Journal of Medical Imaging and Radiation Oncology 56 (2012) 499–509

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R ADIATION O N C O L O G Y —R EVI EW AR T I CLE

Inter- and intra-fraction motion during radiation therapy to the

whole breast in the supine position: A systematic review
Andrea Michalski,1,2 John Atyeo,1 Jennifer Cox1,2 and Marianne Rinks1,2
1
Faculty of Health Science (MRS) Radiation Therapy, The University of Sydney, and 2Department of Radiation Oncology, Northern Sydney Cancer
Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia

A Michalski BAppSc(MRS)Rad.Thpy(Hons); Summary

J Atyeo PhD, MHlthScEd, BSc(Psychology), BA;
J Cox PhD, BA(Hons) ARMIT(Med Radther);
M Rinks PhD, CertRad(Ther)BEd(AdultEd).
Correspondence
Mrs Andrea Michalski, Discipline of Medical
Radiation Sciences, Faculty of Health Sciences,
Cumberland Campus C42, The University of
Sydney, PO Box 170, Lidcombe, NSW 1825,
Australia.
Email: andrea.michalski@sydney.edu.au
Conflict of interest: None.
Submitted 8 December 2011; accepted 25
April 2012.
10.1111/j.1754-9485.2012.02434.x
Inter- and intra-fraction motion during radiation therapy for breast cancer
has been a widely researched topic. Recently, however, with the emergence
of new technologies and techniques such as intensity modulated radiation
therapy (IMRT), field in field, volumetric modulated arc therapy (VMAT),
tomotherapy and partial breast irradiation (PBI), the magnitude of this move-
ment has become more important. The aim of this study is to provide a
comprehensive summary of the literature relating to the magnitude of motion
during radiation therapy for a breast cancer patient. A systematic review of
the literature was conducted using Medline, Cinhal, Embase, Scopus and Web
of Science. Studies included were limited to women having radical radiation
therapy to the whole breast in the supine position. Studies needed to report
quantitatively on the magnitude of inter- and intra-fraction motion using
electronic portal imaging, port films or kilovoltage imaging techniques. Eight-
een articles fitted the selection criteria. The averages of random and syste-
matic error for inter- and intra-fraction movement were reported using central
lung distance, central irradiated width, central beam edge to skin distance and
cranio-caudal distance measurements, or isocentric matching techniques.
Inter-fraction motion was consistently larger than intra-fraction motion but,
on average, within a 5 mm tolerance. There were, though, large maximum
inter- and intra-fraction variations observed in the measurements of indi-
vidual patients, which indicate the need for daily inter- and intra- fraction
motion management before implementing IMRT, VMAT, tomotherapy or PBI
techniques.

Key words: breast neoplasms; health care; motion; patient positioning;

quality assurance; radiotherapy.

to treat breast cancer, and involve modulation of the

Introduction
Breast cancer is the most prevalent cancer in the world
and the second most commonly diagnosed cancer. It is
also the principle cause of death from cancer among
women globally.1 Given the incidence of breast cancer,
it is imperative that the best treatment options are
available for all patients. Intensity modulated radiation
therapy (IMRT), field in field (FIF), and more recently,
volumetric modulated arc therapy (VMAT) and tomo-
therapy are new radiation therapy techniques being used
radiation therapy beam. An important consideration
before these techniques can be implemented is their
ability to create highly conformal dose distributions,
shaped around the planning target volume (PTV). Partial
breast irradiation (PBI) is another new radiation therapy
technique that localises treatment to the tumour bed
and treats only a small volume. Compared with pre-
vious tangential breast radiation therapy, inter- and
intra-fraction motion for all these new techniques will
be of greater consequence. Immobilisation to reduce

© 2012 The Authors

Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists 499
A Michalski et al.

