessary to
ment, replanning should be considered depending on the clinical
ensure consistency in OAR sparing).
effects of this systematic variation [92], e.g. if it results in an
5) Target-related intra-fraction (intra-BH and BH-to-BH) moni-
acceptable dose to critical OARs. This needs to be decided on a
toring (rarely available at the moment)
patient-by-patient basis.
6) Ability to re-image and re-plan the patient if any change of
breathing pattern is suspected
7) Time and resources for each institution to carry its own
quality assurance programme to assess interfraction and
Published reports on uncertainties in BH for abdominal radiotherapy
(ideally) intrafraction uncertainties [96].
Compared to other tumour sites, there is a large body of
research on intrafractional uncertainties in abdominal tumours. The last point should not be underestimated: BH is a valuable
Reported intrafractional uncertainties have included BH-to-BH dis- tool, but its success may vary according to implementation proce-
placements of the tumour of > 3 mm [29], intra-BH displacements dures and patient population. As a result, each system might lead
of up to 1 cm [86]and ‘‘slow drifts” during BH [83]. Importantly, to different results in different institutions. Since ‘‘ideal” situations
these variations are not always detected by pre- and post- are rarely realistic in the real world, we would encourage users to
treatment CBCT evaluation, nor by repeated BH CTs. In contrast, consider aligning the reproducibility and accuracy of the BH proce-
in a study where patients were pre-selected before liver SBRT, dure with the complexity of their planning, delivery and image
excellent intra-BH stability (<2mm in SI direction) was observed guidance approach. The reproducibility and accuracy required
during expiration BH throughout the treatment course [7]. In this from a BH strategy will be different for a tangential breast treat-
study, patients were screened before treatment using repeat fluo- ment with open-beams (a treatment strategy more ‘‘forgiving” of
roscopies, and patients with a residual intra-BH motion uncertainties) than for a VMAT SBRT liver treatment.
of > 5 mm were deemed unsuitable for treatment in BH [7]. Ultra- In this guideline we focused on the main applications of BH and
sound imaging [31] may offer an alternative and non-ionising did not describe the use of a BH technique in children, as sparse
method of monitoring intra-BH stability. data are published concerning this population. Two studies
Motion management in the treatment of abdominal tumours, reported that the dose to the organs at risk could be diminished
especially with SBRT, is an active field of research. Recent reports using a BH technique [49,53]. The ‘‘TEDDI” trial (NCT03315546)
of MR-guided RT are offering a unique insight into geometric will investigate the dosimetric benefits as well as reproducibility
uncertainties in liver and pancreatic treatments. The online adap- and compliance/psychological impact of using breath-hold in pae-
tive pathways available on MR-linacs can address interfraction diatric patients [97].
6
M.C. Aznar, P. carrasco de fez, S. Corradini et al. Radiotherapy and Oncology 185 (2023) 109734

Another limitation of this guideline is that we only considered Acknowledgments

widely available approaches. Recent reports have investigated
the feasibility of longer breath-holds with ventilator-assisted solu- The authors would like to thank Dr Anna Kirby, Prof Stine Kor-
tion [98]. Though the early results are promising, more results are reman, Dr Robin Garcia, Dr Rianne de Jong and Dr Sofia Rivera for
needed about the tolerability and pragmatic implementation of their comprehensive review of this guideline. In addition, we
these approaches. Newer technology, such as MR-guided linacs, would like to thank Dr Livia Marrazzo (Azienda Ospedaliero-
may address some of the limitations listed in the guideline: MRI- Universitaria Careggi, Florence, Italy) and Dr Ko van Wingerden
guided BH or gating approaches with a direct visualisation of soft (Haaglanden Medical Center, Leidschendam, The Netherlands) for
tissue are feasible and overcome the necessity of invasive fiducials providing illustrations for the figures.
implantation [99,100]. Finally, we tried to highlight where more
research was needed (e.g. intrafraction monitoring) and where Appendix A. Supplementary material
caution should be advised for a safe implementation of BH.
In conclusion a BH technique can contribute to a more targeted Supplementary data to this article can be found online at
treatment delivery and/or allow better sparing of surrounding https://doi.org/10.1016/j.radonc.2023.109734.
organs at risk. Every institution should find the most effective
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