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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 intensity modulated RT (IMRT), volumetric modu-
cancer represents a treatment planning challenge, lated arc therapy (VMAT), tomotherapy and respira-
especially when the internal mammary chain (IMC) tory gating have been introduced as possible treatment
lymph nodes are included in the target volume. Due strategies to reduce the cardiopulmonary doses.
to the increased radiation dose, especially to the Several authors [3–5] have shown that respiratory
heart, the IMC lymph nodes are often excluded from gating reduces the cardiopulmonary doses when irra-
the target volume. However, recent studies indicate diating during deep inspiration. Deep inspiration
increased survival after radiation of IMC lymph increases the distance between the breast and the
nodes among patients with lymphatic draining to the heart due to increased lung volume, and the heart is
IMC lymph nodes [1,2]. Together with the extended partially or completely moved out of the high dose
use of cardiotoxic systemic therapy this highlights the region. The relative volume of the ipsilateral lung
need for improvements in RT delivery to reduce irra- exposed to irradiation is also decreased. In a recent
diation to organs at risk (OAR) and normal tissue. treatment planning study we were able to show that
In recent years different RT techniques, such as 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 axilla, supraclavicular region and the IMC of the left
tangential treatment of left-sided breast cancer side were defined as the target in all patients. The
patients with considerably reduced cardiac doses median age was 60 (range: 29–70) years. The patients
without compromising target coverage [6]. had to be able to cooperate and to hold their breath
The purpose of this treatment planning study was for 15–20 s. The study was approved by the regional
to carefully evaluate the dose to OAR for patients ethical committee as a project for quality assurance
with left-sided breast cancer when irradiating the in health care. The CT series were taken prior to the
breast and loco-regional lymph nodes in the axilla, clinical implementation of the DIBH technique, and
supraclavicular region and IMC during free breath- with one exception, the patients were not treated
ing (FB) and DIBH, respectively. The inclusion of with respiratory gating.
axillary levels, supraclavicular region and the IMC
was done for scientific purposes only in order to test CT scanning
our DIBH technique in a “worst case” scenario. To
Two CT series were obtained for each patient, one
our knowledge, this is the first study with a reason-
during FB and the other during DIBH. The patients
able number of patients that documents good and
were placed in a supine position with bilateral arm
similar dose coverage to the planning target volume
abduction above the head using a PosiboardTM-2
(PTV) for both techniques to be compared. Equal
breast board (CIVCO Medical Solutions, Kalona,
PTV dose coverage is important when comparing the
IA, USA). In our department all breast cancer
dose to OAR. In contrast to others who have used
patients undergoing RT are placed in this treatment
the DIBH technique, we gave our patients audio-
position, independent of laterality and lymph node
visual guidance to reach the same amplitude level
involvement. CT-scans were performed at 3 mm
at each deep breath, and to maintain very stable
intervals and encompassed both breast and the whole
amplitude within each breath-hold.
thoracic cavity including the heart and both lungs.
The image acquisition was in helical mode.
Patients and methods The Varian RPMTM respiratory gating system,
version 1.6 (Varian Medical Systems, Palo Alto, CA,
Patient population
USA) was used for real time registration of the respira-
Computed tomography (CT) series of 17 patients tion. An infrared reflecting marker was placed on the
who were referred for adjuvant RT after breast con- patient, normally over the xiphoid process, and a video
serving surgery at Stavanger University Hospital camera registered the anteroposterior motion of the
between January and October 2006 were analyzed. marker due to respiration. The amplitude of DIBH, i.e.
The inclusion of patients was not consecutive, but the chest wall motion was individually set prior to the
based on logistics availability (staff and venues). CT-scan. The DIBH amplitude was only allowed to
Twelve of these patients had left-sided and five had deviate ⫾ 1 mm during the scanning. Figure 1 shows a
right-sided breast cancer, but for study purposes the typical DIBH breathing curve. The patient received
mammary glandular tissue and lymph nodes in the visual guidance through the binocular head mounted

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.