inter- and intra-fraction motion is therefore essential to Table 1. Measurements typically taken to determine the magnitude of inter-
ensure accurate treatment localisation of the PTV. Deep and intra-fraction motion
inspiration breath hold (DIBH) and image-guided radia-
Measurement Definition
tion therapy (IGRT) are two developments that could
assist in reducing inter- and intra-fraction motion. DIBH Central lung distance The distance between the chest wall and
is being investigated to potentially reduce the effect of posterior border at the level of central axis
respiration on treatment,2,3 whereas IGRT can be used to Central beam edge to skin/ The distance from the anterior breast outline
minimise the effect of inter-fraction motion through daily central flash distance to the anterior field edge at the level of
analysis of treatment images and immediate online central axis
Cranio-caudal distance The distance from the infra-mammary fold to
correction of patient set-up error.4
the inferior field edge
Since the introduction of the electronic portal imaging
Central irradiated width The distance between the posterior field
device (EPID),5 inter- and intra-fraction motion during border and the anterior breast outline
radiation treatment for breast cancer has been a widely Central breast distance The distance between the chest wall and
discussed topic. Researchers have found relatively the anterior breast outline at the level
minor levels of inter- and intra-fraction movement,5–9 of central axis
but sample sizes have generally been very small, owing Inferior central axis The distance between the inferior breast
to the large number of images that need to be reviewed margin† outline to the inferior field border at the
for each patient. Given these small sample sizes, lacking level of central axis
statistically significant results, it is difficult to draw con-
†This parameter is not commonly measured and will therefore not be
clusions on the magnitude of inter- and intra-fraction
discussed further.
motion.
Inter-fraction motion is the motion seen between
images taken on different treatment fractions and has
such as the chest wall–lung interface and measure their
both systematic and random components. Systematic
distance to the isocentre. This method is usually under-
inter-fraction error is the average variation in treatment
taken with computer software, with the user matching
position calculated from all treatment verification images
the images and the computer calculating the difference.
across a course of radiation therapy for a particular
patient, compared with their planning reference image
(simulator image or digitally reconstructed radiograph).8
Random inter-fraction error is the variability in patient
positioning observed between daily treatment veri-
fication images. It varies each day in direction and
magnitude.8
Intra-fraction motion is the variability seen in multiple
images acquired in rapid succession during the delivery
of a radiation treatment beam. Intra-fraction error is
considered to be random, as the variations seen in mul-
tiple images acquired during one beam-on period are
typically related to factors such as patient movement CBESD
and internal organ motion during the treatment fraction. CIW
Random intra-fraction error is the variability averaged
across all the images taken on one day and compared
with the averaged error of all the fractions where images CBD
CLD
were obtained.8
An EPID is a very useful tool for measuring inter- and
intra-fraction motion in breast radiation therapy. Images
can be acquired on a daily basis, as single images or cine
images during a radiation ‘beam on’ time, using mega-
voltage (MV) radiation. These images can then be used
to measure variations from treatment to treatment
CCD ICM
(random error) or simulation to treatment (systematic
error). Electronic portal imaging (EPI) for breast patient
set-up is a commonly used imaging method.10 Measure-
ments typically taken to determine the magnitude of Fig. 1. Measurements typically taken to determine the magnitude of inter-
these errors are indicated in Table 1 and shown diagram- and intra-fraction motion: Central lung distance (CLD), central beam edge to
matically in Figure 1. Another method of measuring the skin distance (CBESD), cranio-caudal distance (CCD), central irradiated width
magnitude of motion is to use anatomical landmarks (CIW), central breast distance (CBD) and inferior central axis margin (ICM).

