Acta Oncologica, 2012; 51: 333–344

ORIGINAL ARTICLE

Radiation during deep inspiration allows loco-regional treatment

of left breast and axillary-, supraclavicular- and internal mammary
lymph nodes without compromising target coverage or dose
restrictions to organs at risk

MARI H. B. HJELSTUEN, INGVIL MJAALAND, JOHAN VIKSTRÖM &

KJELL IVAR DYBVIK

Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway

Abstract
Background and purpose. Loco-regional radiotherapy of left-sided breast cancer represents a treatment planning chal-
lenge when the internal mammary chain (IMC) lymph nodes are included in the target volume. This treatment plan-
ning study evaluates the reduction in cardiopulmonary doses when radiation is given during deep inspiration
breath-hold (DIBH). This was achieved without compromising dose coverage to the planning target volume (PTV).
Patients and methods. Seventeen patients with early breast cancer, referred for adjuvant radiotherapy, were included.
For each patient two computed tomography (CT)-scans were acquired; the first during free breathing (FB) and the
second during DIBH. The scans were monitored by the Varian RPMTM respiratory gating system. Audio-visual guid-
ance was used. The treatment planning of the two CT studies was performed focusing on good coverage (V95% ⬎ 98%)
of the PTV. Doses to the heart, left anterior descending (LAD) coronary artery, lungs and contralateral breast were
assessed. Results. With equal PTV coverage, average mean heart dose was reduced from 6.2 Gy to 3.1 Gy in DIBH
plans as compared to FB. Average volume receiving 25 Gy or more (V25Gy) was reduced from 6.7% to 1.2%,
and the number of patients with V25Gy ⬎ 5% was reduced from 8 to 1 utilizing DIBH. The average mean dose to the
LAD coronary artery was reduced from 25.0 Gy to 10.9 Gy. The average ipsilateral lung volume receiving 20 Gy or
more (V20Gy) was reduced from 44.5% to 32.7% with DIBH. In 11 of the DIBH plans V20Gy was lower
than 35%, in accordance with national guidelines, while none of the FB plans fulfilled this recommendation.
Conclusion. Respiratory gated radiotherapy during DIBH is a suitable technique for loco-regional breast irradiation
even when IMC lymph nodes are included in the PTV. Cardiopulmonary doses are considerably decreased for all
dose levels without compromising the dose coverage to PTV.

Loco-regional radiotherapy (RT) of left-sided breast
cancer represents a treatment planning challenge,
especially when the internal mammary chain (IMC)
lymph nodes are included in the target volume. Due
to the increased radiation dose, especially to the
heart, the IMC lymph nodes are often excluded from
the target volume. However, recent studies indicate
increased survival after radiation of IMC lymph
nodes among patients with lymphatic draining to the
IMC lymph nodes [1,2]. Together with the extended
use of cardiotoxic systemic therapy this highlights the
need for improvements in RT delivery to reduce irra-
diation to organs at risk (OAR) and normal tissue.
In recent years different RT techniques, such as
intensity modulated RT (IMRT), volumetric modu-
lated arc therapy (VMAT), tomotherapy and respira-
tory gating have been introduced as possible treatment
strategies to reduce the cardiopulmonary doses.
Several authors [3–5] have shown that respiratory
gating reduces the cardiopulmonary doses when irra-
diating during deep inspiration. Deep inspiration
increases the distance between the breast and the
heart due to increased lung volume, and the heart is
partially or completely moved out of the high dose
region. The relative volume of the ipsilateral lung
exposed to irradiation is also decreased. In a recent
treatment planning study we were able to show that
radiation during deep inspiration breath-hold (DIBH),

Correspondence: Mari H. B. Hjelstuen, Department of Hematology and Oncology, Stavanger University Hospital, Pb 8100, 4068 Stavanger, Norway.
Tel: ⫹ 47 51519053. Fax: ⫹ 41 51519045. E-mail: hjem@sus.no

(Received 2 March 2011; accepted 24 August 2011)