Heart and lung doses with DIBH for breast cancer patients 335
display to sustain reproducibility and stability of the Treatment planning
DIBH amplitude. The scanning time was typically
An individually optimized mono-isocentric photon
around 20 s and most patients managed to complete
field treatment plan was obtained for each CT
the scan during one DIBH. For those who did not, the
series. The technique included wide opposing
CT had to be manually stopped, and restarted during
6 MV tangential fields covering the remaining
the next DIBH. In this study the mean anteroposterior
breast and internal mammary nodes and AP-PA
(AP) chest wall movement at the position of the xiphoid
fields, 6 MV and 15 MV, respectively, covering
process was 3 mm (range: 1.6–5.0 mm) during FB.
the axillary and supraclaviculary nodes, abutting
With the DIBH technique the chest wall was moving
each other half-beam. Occasionally low weighted
an average of 18 mm (range: 14.6–27.0 mm) in the
15 MV fields, with the same geometry as the 6 MV
anterior direction when the patients breathed in deeply,
tangential fields, were added. All fields were con-
and during breath hold the AP chest wall movement
formal with multileaf collimators and wedges in
was only allowed to vary 2 mm.
some cases. The isocenter was individually deter-
mined, but was equally positioned inside the CTV
Delineation of target and OAR in the transition between mammary tissue and
supraclavicular lymph nodes in both CT series, FB
The CT series were transferred to an Eclipse 3-D and DIBH, for the same patient.
treatment planning workstation, version 8.0 (Varian
Medical Systems) and the clinical target volume The following dose constraints were given:
(CTV) and OAR were delineated.
The mammary glandular tissue and lymph nodes 1) Minimum 98% of the PTV should be covered
in the axilla, supraclavicular region and in the IMC by the 95% isodose line (V95% ⱖ98%).
of the left side were defined as CTV. The internal 2) The 95% isodose line should cover the dorsal
mammary nodes located in intercostal space 1 to 3 limit of the PTV (by visual inspection).
and nodes of level I, II and III of the axilla were 3) The mean dose to PTV should be close to 100%
completely included in the CTV. of the prescribed dose, and not above 102%.
The heart, the left anterior descending (LAD) 4) Dose maximum should not exceed 110% and
coronary artery, both lungs and the contralateral preferably not 107%.
breast were considered OAR. The lung volume was 5) The dose to OAR should be kept as low as pos-
automatically generated using the auto-contouring sible, without compromising the PTV dose, i.e.
tool of the treatment planning system. The heart the criteria of PTV coverage should be fulfilled,
volume was defined as the entire visible myocardium, even if the national guidelines for doses to OAR
including the pericardium, from apex of the heart, to were exceeded.
the right auricle, atrium, and infundibulum of the For each patient only minor difference between
ventricle. The ascending aorta, the pulmonary trunk the two plans, FB and DIBH, with respect to target
and the superior vena cava were excluded. The LAD dose coverage, dose conformity, maximum dose,
coronary artery was delineated in the anterior inter- beam energy and geometry, should be accepted.
ventricular groove to the apex of the heart. The con- In a clinical setting the prescribed dose to PTV
tralateral breast was defined as all glandular breast is 46 Gy in 2 Gy fractions followed by 4 Gy in 2 Gy
tissue of the right side. fractions to the left breast only. For simplicity, in
For consistency, the delineation of CTV and the this study the prescription dose was 50 Gy in 2 Gy
contralateral breast was performed by the same oncol- fractions to PTV. The dose to heart and ipsilateral
ogist for all patients. The LAD coronary artery and lung is therefore slightly increased, about 0.5%, as
the heart were delineated by a radiation technologist. compared to the clinical setting.