© 2012 The Authors

500 Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists

Optical guidance systems that employ the use of exter-
nal markers and cameras to monitor the real-time move-
ment of a patients’ external contour are in use in a small
number of departments.11–16
IGRT can be used to minimise the effect of inter-
fraction motion through daily analysis of treatment
images and immediate online correction of any patient
set-up error prior to treatment. Kilovoltage (kV) imaging
is a more recent method of imaging for verification of
the treatment position. kV imaging provides better
image quality and contrast than MV imaging while also
lowering radiation doses,17 making it the preferred
imaging method when implementing IGRT. Cone beam
computed tomography (CBCT) is another imaging tech-
nique but is unique in that it quantifies inter-fraction
motion in three dimensions (3D). CBCT can be produced
using either MV or kV radiation, although kV CBCT is
again the preferred imaging option due to the lower
doses required, allowing for more frequent imaging, and
its improved image quality. When using kV images and
CBCT, there is no verification of the boundaries of the
treatment beam, and in the case of whole breast radio-
therapy, there is no verification of the volume of lung
in the treatment field, so it can only be used for verifi-
cation of the isocentre location. However, where daily kV
imaging or CBCT are implemented with IMRT, verifica-
tion of the treatment field is no longer possible due to the
beamlet delivery of IMRT.
The implementation of IMRT, FIF, VMAT and tomo-
therapy is important as these techniques have resulted
in a reduction in morbidities as well as an improvement
in dose distributions and cosmetic outcome for all cancer
sites, including the breast.18–20 Despite these proven
benefits, radiation oncology departments across the
world are only gradually implementing IMRT, including
the FIF technique,21,22 with very little research published
on VMAT and tomotherapy for treatment of breast
cancer,23–25 despite the advantages presented for other
sites.26–33 One reason for this is that the breast is a
highly mobile structure, reducing the accuracy of modu-
lated beams, resulting in poorer dose distributions than
expected from these techniques. These inferior dose
distributions may cancel out any advantages in reducing
morbidities. A phantom study by Yu et al.34 demon-
strated that the interplay between dynamic multileaf
collimators (MLCs) and patient motion in breast radiation
treatment can produce large errors in the delivered
photon dosimetry, possibly leading to geometric misses
of the PTV. The newly developing technique of PBI has a
target volume closely related to the volume of the sur-
gical cavity, which is much smaller than whole breast
radiation.35 The small margins mean that even small
inter- and intra-fraction motion could result in large
changes in dose distributions.
This systematic review aims to combine studies relat-
ing to the magnitude of inter- and intra-fraction motion
to provide an overall picture of motion. This will provide
© 2012 The Authors
Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists
Motion during breast radiotherapy
radiation therapy departments with an understanding of
the magnitude of motion expected. As much of inter-
and intra-fraction motion is patient related, the ideal
study would have a large sample size, but this could
mean reviewing thousands of images. By combining
these smaller studies, we are able to represent inter-
and intra-fraction motion in a large sample, which is
more representative of the population. This will help
to define target margins and potentially assist depart-
ments in implementing new techniques for breast
cancer treatment.
Methods
Selection criteria
A methodology was developed for the inclusion and
exclusion criteria based on the Cochrane Handbook
for Systematic Reviews of Interventions.36 Inclusion cri-
teria are listed in Table 2. Studies were excluded if they
measured motion using optical guidance systems, prone
breast positioning or electron radiation, as these are less
commonly used in the treatment of breast cancer.
Search strategy
A literature search was conducted by the principal
researcher (Michalski, A) and included all published
articles up to November 2011 using Medline, Scopus,
Cinahl, Web of Science and Embase databases with the
keywords listed in Table 3. Keywords varied between
different databases to ensure they identified appro-
priate articles, depending on the search strategy of
a particular database. A total of 3378 articles were
identified. All articles were exported into Endnote®
(Thomson Reuters, New York, NY, USA), a bibliogra-
phic software package, to manage the search results.
Table 2. Inclusion criteria for selecting studies in this review
Types of studies • QA departmental
• Retrospective or prospective or audits
• Human studies
• Tangential or intensity modulated radiation therapy
treatment technique
• English language
• Published articles in referred journals
Types of • Females
participants • Radical treatment intent and prescription
• Photon radiation
• Breast or chest wall radiation treatment
• Supine positioning technique
Types of outcome • Quantitative measurements of inter- or intra-fraction
measures motion
• Reporting on random and/or systematic error
• Electronic portal images or port films
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Table 3. Search keywords

Keywords A (n = 22) Keywords B (n = 16) Keywords C (n = 18 )

Terms related to quality control in Terms related to intra-fraction Terms related to inter-fraction movement
radiation therapy for breast cancer motion due to respiration in due to daily reproducibility in
radiation therapy for breast cancer radiation therapy for breast cancer

1. breast cancer 1. breast cancer 1. breast cancer

2. radiation therapy 2. radiation therapy 2. radiation therapy
3. radiotherapy 3. radiotherapy 3. radiotherapy
4. 1 and 2 or 1 and 3 4. 1 and 2 or 1 and 3 4. 1 and 2 or 1 and 3
5. intensity modulated radiation therapy 5. motion 5. placement error
6. tangential technique 6. respiration 6. variability
7. 3D conformal radiation therapy 7. breathing 7. set-up error
8. 1 and 5 or 1 and 6 or 1 and 7 8. movement 8. inter-fraction
9. gating 9. intra-fraction or intrafraction 9. movement
10. breath hold 10. internal margin 10. stabilisation
11. quality assurance 11. immobilisation 11. whole breast treatment
12. online portal imaging 12. tumour (tumor) motion 12. visual guidance
13. EPID 13. 4 and 5–12 13. set up verification
14. portal imaging 14. patient positioning
15. treatment verification 15. immobilisation
16. quality control 16. reproducibility
17. accuracy 17. patient movement
18. cone beam imaging 18. 4 and 5–16
19. kV imaging
20. IGRT
21. 4 and 9–20
22. 8 and 11 or 8 and 16

EPID, electronic portal imaging device; kV, kilovoltage; IGRT, image-guided radiation therapy.