ISSN 0284-186X print/ISSN 1651-226X online © 2012 Informa Healthcare
DOI: 10.3109/0284186X.2011.618510
334 M. H. B. Hjelstuen et al.
utilizing audio-visual guidance of the patient, allows
tangential treatment of left-sided breast cancer
patients with considerably reduced cardiac doses
without compromising target coverage [6].
The purpose of this treatment planning study was
to carefully evaluate the dose to OAR for patients
with left-sided breast cancer when irradiating the
breast and loco-regional lymph nodes in the axilla,
supraclavicular region and IMC during free breath-
ing (FB) and DIBH, respectively. The inclusion of
axillary levels, supraclavicular region and the IMC
was done for scientific purposes only in order to test
our DIBH technique in a “worst case” scenario. To
our knowledge, this is the first study with a reason-
able number of patients that documents good and
similar dose coverage to the planning target volume
(PTV) for both techniques to be compared. Equal
PTV dose coverage is important when comparing the
dose to OAR. In contrast to others who have used
the DIBH technique, we gave our patients audio-
visual guidance to reach the same amplitude level
at each deep breath, and to maintain very stable
amplitude within each breath-hold.
Patients and methods
Patient population
Computed tomography (CT) series of 17 patients
who were referred for adjuvant RT after breast con-
serving surgery at Stavanger University Hospital
between January and October 2006 were analyzed.
The inclusion of patients was not consecutive, but
based on logistics availability (staff and venues).
Twelve of these patients had left-sided and five had
right-sided breast cancer, but for study purposes the
mammary glandular tissue and lymph nodes in the
Figure 1. A typical DIBH breathing curve from CT-scanning, with gaps of FB between each DIBH. The CT-scan was acquired during
one DIBH (pink area) and the gating window (green lines) was set to the mean amplitude ⫾ 1 mm. CT, computed tomography; DIBH,
deep inspiration breath-hold; FB, free breathing.
axilla, supraclavicular region and the IMC of the left
side were defined as the target in all patients. The
median age was 60 (range: 29–70) years. The patients
had to be able to cooperate and to hold their breath
for 15–20 s. The study was approved by the regional
ethical committee as a project for quality assurance
in health care. The CT series were taken prior to the
clinical implementation of the DIBH technique, and
with one exception, the patients were not treated
with respiratory gating.
CT scanning
Two CT series were obtained for each patient, one
during FB and the other during DIBH. The patients
were placed in a supine position with bilateral arm
abduction above the head using a PosiboardTM-2
breast board (CIVCO Medical Solutions, Kalona,
IA, USA). In our department all breast cancer
patients undergoing RT are placed in this treatment
position, independent of laterality and lymph node
involvement. CT-scans were performed at 3 mm
intervals and encompassed both breast and the whole
thoracic cavity including the heart and both lungs.
The image acquisition was in helical mode.
The Varian RPMTM respiratory gating system,
version 1.6 (Varian Medical Systems, Palo Alto, CA,
USA) was used for real time registration of the respira-
tion. An infrared reflecting marker was placed on the
patient, normally over the xiphoid process, and a video
camera registered the anteroposterior motion of the
marker due to respiration. The amplitude of DIBH, i.e.
the chest wall motion was individually set prior to the
CT-scan. The DIBH amplitude was only allowed to
deviate ⫾ 1 mm during the scanning. Figure 1 shows a
typical DIBH breathing curve. The patient received
visual guidance through the binocular head mounted
 Heart and lung doses with DIBH for breast cancer patients
display to sustain reproducibility and stability of the
DIBH amplitude. The scanning time was typically
around 20 s and most patients managed to complete
the scan during one DIBH. For those who did not, the
CT had to be manually stopped, and restarted during
the next DIBH. In this study the mean anteroposterior
(AP) chest wall movement at the position of the xiphoid
process was 3 mm (range: 1.6–5.0 mm) during FB.
With the DIBH technique the chest wall was moving
an average of 18 mm (range: 14.6–27.0 mm) in the
anterior direction when the patients breathed in deeply,
and during breath hold the AP chest wall movement
was only allowed to vary 2 mm.
Delineation of target and OAR
The CT series were transferred to an Eclipse 3-D
treatment planning workstation, version 8.0 (Varian
Medical Systems) and the clinical target volume
(CTV) and OAR were delineated.
The mammary glandular tissue and lymph nodes
in the axilla, supraclavicular region and in the IMC
of the left side were defined as CTV. The internal
mammary nodes located in intercostal space 1 to 3
and nodes of level I, II and III of the axilla were
completely included in the CTV.
The heart, the left anterior descending (LAD)
coronary artery, both lungs and the contralateral
breast were considered OAR. The lung volume was
automatically generated using the auto-contouring
tool of the treatment planning system. The heart
volume was defined as the entire visible myocardium,
including the pericardium, from apex of the heart, to
the right auricle, atrium, and infundibulum of the
ventricle. The ascending aorta, the pulmonary trunk
and the superior vena cava were excluded. The LAD
coronary artery was delineated in the anterior inter-
ventricular groove to the apex of the heart. The con-
tralateral breast was defined as all glandular breast
tissue of the right side.
For consistency, the delineation of CTV and the
contralateral breast was performed by the same oncol-
ogist for all patients. The LAD coronary artery and
the heart were delineated by a radiation technologist.
Delineation of the LAD coronary artery was done
under supervision from a cardiologist, and the delin-
eation of the heart was verified by the oncologist.
The margin from CTV to PTV was 5 mm, except
for superficial areas where PTV was never closer than
5 mm to the skin. The margins were the same for
DIBH and FB. Due to the chosen 2 mm gating win-
dow the movement of the chest wall during the
DIBH plateau was the same, or smaller, as compared
to FB. Hence the margin to compensate for CTV
motion did not have to be increased with the DIBH
technique. OAR were delineated without margins.
335
Treatment planning
An individually optimized mono-isocentric photon
field treatment plan was obtained for each CT
series. The technique included wide opposing