Delineation of the LAD coronary artery was done
under supervision from a cardiologist, and the delin- National guidelines recommend the following dose
eation of the heart was verified by the oncologist. limitation to OAR:
The margin from CTV to PTV was 5 mm, except 1) The volume of the heart receiving a dose of
for superficial areas where PTV was never closer than 25 Gy or more should be smaller than 5%
5 mm to the skin. The margins were the same for (V25Gy ⱕ 5%).
DIBH and FB. Due to the chosen 2 mm gating win- 2) The volume of ipsilateral lung receiving a dose
dow the movement of the chest wall during the of 20 Gy or more should be smaller than 35%
DIBH plateau was the same, or smaller, as compared (V20Gy ⱕ 35%).
to FB. Hence the margin to compensate for CTV
motion did not have to be increased with the DIBH The guidelines do not have specific recommenda-
technique. OAR were delineated without margins. tions regarding the dose to contralateral breast and
336 M. H. B. Hjelstuen et al.
LAD coronary artery, except keeping them as low as CIHealthy Tissues ⫽ (V95%/TV95%)
possible.
where TV95% is the volume of the 95% isodose. This
The calculation algorithm used was Eclipse pen-
equation defines volume of healthy tissue receiving a
cil beam (PB) described by Storchi et al. [7] with the
dose greater than or equal to 95% of the prescribed
modified Batho inhomogeneity correction [8]. All
dose. The CIHealthy Tissues ranges from 0 to 1, where 1
plans were made by the same physicist.
is the ideal value (perfect conformation).
The distance from isocenter to the cranial limit of
Outcome measures and statistical analysis CTV was obtained from the CT series, by counting
the number of CT slices from isocenter to the last
For each patient cumulative dose-volume histograms
cranial slice with CTV delineation, and multiply by
(DVHs) were calculated for all delineated volumes
the slice thickness of 3 mm. Similarly, the distances
in the two different treatment plans. Dose to PTV
from isocenter to the cranial limit of the lung and the
and OAR was assessed. The volumes, mean and
mammary tissue of the left side as well as the caudal
maximum doses were obtained from the DVH
limit of CTV in the IMC region were obtained.
statistics. The relative volume Vx, irradiated to a
Paired Wilcoxon test was used for statistical
minimum dose x (in Gy or %), e.g. V25Gy for the
analysis of the differences with computer software
heart, V20Gy for the ipsilateral lung and V95% for
SPSS version 16.0. Data were considered statistically
PTV, were obtained from the DVH graphs. The
significant for p ⬍ 0.05.
relative dose Dx%, covering minimum x% of the
volume of interest, e.g. D2%, D50% and D98% were
Results
also obtained from the DVH graphs. The maximum
heart distance (MHD) and maximum lung distance PTV and OAR volumes
(MLD) were measured in beams eye view.
The homogeneity and conformity indices were Table I shows the mean volume of PTV and OAR
calculated. The homogeneity index (HI) for PTV is during FB and DIBH for all 17 patients. Com-
defined as follows [9]: pared to FB, the mean volume of ipsilateral
lung increased about two-fold during DIBH
HI ⫽ (D2%–D98%)/D50% (1178.2 cm3 vs. 2165.1 cm3, p ⬍ 0.001), while the
An HI of zero indicates that the dose distribution is mean heart volume decreased about 10% in size
almost homogeneous. (616.5 cm3 vs. 559.8 cm3, p ⫽ 0.003). For the
The target conformity index (CI) as well as the other delineated volumes no significant difference
healthy tissues conformity index (CIHealthy Tissues) in size was found.