Articles were excluded based on title and abstract

review. The full texts of the remaining articles were
then reviewed, and their reference lists were hand-
searched for other relevant studies. A replication of the
search strategy was conducted by two other research-
ers (Cox, J and Atyeo, J) to avoid bias and ensure
thorough and relevant inclusion of articles.
Data analysis
Articles that were included in the systematic review were
analysed on their outcome measures to determine if a
meta-analysis could be performed. Articles where it was
not clearly stated how measurements were obtained
were not considered for review. All results were placed
in a table, and a statistician was consulted to assist
with data analysis. Where a measurement for medial and
lateral tangential fields was reported separately, these
were averaged before calculating the results of the
systematic review. Where authors reported two meas-
urements for the same parameter because of different
set-up positioning, these values were entered independ-
ently into the systematic review. Due to the large range
of measurements and terms used in the reviewed arti-
cles, decisions were made as to uniform reporting of the
results.
Definition of terms
Average movement
Although none of the authors describe in any depth the
methods they used for measuring and reporting the
various parameters, it is understood that for each image
acquired for each patient, a measurement of central lung
distance (CLD), central irradiated width (CIW), central
beam edge to skin distance (CBESD), cranio-caudal dis-
tance (CCD) and/or central breast distance (CBD) was
taken. The authors of the articles included in this review
have used the term ‘standard deviation’ to express
random error, whether measured across a full course of
treatment as inter-fraction error, or during one treat-
ment beam as intra-fraction error. The statistical term
‘standard deviation’ implies a variability of scores around
a mean, so a standard deviation (SD) is usually reported
with the mean. However, this is not the case in these
articles, with only the SD being reported for each para-
meter of random inter- and intra-fraction motion. This is
because reporting a mean measurement for each para-
meter would be irrelevant, as each patient is a different
size and shape. A mean would therefore have been
determined solely to calculate the SD but not reported.
SD is hence calculated to depict the variability in