6 MV tangential fields covering the remaining
breast and internal mammary nodes and AP-PA
fields, 6 MV and 15 MV, respectively, covering
the axillary and supraclaviculary nodes, abutting
each other half-beam. Occasionally low weighted
15 MV fields, with the same geometry as the 6 MV
tangential fields, were added. All fields were con-
formal with multileaf collimators and wedges in
some cases. The isocenter was individually deter-
mined, but was equally positioned inside the CTV
in the transition between mammary tissue and
supraclavicular lymph nodes in both CT series, FB
and DIBH, for the same patient.
The following dose constraints were given:
1) Minimum 98% of the PTV should be covered
by the 95% isodose line (V95% ⱖ98%).
2) The 95% isodose line should cover the dorsal
limit of the PTV (by visual inspection).
3) The mean dose to PTV should be close to 100%
of the prescribed dose, and not above 102%.
4) Dose maximum should not exceed 110% and
preferably not 107%.
5) The dose to OAR should be kept as low as pos-
sible, without compromising the PTV dose, i.e.
the criteria of PTV coverage should be fulfilled,
even if the national guidelines for doses to OAR
were exceeded.
For each patient only minor difference between
the two plans, FB and DIBH, with respect to target
dose coverage, dose conformity, maximum dose,
beam energy and geometry, should be accepted.
In a clinical setting the prescribed dose to PTV
is 46 Gy in 2 Gy fractions followed by 4 Gy in 2 Gy
fractions to the left breast only. For simplicity, in
this study the prescription dose was 50 Gy in 2 Gy
fractions to PTV. The dose to heart and ipsilateral
lung is therefore slightly increased, about 0.5%, as
compared to the clinical setting.
National guidelines recommend the following dose
limitation to OAR:
1) The volume of the heart receiving a dose of
25 Gy or more should be smaller than 5%
(V25Gy ⱕ 5%).
2) The volume of ipsilateral lung receiving a dose
of 20 Gy or more should be smaller than 35%
(V20Gy ⱕ 35%).
The guidelines do not have specific recommenda-
tions regarding the dose to contralateral breast and
336 M. H. B. Hjelstuen et al.
LAD coronary artery, except keeping them as low as
possible.
The calculation algorithm used was Eclipse pen-
cil beam (PB) described by Storchi et al. [7] with the
modified Batho inhomogeneity correction [8]. All
plans were made by the same physicist.
Outcome measures and statistical analysis
For each patient cumulative dose-volume histograms
(DVHs) were calculated for all delineated volumes
in the two different treatment plans. Dose to PTV
and OAR was assessed. The volumes, mean and
maximum doses were obtained from the DVH
statistics. The relative volume Vx, irradiated to a
minimum dose x (in Gy or %), e.g. V25Gy for the
heart, V20Gy for the ipsilateral lung and V95% for
PTV, were obtained from the DVH graphs. The
relative dose Dx%, covering minimum x% of the
volume of interest, e.g. D2%, D50% and D98% were
also obtained from the DVH graphs. The maximum
heart distance (MHD) and maximum lung distance
(MLD) were measured in beams eye view.
The homogeneity and conformity indices were
calculated. The homogeneity index (HI) for PTV is
defined as follows [9]:
HI ⫽ (D2%–D98%)/D50%
An HI of zero indicates that the dose distribution is
almost homogeneous.
The target conformity index (CI) as well as the
healthy tissues conformity index (CIHealthy Tissues)
were calculated. The CI is defined as follows [10]:
CI ⫽ (V95%/VPTV)
where V95% is the volume of PTV covered by the
95% isodose line, and VPTV is the volume of PTV.
This equation defines the quality of the coverage of
the target. The index ranges from 0 to 1, where 1
indicates that all of the target volume is covered by
the prescribed dose.
The healthy tissues conformity index is defined
as follows [10], when the reference isodose is set
equal to the 95% isodose:
Table I. Mean volume, in cm3, for planning target volume (PTV) and organs at risk (OAR) during free breathing (FB) and deep inspiration
breath-hold (DIBH) for all 17 patients. Data are shown as mean values with one standard deviation, and range in brackets.
FB
PTV 1362.8 ⫾ 374.7 [843.4–2105.9]
Heart 616.5 ⫾ 75.5 [460.7–750.7]
LAD coronary artery 1.0 ⫾ 0.6 [0.2–2.5]
Ipsilateral lung 1178.2 ⫾ 343.2 [630.0–1978.6]
Total lung 2635.2 ⫾ 693.4 [1482.3–4246.6]
Contralateral breast 631.5 ⫾ 295.2 [252.9–1282.4]
LAD, left anterior descending.
*Significantdifference (p ⬍ 0.05) between FB and DIBH.
CIHealthy Tissues ⫽ (V95%/TV95%)
where TV95% is the volume of the 95% isodose. This
equation defines volume of healthy tissue receiving a
dose greater than or equal to 95% of the prescribed
dose. The CIHealthy Tissues ranges from 0 to 1, where 1
is the ideal value (perfect conformation).
The distance from isocenter to the cranial limit of
CTV was obtained from the CT series, by counting
the number of CT slices from isocenter to the last
cranial slice with CTV delineation, and multiply by
the slice thickness of 3 mm. Similarly, the distances
from isocenter to the cranial limit of the lung and the
mammary tissue of the left side as well as the caudal
limit of CTV in the IMC region were obtained.
Paired Wilcoxon test was used for statistical
analysis of the differences with computer software
SPSS version 16.0. Data were considered statistically
significant for p ⬍ 0.05.
Results
PTV and OAR volumes
Table I shows the mean volume of PTV and OAR
during FB and DIBH for all 17 patients. Com-
pared to FB, the mean volume of ipsilateral
lung increased about two-fold during DIBH
(1178.2 cm3 vs. 2165.1 cm3, p ⬍ 0.001), while the
mean heart volume decreased about 10% in size
(616.5 cm3 vs. 559.8 cm3, p ⫽ 0.003). For the
other delineated volumes no significant difference
in size was found.
Figure 2 shows the CTV, the mammary tissue
and the ipsilateral lung for the same patient during
FB and DIBH. The position of the isocenter inside
the CTV was identical for the two CT series, 1.24
cm caudally to the cranial border of the mammary
tissue. As shown in Figure 2 the shape and position
of CTV was somewhat changed during DIBH com-
pared to FB. The CTV was moved cranially during
DIBH with the isocenter position (mean: 0.82 cm)
closer to the apex of the lung. During DIBH the
length of the supraclavicular region was reduced with
1.12 cm (mean value, p ⬍ 0.001) whereas the length
DIBH p-value
1346.4 ⫾ 365.0 [879.4–2074.0] 0.163
559.8 ⫾ 72.2 [458.1–676.0] 0.003*
1.0 ⫾ 0.4 [0.6–1.8] 0.253
2165.1 ⫾ 509.9 [1229.3–3249.7] ⬍ 0.001*
4676.3 ⫾ 1010.9 [2634.7–6763.8] ⬍ 0.001*
627.4 ⫾ 303.3 [250.1–1298.1] 0.301
 Heart and lung doses with DIBH for breast cancer patients 337