were calculated. The CI is defined as follows [10]: Figure 2 shows the CTV, the mammary tissue
and the ipsilateral lung for the same patient during
CI ⫽ (V95%/VPTV) FB and DIBH. The position of the isocenter inside
where V95% is the volume of PTV covered by the the CTV was identical for the two CT series, 1.24
95% isodose line, and VPTV is the volume of PTV. cm caudally to the cranial border of the mammary
This equation defines the quality of the coverage of tissue. As shown in Figure 2 the shape and position
the target. The index ranges from 0 to 1, where 1 of CTV was somewhat changed during DIBH com-
indicates that all of the target volume is covered by pared to FB. The CTV was moved cranially during
the prescribed dose. DIBH with the isocenter position (mean: 0.82 cm)
The healthy tissues conformity index is defined closer to the apex of the lung. During DIBH the
as follows [10], when the reference isodose is set length of the supraclavicular region was reduced with
equal to the 95% isodose: 1.12 cm (mean value, p ⬍ 0.001) whereas the length

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 DIBH p-value

PTV 1362.8 ⫾ 374.7 [843.4–2105.9] 1346.4 ⫾ 365.0 [879.4–2074.0] 0.163


Heart 616.5 ⫾ 75.5 [460.7–750.7] 559.8 ⫾ 72.2 [458.1–676.0] 0.003*
LAD coronary artery 1.0 ⫾ 0.6 [0.2–2.5] 1.0 ⫾ 0.4 [0.6–1.8] 0.253
Ipsilateral lung 1178.2 ⫾ 343.2 [630.0–1978.6] 2165.1 ⫾ 509.9 [1229.3–3249.7] ⬍ 0.001*
Total lung 2635.2 ⫾ 693.4 [1482.3–4246.6] 4676.3 ⫾ 1010.9 [2634.7–6763.8] ⬍ 0.001*
Contralateral breast 631.5 ⫾ 295.2 [252.9–1282.4] 627.4 ⫾ 303.3 [250.1–1298.1] 0.301

LAD, left anterior descending.


*Significantdifference (p ⬍ 0.05) between FB and DIBH.
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 The mean DVHs for FB and DIBH, averaged for all
medial tangential field for both plans for the same 17 patients, for the OAR, are shown in Figure 4. The
patient are shown in Figure 3. The figure shows that mean DVHs show that the low-, medium- as well as
the lungs greatly increase in volume during deep inspi- the high dose region in the heart, the LAD coronary
ration, separating the heart from the chest wall. In artery and the ipsilateral lung were reduced with
addition, the heart moves caudally as the lungs push DIBH. For the contralateral breast the mean DVHs
the diaphragm downward. Thus, the heart is moved indicate that the volumes of low and medium doses
out of the beam portals and the high dose region. were slightly increased with the DIBH technique.
The mean DVHs for FB and DIBH, averaged for The OAR treatment planning results are listed in
all 17 patients, for PTV are shown in Figure 4. The Table II.
DVHs for PTV were quite similar in DIBH and FB
plans reflecting a similar and homogeneous PTV
Cardiac doses
coverage. The treatment planning results are sum-
marized in Table II. All plans fulfilled the criterion of All treatment plans based on FB technique included
dose coverage to the PTV as described in methods. heart tissue within the beam portals (Table II).
There was no difference in average mean dose, D98% With the DIBH technique the heart was completely
and V95% for PTV in FB and DIBH, whereas aver- outside the beam portals for seven of the 17 patients
age D2% was slightly higher in the DIBH plans (53.2 (41.2%). The average MHD decreased from 1.9 cm
Gy vs. 53.0 Gy in FB plans, p ⫽ 0.006). (range 0.9–3.7 cm) using FB to 0.7 cm (range 0.0–
No statistical differences were seen in mean HI 3.4 cm) using DIBH. The average mean heart dose
and mean target CI in FB and DIBH plans. The was reduced from 6.2 Gy (range 2.5–14.4 Gy) to 3.1
CIHealthy Tissue, however, were significantly lower in 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). from 23.0 Gy (range 3.7–48.2 Gy) to 10.9 Gy (range
The mean V25Gy was significantly decreased in the 3.1–38.9 Gy). Mean V25Gy for the LAD coronary
DIBH plans (1.2% vs.6.7% with FB, p ⬍ 0.001). artery was also significantly reduced, from 48.4%
Scatter plot of V25Gy in FB and DIBH plans for with FB to 14.1% with DIBH (p ⫽ 0.001). Average
each patient are shown in Figure 5. V25Gy was larger D2% for the LAD coronary artery was reduced
than 5% in eight patients (47.1%) using the FB tech- (p ⬍ 0.001) from 39.2 Gy (range 5.1–50.1 Gy) to
nique, compared to only one patient (5.9%) when 24.1 Gy (range 4.0–47.8 Gy).