© 2012 The Authors

502 Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists

treatment position for each patient, which gives a rep-
resentation of the magnitude of error. SDs can then be
combined to give a pooled or population variance and
SD, which is usually weighted according to the number
of images taken per patient per day. This gives more
weight to the patients with a larger number of images,
hopefully minimising the effect of outliers on the overall
result. It is this weighted pooled SD that is represented
in the results. To reduce confusion by reporting an SD
without reporting a mean, the term ‘standard deviation’
has been replaced in this review by the term ‘average
movement’. It must be remembered that these values
still behave as an SD, and the results in this review are
given to one SD, with ⫾1SD representing approximately
68% of all cases and ⫾2SDs representing approximately
95% of all cases.
Maximum deviation
A maximum deviation is the largest deviation for the
CLD, CIW, CBESD and/or CCD parameters measured on
the treatment verification image for any patient on any
day. For random error, this is calculated as the largest
difference between the measurement of a parameter on
any of the images obtained and the average measure-
ment of that parameter for the patient. Maximum devia-
tion for systematic error is calculated as the largest
difference between any image obtained and the planning
reference image. This review reports on the range of
maximum deviations, which is the smallest maximum
deviation and the largest maximum deviation in any
direction observed in the included articles.
Minimum and maximum variation (1SD)
Fein et al.7 report the minimum and maximum variation
(1SD) instead of a maximum deviation. In the case
of intra-fraction motion, the SD of each parameter
is calculated for each day. The minimum variation is
the smallest SD observed on any given day, and the
maximum variation is the largest SD of all patients
observed. For inter-fraction motion, an SD is calculated
for each parameter over the course of treatment for each
patient. The minimum variation is the smallest SD for
any patient over the course of their treatment, and the
maximum variation is the largest SD observed. This type
of measurement has not been included in this review, as
this was the only paper to report this measurement.
Average difference
Average difference, also commonly called systematic
error, is recorded for systematic inter-fraction error. This
is a mean value and is reported with an SD to represent
the variability of the scores around the mean. The
average difference is reported as either positive or nega-
tive to indicate the direction of the error. In this review,
© 2012 The Authors
Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists
Motion during breast radiotherapy
average difference will be reported as a range and
average. The range of average difference is from the
smallest difference to largest difference of all the
included articles. The positive and negative signs will be
ignored when we wish to represent the magnitude of
motion but not the direction. The average differences
from all the included articles will be averaged to give
an overall average difference. The positive and negative
signs will be maintained in this calculation. The range of
SDs, to express variability, and maximum deviations will
also be reported.
Results
Eighteen articles were identified for inclusion in the
review, published from 1991 to 2008. The authors of the
included articles reported on intra-fraction motion, sys-
tematic and random inter-fraction motion or a combina-
tion of these. EPIs, portal films, kV images or CBCT were
used to measure the magnitude of error. This was done
either by measuring anatomical landmarks on the image
with respect to field borders on central axis such as CLD,
CIW, CBESD and CCD, or measuring from anatomical
landmarks to the isocentre. A number of terms are
used to record the magnitude of motion reported in
these articles. Due to the large variation in reporting
of outcome measures, a meta-analysis could not be
performed. Unless otherwise specified, images were
taken using MV imaging techniques. These images are
predominately two-dimensional (2D) tangential images,
which present a problem in quantifying the error. An
error in one direction, for example, the CLD may not be
due to the depth but an error in the CCD.
Patient positioning
Each author utilised different patient positioning tech-
niques when treating and collecting images for inter-
and intra-fraction motion. The use of immobilisation
devices can influence the inter- and intra-fraction motion
observed. The set-up techniques for all the included
articles are listed in Table 4.
Table 4. Patient positioning technique outlined in each included article
Patient positioning
Breast board (five articles)†7,37–40
Alpha cradle (two articles)†7,9
Vacuum or foam moulded (three articles)‡38,41,42
Other arm support (seven articles)‡5,43–48
No immobilisation (two articles)‡45,49
No patient set-up described (two articles)17,50
†Fein et al.7 used both breast board and alpha cradle. ‡Thilmann et al.45
and Nalder et al.38 describe immobilisation and no immobilisation
techniques.
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Table 5. Combined results for the magnitude of intra-fraction motion in breast cancer patients

Parameter Combined results

(mm)
Range of average Average Range of maximum
movement – 1SD movement – 1SD deviation†

CLD (five articles)5,7,39,47,49 0.7–1.8 1.19 1.5–13.1

CBESD (five articles)5,7,39,47,49 0.73–2.1 1.26 1.6–14.9
CCD (three articles)5,47,49 0.9–3.2 1.82 2.0–25.6

†Fein et al.7 and Kron et al.39 do not report a maximum deviation.

CBESD, central beam edge to skin distance; CCD, cranio-caudal distance; CLD, central lung distance;
SD, standard deviation.

reported using CLD, CIW, CBESD, CCD and/or CBD

Intra-fraction motion – random error
Seven groups reported on the magnitude of intra-
fraction motion in breast cancer patients. These included
a total of 73 patients and more than 10 000 images. Six
authors reported on the magnitude of motion using CLD,
CBESD and/or CCD measurements, and one measured
isocentre shifts. Table 5 shows the range of average
movement, the average movement and the range
of maximum deviations for five of the seven articles
where results were calculated using the same statisti-
cal methods. Intra-fraction motion in the remaining
two articles was calculated using different statistical
methods. Smith et al.9 reported a maximum range of
intra-fraction motion of 2.5 mm in the CLD and a
maximum deviation from the mean of 2.4 mm. Bohmer
et al.,43 using an isocentric matching technique, found
a mean lateral shift of 1.9 mm, a longitudinal shift of
1.4 mm and a rotational error of 0.8° for five patients
during one fraction resulting in a total of 130 EPIs.
measurements using identical statistical analysis. The
range of average movement, the average movement
and the range of maximum deviations can be seen in
Table 6. Smith et al.9 reported a maximum range for
any patient of 29.4 mm, a maximum deviation from the
mean of 16.2 mm and maximum deviation from the
median of 16.1 mm for CLD.
Inter-fraction motion – systematic error
Nine groups reported on systematic error in 192 breast
cancer patients. For inter-fraction systematic error, the
measurements of CLD, CIW, CBESD and/or CCD are
averaged across the treatment course of a patient. The
range of average difference, the mean average differ-
ence, the range of SDs and the range of maximum
deviations in the CLD, CIW, CBESD and CCD can be seen
in Table 7.