Figure 2. CTV (translucent green), mammary tissue (pink) and ipsilateral lung (yellow) for the same patient during FB (left) and DIBH
(right). The yellow line shows the craniocaudal position of the isocenter. The white arrows show the measured distances from isocenter
to the caudal limit of the internal mammary nodes (A), from isocenter to the cranial limit of CTV (B), from isocenter to cranial limit of
the ipsilateral lung (C), as well as the distance from isocenter to the cranial limit of the mammary tissue (D). CTV, clinical target volume;
DIBH, deep inspiration breath-hold; FB, free breathing.

of the IMC region was increased with 0.67 cm the DIBH plans (0.62 vs. 0.64 in FB plans,
(p ⫽ 0.042) as compared to FB. p ⫽ 0.006).

Treatment planning and PTV coverage Organs at risk

The dose distribution and a beam’s eye view of the
medial tangential field for both plans for the same
patient are shown in Figure 3. The figure shows that
the lungs greatly increase in volume during deep inspi-
ration, separating the heart from the chest wall. In
addition, the heart moves caudally as the lungs push
the diaphragm downward. Thus, the heart is moved
out of the beam portals and the high dose region.
The mean DVHs for FB and DIBH, averaged for
all 17 patients, for PTV are shown in Figure 4. The
DVHs for PTV were quite similar in DIBH and FB
plans reflecting a similar and homogeneous PTV
coverage. The treatment planning results are sum-
marized in Table II. All plans fulfilled the criterion of
dose coverage to the PTV as described in methods.
There was no difference in average mean dose, D98%
and V95% for PTV in FB and DIBH, whereas aver-
age D2% was slightly higher in the DIBH plans (53.2
Gy vs. 53.0 Gy in FB plans, p ⫽ 0.006).
No statistical differences were seen in mean HI
and mean target CI in FB and DIBH plans. The
CIHealthy Tissue, however, were significantly lower in
The mean DVHs for FB and DIBH, averaged for all
17 patients, for the OAR, are shown in Figure 4. The
mean DVHs show that the low-, medium- as well as
the high dose region in the heart, the LAD coronary
artery and the ipsilateral lung were reduced with
DIBH. For the contralateral breast the mean DVHs
indicate that the volumes of low and medium doses
were slightly increased with the DIBH technique.
The OAR treatment planning results are listed in
Table II.
Cardiac doses
All treatment plans based on FB technique included
heart tissue within the beam portals (Table II).
With the DIBH technique the heart was completely
outside the beam portals for seven of the 17 patients
(41.2%). The average MHD decreased from 1.9 cm
(range 0.9–3.7 cm) using FB to 0.7 cm (range 0.0–
3.4 cm) using DIBH. The average mean heart dose
was reduced from 6.2 Gy (range 2.5–14.4 Gy) to 3.1
Gy (range 1.8–9.7 Gy) with the DIBH technique.
338 M. H. B. Hjelstuen et al.

Figure 3. The upper panel shows the dose distribution in a transversal CT slice obtained at the same position of PTV for the same
patient during FB (left panel) and DIBH (right panel), respectively. The heart moves out of the high dose region during DIBH. The
lower panel shows beam’s eye views of the medial tangential field during FB (left) and DIBH (right) for the same patient as upper
panel. During inspiration the lung volume (blue) is increased, the breast (red) is moved cranioventrally and the heart (pink) caudally.
In the shown case, the heart and the LAD coronary artery (green) was not included in the beam portal (yellow lines) during DIBH.
CT, computed tomography; DIBH, deep inspiration breath-hold; FB, free breathing; LAD, left anterior descending; PTV, planning
target volume.