using DIBH (Figure 5). The largest V25Gy value
observed was 23.0% for FB and 11.5% for DIBH.
Pulmonary doses
These values were not from the same patient. The
patient with the largest V25Gy value (23%) during Average mean dose to the ipsilateral lung was 5.3
FB achieved a V25Gy of 2.2% with the DIBH tech- Gy lower with DIBH than with FB (16.4 Gy vs.
nique. Average D2% for the heart was reduced from 21.7 Gy, p ⬍ 0.001). Similarly, the average V20Gy
34.1 Gy in FB plans to 13.1 Gy in DIBH plans for ipsilateral lung was significantly reduced from
(p ⬍ 0.001). 44.5% (range 35.8–51.2%) using FB to 32.7%
For the LAD coronary artery there was a signifi- (range 24.5–41.8%) using DIBH (Table II). V20Gy
cant (p ⬍ 0.001) reduction in average mean dose 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 10.3 Gy (range 8.4–12.1 Gy) with FB to 8.1 Gy
than 35% with FB, whereas this was true only for (range 6.5–10.7 Gy) with DIBH (p ⬍ 0.001).
six of the 17 patients with DIBH (Figure 6). In FB,
13 patients had V20Gy ⬎ 41.8% which was the
Contralateral breast
largest V20Gy value observed in DIBH plans.
The average MLD of the medial field increased Average mean dose to the contralateral breast was 0.5
from 4.7 cm with FB to 5.1 cm with DIBH Gy higher in DIBH plans than in FB plans (2.7 Gy vs.
(p ⫽ 0.017). Average mean dose to total lung 2.2 Gy, p ⫽ 0.012), and V2Gy was 3.9% larger (26.1%
volume was reduced with 2.2 Gy using DIBH, from 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 Including the IMC lymph nodes in the CTV is
plans (16.5 Gy vs. 13.2 Gy with FB, p ⫽ 0.047). debated, due to conflicting results in outcome gain
and increased risk of cardiac mortality. However,
the results of the Early Breast Cancer Trialists’ Col-
Discussion
laborative Group (EBCTCG) meta-analysis dem-
In this CT planning study we were able to demon- onstrate the importance of local treatment on
strate that irradiation of the left breast and regional long-term survival, and the fact that IMC lymph
lymph nodes, including the IMC, in a DIBH tech- node treatment was included in 24 of 25 post-mas-
nique utilizing audio-visual guidance, leads to a sub- tectomy RT studies included in the meta-analysis
stantial reduction in cardiopulmonary doses without have led to renewed interest in IMC lymph node
compromising target coverage. treatment of breast cancer [1]. Lymphoscintigraphy
Heart and lung doses with DIBH for breast cancer patients 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
Figure 5. Volume of heart (in %) receiving 25 Gy or more during DIBH. Thus, the cardiopulmonary dose
(V25Gy) in FB plans versus DIBH plans plotted for each patient reduction observed during DIBH is mostly caused
individually. DIBH, deep inspiration breath-hold; FB, free by the movement of the heart out of the high dose
breathing.
region and the increased lung volume.
studies have shown that about one of 25 breast can- The treatment planning was done with focus on
cer patients have IMC lymph node metastases [11], similar and good PTV coverage (V95% ⬎ 98%) for
and that medial tumors are more likely than lateral both breathing techniques. Good PTV coverage is a
tumors to drain to the IMC lymph nodes [1,12]. goal in RT, but not always achievable in clinical prac-
The incidence of lymph node metastases of the tice, where compromising target dose against OAR
internal mammary and medial supraclavicular is a common challenge. Our study shows the cardio-
lymph node chain are reported to be in the range pulmonary doses as they would be, with optimal tar-
4–9% in axillary node negative patients and get coverage without compromises.