Inter-fraction motion – random error
Nine groups reported on inter-fraction motion in a total
of 170 breast cancer patients. In eight of the nine
articles, the magnitude of inter-fraction motion was
Isocentre shift
Six groups reported on random and systematic inter-
fraction motion in 148 patients, using isocentre shifts
in the ventro-dorsal and cranio-caudal directions. As
the ventro-dorsal measurements were obtained from

Table 6. Combined results for the magnitude of inter-fraction motion (random error) in breast cancer
patients

Parameter Combined results

(mm)
Range of average Average Range of maximum
movement – 1SD movement – 1SD deviations†

CLD (eight articles)5,7,39,40,45–47,49 1.7–4.4 2.21 2.6–11.6

CIW (three articles)46,47,49 0.81–2.9 1.9 3.6–18.2
CBESD (six articles)5,7,39,46,47,49 0.63–4.4 2.20 3.05–15.6
CCD (five articles)5,45–47,49 0.6–4.0 2.6 3.6–22.9
CBD (three articles)7,39,40 2.62–3.7 3.18 NA

†
Fein et al.,7 Kron et al.,39 Pradier et al.46 and Koseoglu et al.40 do not report a maximum deviation.
CBESD, central beam edge to skin distance; CBD, central breast distance; CCD, cranio-caudal
distance; CIW, central irradiated width; CLD, central lung distance; SD, standard deviation.

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 Motion during breast radiotherapy

Table 7. Combined results for the magnitude of systematic error in breast cancer patients

Parameter Combined results

(mm)
Range of average Average Range maximum
difference (SD)† difference deviations‡

CLD (eight articles)5,7,40,42,45–47,49 0.03 (3.9)–4.0 ( – ) 2.42 2.2–20

CIW (three articles)46,47,49 0.98 (3.6)–3.3 (2.6) 1.99 7.6–16.3
CBESD (five articles)5,7,46,47,49 1.94 (3.3)–3.4 (4.3) 2.49 6.9–14.1
CCD (five articles)5,45–47,49 0.63 (3.8)–4.2 ( – ) 1.92 4.6–17.7

†Results reported as mean and (SD). ‡Van Tienhoven et al.,5 Fein et al.7 and Koseoglu et al.40do not
report maximum deviations.
CBESD, central beam edge to skin distance; CCD, cranio-caudal distance; CIW, central irradiated
width; CLD, central lung distance; SD, standard deviation.

tangential images, the ventro-dorsal shifts will be influ-

enced by any medio-lateral error. Four groups also
reported on rotational errors. The range and average
movement of the random and systematic errors can be
seen in Table 8.
Two groups reported on random and systematic
inter-fraction motion using kV imaging techniques. One
acquired daily CBCT for 10 patients matched to the
planning scan using a combination of skin contour and
bony anatomy.37 The second author acquired kV images
for 25 patients for an average of 13 fractions matched to
bony anatomy.17 The average difference and average
movement for each group is presented in Table 9.
Discussion
This review has been able to combine the results of
17 years of data relating to motion during breast radio-
therapy. Each of these studies only has small sample
sizes in terms of subjects, but this still involved review-
ing hundreds of images. Not all groups reported on the
same measurements, or used the same method, reduc-
ing the number of articles that could be combined. Large
variations in ranges and maximum deviations can be
attributed to different patient immobilisation methods
in the studies. In departments where there is no or
limited patient immobilisation, the average difference

Table 8. Combined results for the magnitude of inter-fraction motion (systematic and random error) in breast cancer patients using isocentre shifts

Parameter Combined results

(mm)
Range of average Average Range of average Average
difference (SD):† difference: movement:‡ movement:

Ventro-dorsal shift (x-axis) (six articles)38,41,43,44,48,50 0.1 (4.8)–4 ( – ) 2.49 2.0–3.0 2.43
Cranio-caudal shift (y-axis) (six articles)38,41,43,44,48,50 0.02 (5.0)–15.5 (5.8) 3.65 1.05–5.8 3.13
Rotation (four articles)38,43,48,50 0.08 (1.8)–1.75 (2) 0.62 1.1–2.0 1.55

†Results reported as mean (SD). ‡Valdagni et al.50 and Bohmer et al.43 did not report on random error.
SD, standard deviation.