Both of these differences were significant (p ⬍ 0.001).
The mean V25Gy was significantly decreased in the
DIBH plans (1.2% vs.6.7% with FB, p ⬍ 0.001).
Scatter plot of V25Gy in FB and DIBH plans for
each patient are shown in Figure 5. V25Gy was larger
than 5% in eight patients (47.1%) using the FB tech-
nique, compared to only one patient (5.9%) when
using DIBH (Figure 5). The largest V25Gy value
observed was 23.0% for FB and 11.5% for DIBH.
These values were not from the same patient. The
patient with the largest V25Gy value (23%) during
FB achieved a V25Gy of 2.2% with the DIBH tech-
nique. Average D2% for the heart was reduced from
34.1 Gy in FB plans to 13.1 Gy in DIBH plans
(p ⬍ 0.001).
For the LAD coronary artery there was a signifi-
cant (p ⬍ 0.001) reduction in average mean dose
from 23.0 Gy (range 3.7–48.2 Gy) to 10.9 Gy (range
3.1–38.9 Gy). Mean V25Gy for the LAD coronary
artery was also significantly reduced, from 48.4%
with FB to 14.1% with DIBH (p ⫽ 0.001). Average
D2% for the LAD coronary artery was reduced
(p ⬍ 0.001) from 39.2 Gy (range 5.1–50.1 Gy) to
24.1 Gy (range 4.0–47.8 Gy).
Pulmonary doses
Average mean dose to the ipsilateral lung was 5.3
Gy lower with DIBH than with FB (16.4 Gy vs.
21.7 Gy, p ⬍ 0.001). Similarly, the average V20Gy
for ipsilateral lung was significantly reduced from
44.5% (range 35.8–51.2%) using FB to 32.7%
(range 24.5–41.8%) using DIBH (Table II). V20Gy
for each patient individually, FB versus DIBH, is
 Heart and lung doses with DIBH for breast cancer patients 339

Figure 4. Mean DVHs averaged for all 17 patients for PTV and OAR with FB (solid line) and DIBH (dotted line). DIBH, deep inspiration
breath-hold; DVH, dose-volume histograms; FB, free breathing; OAR, organs at risk; PTV, planning target volume.

plotted in Figure 6. All patients had V20Gy higher
than 35% with FB, whereas this was true only for
six of the 17 patients with DIBH (Figure 6). In FB,
13 patients had V20Gy ⬎ 41.8% which was the
largest V20Gy value observed in DIBH plans.
The average MLD of the medial field increased
from 4.7 cm with FB to 5.1 cm with DIBH
(p ⫽ 0.017). Average mean dose to total lung
volume was reduced with 2.2 Gy using DIBH, from
10.3 Gy (range 8.4–12.1 Gy) with FB to 8.1 Gy
(range 6.5–10.7 Gy) with DIBH (p ⬍ 0.001).
Contralateral breast
Average mean dose to the contralateral breast was 0.5
Gy higher in DIBH plans than in FB plans (2.7 Gy vs.
2.2 Gy, p ⫽ 0.012), and V2Gy was 3.9% larger (26.1%
in DIBH plans vs. 22.2% in FB plans, p ⫽ 0.049).
340 M. H. B. Hjelstuen et al.
Table II. Summary of treatment planning data for PTV and OAR for the 17 breast cancer patients included in this study, with FB and
DIBH. The prescription dose was 50 Gy in 2 Gy fractions. For comparison with earlier studies maximum doses are also shown.
FB DIBH p-value

PTV
Mean (Gy) 50.5 ⫾ 0.3 [50.0–50.9] 50.5 ⫾ 0.3 [50.0–51.0] 0.122
STD (%) 2.6 ⫾ 0.2 [2.2–3.1] 2.7 ⫾ 0.2 [2.4–3.1] 0.022*
Maximum (Gy) 54.0 ⫾ 0.3 [53.4–54.4] 54.3 ⫾ 0.3 [53.8–55.0] 0.001*
D2% (Gy) 53.0 ⫾ 0.3 [52.3–53.5] 53.2 ⫾ 0.4 [52.5–53.7] 0.006*
D98% (Gy) 47.8 ⫾ 0.2 [47.5–48.2] 47.8 ⫾ 0.3 [47.5–48.4] 0.679
V95% (%) 98.9 ⫾ 0.5 [98.1–99.7] 98.8 ⫾ 0.5 [98.0–99.4] 0.868
Homogeneity index 0.10 ⫾ 0.01 [0.09–0.12] 0.11 ⫾ 0.01 [0.09–0.12] 0.055
Conformity index 0.99 ⫾ 0.00 [0.98–1.00] 0.99 ⫾ 0.00 [0.98–0.99] 0.868
Healthy tissues conformity index 0.64 ⫾ 0.04 [0.58–0.71] 0.62 ⫾ 0.04 [0.57–0.70] 0.006*
Heart
Mean (Gy) 6.2 ⫾ 3.6 [2.5–14.4] 3.1 ⫾ 1.9 [1.8–9.7] ⬍ 0.001*
Maximum (Gy) 47.4 ⫾ 4.1 [33.5–51.3] 33.5 ⫾ 13.9 [5.1–49.9] ⬍ 0.001*
D2% (Gy) 34.1 ⫾ 14.2 [7.0–48.8] 13.1 ⫾ 11.9 [3.7–46.2] ⬍ 0.001*
V25Gy (%) 6.7 ⫾ 6.8 [0.1–23.0] 1.2 ⫾ 2.8 [0.0–11.5] ⬍ 0.001*
Number of patients with 8 (47.1%) 1 (5.9%)
V25Gy ⬎ 5%
Median V25Gy (%) 4.8 0.1
MHDa (cm) 1.9 ⫾ 0.9 [0.9–3.7] 0.7 ⫾ 0.9 [0.0–3.4] 0.001*
Number of patients with 0 (0.0%) 7 (41.2%)
MHD ⫽ 0
LAD coronary artery
Mean (Gy) 25.0 ⫾ 14.0 [3.7–48.2] 10.9 ⫾ 9.1 [3.1–38.9] ⬍ 0.001*
Maximum (Gy) 41.0 ⫾ 13.0 [5.4–50.3] 27.1 ⫾ 16.7 [4.2–48.4] 0.001*
D2% (Gy) 39.2 ⫾ 14.0 [5.1–50.1] 24.1 ⫾ 16.3 [4.0–47.8] 0.001*
V25Gy (%) 48.4 ⫾ 36.1 [0.0–99.9] 14.1 ⫾ 22.8 [0.0–84.7] 0.001*
Ipsilateral lung
Mean (Gy) 21.7 ⫾ 2.5 [17.2–24.9] 16.4 ⫾ 2.3 [12.6–21.0] ⬍ 0.001*
V20Gy (%) 44.5 ⫾ 5.0 [35.8–51.2] 32.7 ⫾ 4.8 [24.5–41.8] ⬍ 0.001*
Median V25Gy (%) 42.8 30.4
MLDb of medial field (cm) 4.7 ⫾ 0.6 [3.8–5.8] 5.1 ⫾ 0.6 [4.2–6.0] 0.017*
Number of patients with 17 (100%) 6 (35.3%)
V20Gy ⬎ 35%
Total lung
Mean (Gy) 10.3 ⫾ 1.2 [8.4–12.1] 8.1 ⫾ 1.1 [6.5–10.7] ⬍ 0.001*
Contralateral breast
Mean (Gy) 2.2 ⫾ 1.7 [0.8–7.5] 2.7 ⫾ 2.0 [1.1–8.7] 0.012*
Maximum (Gy) 40.1 ⫾ 16.8 [11.8–54.8] 44.3 ⫾ 14.7 [11.1–54.6] 0.587
D2% (Gy) 13.2 ⫾ 11.8 [2.5–46.5] 16.5 ⫾ 12.4 [3.5–49.0] 0.047*
V2Gy (%) 22.2 ⫾ 16.1 [4.2–58.8] 26.1 ⫾ 16.4 [7.6–63.0] 0.049*