Table 9. Magnitude of inter-fraction motion (random and systematic error) in breast cancer patients using
kV imaging techniques

Parameter Jain37 Lawson17

(mm)
Average Average Average Average
difference movement: difference (SD)† movement

Lateral 5.7 3.9 1.4 (3.1) 5.2

Longitudinal 2.3 3.2 -0.9 (3.7) 4.8
Vertical 2.8 3.5 0.6 (4.1) 4.2

†Reported as mean (SD).

SD, standard deviation.

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Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists 505
A Michalski et al.
and average movement identified in the review might be
larger. For this reason, it is suggested that each depart-
ment still assess their own patient positioning techniques
using the results in this review as a baseline.
Inter- and intra-fraction motion are small, with
average movement never exceeding 5 mm. Intra-
fraction motion is smaller than inter-fraction motion,
with little difference between random and systematic
error. Average inter- and intra-fraction motion of these
magnitudes have very little clinical impact on breast
radiation therapy, with all authors concluding that such
magnitude of motion during treatment would meet their
departmental protocol. Although infrequent, there were
authors who reported large maximum deviations in
inter- and intra-fraction motion across different patients.
Such deviations could have clinically significant implica-
tions, suggesting a need for daily IGRT. This could be
related to individual patient factors such as movement
during treatment or to difficulties in reproducing and
stabilising the patient throughout treatment. Although
no further information would be gained from further
research into the magnitude of motion using MV
imaging, the dosimetric impact of this motion still needs
to be investigated, particularly as newer techniques such
as IMRT, FIF, VMAT and tomotherapy are introduced.
A clinical target volume–PTV margin of 5 mm is recom-
mended for all whole breast radiotherapy. If margins
are to be reduced, then inter- and intra-fraction motion
should be minimised.
Inter-fraction motion can be minimised when treating
breast cancer through the use of adequate immobilisa-
tion and IGRT. Intra-fraction motion can be minimised
through DIBH techniques where radiation is only deliv-
ered while the patient holds their breath at moderate
to maximum inhalation, thus minimising intra-fraction
motion.
Dosimetric impact
Harron et al.51 found that when treating with a tangential
beam arrangement, a shift of ⱕ5 mm or a rotation error
of ⱕ2° would not cause more than a 5% change in the
target volume receiving between 95% and 107% of the
prescribed dose. They also found that plans that have
larger hot or cold spots are more susceptible to dosimet-
ric changes related to set-up error, which emphasises
the importance of optimising and evaluating breast
plans51 as well as maintaining rigorous stabilisation. This
suggests that IMRT, FIF, VMAT or tomotherapy plans,
which increase homogeneity by removing hot and cold
spots, would be less susceptible to dosimetric changes.
Jain et al.37 reported that their IMRT technique improved
dose homogeneity compared with a standard tangential
technique, and, as a consequence, IMRT plans were
superior to the conventional tangential beam arrange-
ment when the effect of inter-fraction motion was com-
pared with the initial plan. However, the IMRT technique
506 Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists
reported in this article is a hybrid technique where 80%
of the beam is weighted through open tangential fields
and 20% from IMRT fields optimised by the treatment
planning system.37 Similarly to FIF, this technique
reduces the effect that inter- and intra-fraction motion
would have on the dose distribution when compared with
complete IMRT.52 For inter-fraction motion, Goddu
et al.53 found that shifts of only 3 mm in the postero-
medial directions significantly altered dose distributions
in breast patients being treated with helical tomo-
therapy. Uncorrected set-up inaccuracies reduced the
minimum dose to the PTV on average by 4.7 Gy and the
overall average dose by 3.6 Gy.53 An IMRT, VMAT or
tomotherapy plan to the breast may be able to reduce
hot and cold spots and improve dose homogene-
ity,18,19,23,25,54,55 but they use smaller field sizes than a
tangential beam technique, so movement is more likely
to have a large impact on the dose distribution.
For intra-fraction motion, Yu et al.34 simulated the
relationship between dynamic MLC motion and breathing
and found large changes in dose distributions resulting in
geometric misses of the target volume. George et al.56
also found that dose homogeneity to the breast using
IMRT decreased as intra-fraction motion increased, but
there was no significant difference in dose distribution
during a simulation comparing no movement, shallow
breathing or normal breathing. Bortfeld et al.57 also
suggest the main effect of organ motion in IMRT is an
averaging of the dose distribution over the course of
treatment. These papers suggest that inter-fraction
motion has a larger effect on dose distributions than
intra-fraction motion.
Image-guided radiation therapy
IGRT allows for daily online matching and adjustments
to a tolerance of 0 mm, which would reduce inter-fraction
motion and allow the large maximum variations observed
in some patients to be monitored and adjusted on a daily
basis. A CBCT allows 3D information to be obtained
about patient positioning and preliminary results have
shown patient movements to be similar to those meas-
ured using EPIs and port films.37 A comparative study
of daily EPIs to CBCT found that EPIs underestimated
the actual bony set-up error in breast cancer patients
by 20–50% and CBCT significantly decreased setup
uncertainties.58 This suggests a need for further study in
the use of CBCT for whole breast radiation treatment.
PBI
The PTV in PBI is limited to the surgical cavity plus a
margin, resulting in small field sizes during treatment.
The tight margins around the tumour bed in PBI com-
pared with whole breast radiotherapy mean that inter-
and intra-fraction motion can result in large changes
to planned dose distributions with the potential to
© 2012 The Authors