DIBH, deep inspiration breath-hold; FB, free breathing; OAR, organs at risk; PTV, planning target volume.
Data are shown as mean values with one standard deviation, and range in brackets, except for the median values.
aMaximum heart distance.
bMaximum lung distance.

*Significant difference (p ⬍ 0.05) between FB and DIBH.

Average D2% was also slightly increased in the DIBH
plans (16.5 Gy vs. 13.2 Gy with FB, p ⫽ 0.047).
Discussion
In this CT planning study we were able to demon-
strate that irradiation of the left breast and regional
lymph nodes, including the IMC, in a DIBH tech-
nique utilizing audio-visual guidance, leads to a sub-
stantial reduction in cardiopulmonary doses without
compromising target coverage.
Including the IMC lymph nodes in the CTV is
debated, due to conflicting results in outcome gain
and increased risk of cardiac mortality. However,
the results of the Early Breast Cancer Trialists’ Col-
laborative Group (EBCTCG) meta-analysis dem-
onstrate the importance of local treatment on
long-term survival, and the fact that IMC lymph
node treatment was included in 24 of 25 post-mas-
tectomy RT studies included in the meta-analysis
have led to renewed interest in IMC lymph node
treatment of breast cancer [1]. Lymphoscintigraphy
 Heart and lung doses with DIBH for breast cancer patients
Figure 5. Volume of heart (in %) receiving 25 Gy or more
(V25Gy) in FB plans versus DIBH plans plotted for each patient
individually. DIBH, deep inspiration breath-hold; FB, free
breathing.
studies have shown that about one of 25 breast can-
cer patients have IMC lymph node metastases [11],
and that medial tumors are more likely than lateral
tumors to drain to the IMC lymph nodes [1,12].
The incidence of lymph node metastases of the
internal mammary and medial supraclavicular
lymph node chain are reported to be in the range
4–9% in axillary node negative patients and
16–52% for axillary node positive patients [2,13].
Studies on large series of breast cancer patients
have shown that patients who had their tumor
located in the inner portion of the breast had a
significantly worse prognosis than patients with the
tumor in the outer quadrant [14,15], which might
be due to inadequate treatment of IMC lymph
node metastases. Local recurrence in the IMC may
be underdiagnosed, and involvement of the IMC
lymph nodes might lead to spread of cancer to
other regions, such as the pleura and the thoracic
cavity [2]. Several authors emphasize the impor-
tance of including IMC mapping in breast cancer
staging and breast cancer management decision
[1,2,14,15], and recommend radiation treatment
specifically targeting the IMC lymph nodes if it can
be safely administered without significant dose to
the heart and the ipsilateral lung.
Loco-regional RT of left-sided breast cancer
represents a treatment planning challenge when
the IMC lymph nodes are included in the target
volume. In this study a mono-isocentric four-field
wide tangential technique was applied. The wide
tangential fields were necessary to cover the internal
mammary nodes, but increased the volume of heart,
ipsilateral lung and contralateral breast included in
341
the beam portals. In our study the choice of gantry
angle was a compromise between lung and contral-
ateral breast sparing. A deep angle would irradiate
much heart and lung, whereas a shallow angle would
irradiate much of the contralateral breast. During
DIBH, the PTV was moved cranially and the fossa
supraclavicular region was squeezed and became
shorter. The internal mammary region increased
in length (craniocaudally) during DIBH, probably
due to the increased intercostal distance during
inspiration. The AP-PA fields covering the fossa
supraclavicular region were therefore in general
shorter in the craniocaudal direction in DIBH plans
than in FB plans, while the deep tangential fields
covering the IMC region were larger. The ipsilateral
lung saving effect due to smaller AP-PA-fields was
probably cancelled out by the larger wide tangential
beam portals to cover the enlarged IMC region
during DIBH. Thus, the cardiopulmonary dose
reduction observed during DIBH is mostly caused
by the movement of the heart out of the high dose
region and the increased lung volume.
The treatment planning was done with focus on
similar and good PTV coverage (V95% ⬎ 98%) for
both breathing techniques. Good PTV coverage is a
goal in RT, but not always achievable in clinical prac-
tice, where compromising target dose against OAR
is a common challenge. Our study shows the cardio-
pulmonary doses as they would be, with optimal tar-
get coverage without compromises.
The FB and DIBH plans in our study showed
equal and good PTV coverage as measured by V95%
Figure 6. Volume of ipsilateral lung (in %) receiving 20 Gy or
more (V20Gy) in FB plans versus DIBH plans plotted for each
patient individually. DIBH, deep inspiration breath-hold; FB, free
breathing.
342 M. H. B. Hjelstuen et al.
and D98% as well as with HI and CI indices. All
plans fulfilled the strict planning criterion of
V95% ⬎ 98%, and the 95%-isodose was by visual
inspection ensured to cover the dorsal part of PTV
including the internal mammary nodes with margins.