under-dose the tumour bed. To improve accuracy in
localisation of the PTV in PBI, fiducial markers are
inserted around the surgical cavity and offer more accu-
rate localisation than tattoo or bony anatomy-based
set-up.35,59 Using daily pre- and post-kV imaging, intra-
fraction motion of the cavity is on average greater than
4 mm when matched using fiducials, which is larger than
bony anatomy matching, with an average intra-fraction
motion of 2.5 mm.35 When used together with daily
IGRT, fiducial markers allow improved treatment accu-
racy in PBI techniques by taking into account true
inter- and intra-fraction motion.35,59,60
Optical guidance systems have also been used to
measure inter- and intra-fraction motion for whole and
partial breast radiotherapy.12–14 Inter-fraction motion fell
within a root mean square distance of 2.3 mm, although
some large discrepancies in individual patient positioning
were also observed.14 Intra-fraction motion revealed
position shifts of 2–3 mm.12–14 These results are similar
to those achieved using EPIs, port films or kV imaging,
so optical systems could act as a surrogate to EPI or kV
imaging.13
Immobilisation versus no immobilisation
Three articles included in this review described the effect
of immobilisation versus no immobilisation. Two of these
found that adequate immobilisation, such as the use of a
patient support device, reduced random and systematic
inter-fraction error.44,45 Mitine et al.44 found that a fixed
arm support and treatment being delivered by a team
that spent additional time in preparation and setting up
patients led to a reduction in the number of large devia-
tions >10 mm, especially in the cranio-caudal direction.
Thilmann et al.45 also reported significantly improved
reproducibility with the use of an immobilisation device.
In contrast, Nalder et al.38 used customised vacuum-
moulded bags for immobilisation of the patients and
found that there was no significant improvement in
reproducibility with the use of this immobilisation, con-
cluding that they would not implement it into their
department. On the other hand, they noted that a higher
percentage of patients found their positioning during
treatment and simulation to be more comfortable with
the use of the immobilisation device.
Conclusion
No further research into the magnitude of inter- and
intra-fraction motion is necessary. However, depart-
ments that have no immobilisation for their breast
patient set-up should perform their own evaluation of
the magnitude of motion in their department and
compare results with this review. Inter-fraction motion is
larger than intra-fraction motion, but the average mag-
nitude of movement is generally very small and similar
across a number of the studies reviewed. PTV breast
© 2012 The Authors
Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists
Motion during breast radiotherapy
margins of 5 mm are considered acceptable as most
inter- and intra-fraction motion is less than 5 mm. Daily
imaging is suggested for all breast cancer treatment as
maximum variations for some patients can be quite
large and difficult to predict. With the implementation of
modulated techniques and PBI, daily imaging is essen-
tial. Future research into the placement of surgical clips
and kV imaging in the radiation treatment of breast
cancer can use the results from this study to compare
differences in bony matching to matching using surgical
clips. Further research into the dosimetric impact on
cardiac and lung doses from inter- and intra-fraction
motion is also warranted.
Acknowledgement
We would like to thank Dr Robert Heard, Senior Lecturer
at the University of Sydney, for assisting in the statistical
analysis.
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