It should be noted that the PB algorithm overesti-
mates the target dose as discussed by Vikström et al.
[6]. In clinical practice it is recommended to use a
modern calculation algorithm with inhomogeneity
corrections that also account for lateral electron scat-
ter, i.e. the analytical anisotropic algorithm (AAA) or
the collapsed cone (CC) algorithm. However, as
most previous studies used the same algorithm, if
stated, the comparison of doses is relevant. Both
plans had a CIHealthy tissue larger than 0.6, and can be
considered to be conformal according to Lomax and
Scheib [16], who defined irradiation to be conformal
if the CIHealthy tissue index was ⱖ0.6. However, the
DIBH plans had a slightly decreased normal tissue
conformity compared to FB plans, due to a 50 cm3
larger TV95%. The increased TV95% as well as the
slightly increased average D2% in the DIBH plans
might be due to the increased photon beam trans-
mission caused by decreased lung density during
DIBH. The difference in the CI between the FB and
DIBH plans is expected to be larger when the AAA
or CC algorithm is used.
The DVHs in Figure 4 demonstrate the great
benefit of the DIBH technique with respect to car-
diopulmonary doses. The volume of heart and lungs
irradiated to high-, medium- and low-dose levels
were considerably reduced with the DIBH technique.
Eleven patients fulfilled the national guidelines with
respect to pulmonary doses using the DIBH tech-
nique without compromising the PTV coverage,
whereas no patients did using the FB technique.
Average mean heart dose was halved and only one
patient had V25Gy ⬎5% with DIBH. However, all
patients benefited from using the DIBH technique
with respect to reduced cardiopulmonary doses.
Our study confirms the results of previous studies.
Stanzl et al. found in a dose plan study including 11
patients, a similar reduction in mean dose to the
entire heart from 4 Gy to 2.5 Gy using DIBH [3].
The lower dose reported in that study might be due
to a smaller CTV which only included the breast and
the IMC lymph nodes. However, Stranzl et al. did not
report anything about the dose coverage to PTV,
which is essential when OAR doses are to be com-
pared. Pedersen et al. also found a reduction in car-
diopulmonary doses using DIBH for seven patients
with left-sided breast tumors where IMC and supra-
clavicular lymph nodes were included in the PTV [4].
Median heart volume receiving ⬎50% of the pre-
scribed CTV dose was reduced from 8% using FB to
1% using DIBH, and the median ipsilateral relative
lung volume receiving ⬎50% of the prescribed dose
was reduced from 37% for FB to 31% for DIBH. The
reduction in median V25Gy for ipsilateral lung was
similar in our study (42.8% for FB vs. 30.4% for
DIBH), while the reduction in median V25Gy for the
heart was larger (4.5% for FB vs. 0.1% for DIBH).
The increased reduction in median V25Gy for the
heart might be due to the larger DIBH amplitude in
our study. The median V25Gy to ipsilateral lung was
not decreased in our study as compared to the study
by Pedersen et al., even though the DIBH amplitude
was larger. This might be due to better PTV coverage
in our study and the use of different gantry angles.
A preliminary analysis of updated EBCTCG data
has related mortality from heart disease to estimated
cardiac doses in over 30 000 female breast cancer
patients followed for up to 20 years. There is clear
evidence that the radiation-related increase in mor-
tality is higher in trials with larger mean cardiac RT
doses and that the risk of death from heart disease
increases by 3% per Gy [17]. Several other studies
have also shown that radiation related heart disease
can occur following doses below 20 Gy, which
emphasize the importance of reducing the mean dose
to the heart [17]. Even a mean heart dose of about
4 Gy has been related to development of coronary
heart disease [17]. The LAD coronary artery which
supplies a significant volume of the heart is particu-
larly vulnerable when the breast or chest wall is
treated by tangential fields [18]. This demonstrates
the importance of developing techniques that reduce
the radiation dose to heart and LAD coronary artery.
In our study, the mean dose to the heart was reduced
with 50% and mean dose as well as D2% to LAD
coronary artery were reduced with 56.4% and 38.5%,
respectively, using the DIBH technique.
Pulmonary complications may also be induced
by RT for breast cancer patients, and radiation
pneumonitis is one of the most common clinical tox-
icities in these patients [19]. The risk of symptomatic
pneumonitis requiring treatment may increase to
4% in patient with regional node irradiation, com-
pared to about 1% when irradiation is confined to
the breast [18]. The first results from the EORTC
trial 22922/10925 show that the lung toxicity (fibro-
sis; dyspnoea; pneumonitis; any lung toxicities) at
three years in stage I to III breast cancer was sig-
nificantly increased with internal mammary and
medial supraclavicular lymph node irradiation (4.3%
vs. 1.3%) [20]. Various Vx of ipsilateral lung i.e.
V5Gy, V13Gy, V20Gy, V25Gy and V30Gy, are asso-
ciated with radiation pneumonitis risk, which sug-
gests that there is no sharp dose threshold below
which there is no risk [19]. In our study a reduction
in DVH parameters for total as well as ipsilateral
lung was observed with DIBH. Considering the
 Heart and lung doses with DIBH for breast cancer patients
national guidelines, a cut-off value of ipsilateral lung
V20Gy ⫽ 35%, all 17 patients exceeded this limit
with FB compared to only six patients using DIBH.
Average mean total lung dose was reduced from
10.3 Gy with FB to 8.1 Gy with DIBH, correspond-
ing to a risk of radiation pneumonitis of 7.1% and
5.5%, respectively [19]. The risk is considered low
in both cases. The average MLD was increased in
DIBH plans as compared to FB plans, suggesting an
increased risk for pulmonary complications. How-
ever, MLD may not be used as an indicator of pul-
monary complications using the DIBH technique,
since the relative irradiated lung volume during
DIBH is much smaller than during FB.
Mean dose to the contralateral breast increased
slightly (0.5 Gy) with DIBH. This result is similar
to the one seen by Stanzl et al., who found a non-
significant increase in mean dose to contralateral
breast from 1.2 Gy with FB to 1.4 Gy with DIBH
[3]. The increase is probably of no clinical relevance.
In a recent study using the same dataset as in the
present study where the treatment was planned for
left breast only, no significant difference was found
in normal tissue complication probability (NTCP)
for contralateral breast using either the DIBH or the
FB technique [21]. In this study the AAA was used
for dose calculation.
The DIBH technique led to a considerable reduc-
tion in both mean dose and average dose maximum
(D2%) to the heart. This is an advantage over IMRT,
VMAT and tomotherapy, which in several studies
have been shown only to reduce the maximum dose,
while increasing the mean dose. Goddu et al. and
Fogliata et al. found an increase in mean heart dose
with tomotherapy for left-sided breast cancer with
lymph nodes in the axilla, supraclavicular region and
internal mammary region included in the target vol-
ume [22,23]. Goddu et al. found a mean heart dose
of 12.2 ⫾ 1.8 Gy, and Fogliate et al. found a mean
heart dose in the range 8.7–21.1 Gy. Lohr et al.
found a 24% increase in mean dose to the heart
(from 6.85 Gy to 8.52 Gy) using IMRT of left-sided
breast cancer (no lymph nodes included in the
target) compared to conventional tangential fields
[24]. The increase is primarily caused by the increase
in the low-dose volume. In our study mean heart
dose was 3.1 ⫾ 1.9 Gy using the DIBH technique.
Remouchamps et al. found that radiation during
moderate DIBH (using the ABC system from Elekta
AB, Sweden) played a larger role in improving the
quality of loco-regional breast irradiation including
the IMC lymph nodes, than IMRT alone [5]. They
found that mean heart V30Gy was reduced from
16.3% with IMRT alone to 3.1% with IMRT in
combination with DIBH, thus reducing the absolute
mean heart NTCP by 5%. In our study mean heart
343
V25Gy was reduced from 6.7% using FB to 1.2%
using DIBH, which might indicate that DIBH alone
is recommended for breast irradiation.
In our experience, respiratory gating with the
DIBH technique and audiovisual guidance for breast
cancer patients is a relatively simple technique to
implement in clinical practice [6]. All patients
referred for left-sided loco-regional RT are treated
with respiratory gating, regardless of age. Patients
who receive tangential treatment to the breast only
are offered gated RT if they are 60 years or younger.
These choices are based on the fact that loco-regional
irradiation often results in higher radiation exposure
to both the heart and the ipsilateral lung as compared
to tangential irradiation only. We only acquired one
CT-scan during DIBH. The degree of patient com-
pliance is high. About 1% of the patients have not
been able to follow the audio-visual instructions that
are necessary for gated RT. This has either been very
old and frail patients, patients with a psychiatric
disease or mental retardation. The total treatment
time per patient at the accelerator is approximately
the same as without respiratory gating, and the scan
time at the CT is also equal to a CT-scan during FB.
The patients need about 20 min to rehearse the
DIBH technique. However, the planning procedure
itself is usually easier to perform as compared to a
non-gated procedure, thus in summary no extra
time needs to be calculated for a DIBH plan. The
dosimetry is, apart from the effect of decreased lung
density, equivalent to conventional RT.
This study shows that respiratory gating during
DIBH is a suitable technique for loco-regional breast
irradiation even when IMC lymph nodes are included
in the PTV. For all patients the cardiopulmonary doses
are considerably decreased for all dose levels without
compromising the dose coverage to PTV, which is an
advantage over IMRT, VMAT and tomotherapy.
Acknowledgements
We thank the Norwegian Cancer Society for the
financial support given towards this study.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are respon-
sible for the content and writing of the paper.
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