16–52% for axillary node positive patients [2,13]. The FB and DIBH plans in our study showed
Studies on large series of breast cancer patients equal and good PTV coverage as measured by V95%
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
Figure 6. Volume of ipsilateral lung (in %) receiving 20 Gy or
tangential fields were necessary to cover the internal more (V20Gy) in FB plans versus DIBH plans plotted for each
mammary nodes, but increased the volume of heart, patient individually. DIBH, deep inspiration breath-hold; FB, free
ipsilateral lung and contralateral breast included in breathing.
342 M. H. B. Hjelstuen et al.
and D98% as well as with HI and CI indices. All lung volume receiving ⬎50% of the prescribed dose
plans fulfilled the strict planning criterion of was reduced from 37% for FB to 31% for DIBH. The
V95% ⬎ 98%, and the 95%-isodose was by visual reduction in median V25Gy for ipsilateral lung was
inspection ensured to cover the dorsal part of PTV similar in our study (42.8% for FB vs. 30.4% for
including the internal mammary nodes with margins. DIBH), while the reduction in median V25Gy for the
It should be noted that the PB algorithm overesti- heart was larger (4.5% for FB vs. 0.1% for DIBH).
mates the target dose as discussed by Vikström et al. The increased reduction in median V25Gy for the
[6]. In clinical practice it is recommended to use a heart might be due to the larger DIBH amplitude in
modern calculation algorithm with inhomogeneity our study. The median V25Gy to ipsilateral lung was
corrections that also account for lateral electron scat- not decreased in our study as compared to the study
ter, i.e. the analytical anisotropic algorithm (AAA) or by Pedersen et al., even though the DIBH amplitude
the collapsed cone (CC) algorithm. However, as was larger. This might be due to better PTV coverage
most previous studies used the same algorithm, if in our study and the use of different gantry angles.
stated, the comparison of doses is relevant. Both A preliminary analysis of updated EBCTCG data
plans had a CIHealthy tissue larger than 0.6, and can be has related mortality from heart disease to estimated
considered to be conformal according to Lomax and cardiac doses in over 30 000 female breast cancer
Scheib [16], who defined irradiation to be conformal patients followed for up to 20 years. There is clear
if the CIHealthy tissue index was ⱖ0.6. However, the evidence that the radiation-related increase in mor-
DIBH plans had a slightly decreased normal tissue tality is higher in trials with larger mean cardiac RT
conformity compared to FB plans, due to a 50 cm3 doses and that the risk of death from heart disease
larger TV95%. The increased TV95% as well as the increases by 3% per Gy [17]. Several other studies
slightly increased average D2% in the DIBH plans have also shown that radiation related heart disease
might be due to the increased photon beam trans- can occur following doses below 20 Gy, which
mission caused by decreased lung density during emphasize the importance of reducing the mean dose
DIBH. The difference in the CI between the FB and to the heart [17]. Even a mean heart dose of about
DIBH plans is expected to be larger when the AAA 4 Gy has been related to development of coronary
or CC algorithm is used. heart disease [17]. The LAD coronary artery which
The DVHs in Figure 4 demonstrate the great supplies a significant volume of the heart is particu-
benefit of the DIBH technique with respect to car- larly vulnerable when the breast or chest wall is
diopulmonary doses. The volume of heart and lungs treated by tangential fields [18]. This demonstrates
irradiated to high-, medium- and low-dose levels the importance of developing techniques that reduce
were considerably reduced with the DIBH technique. the radiation dose to heart and LAD coronary artery.
Eleven patients fulfilled the national guidelines with In our study, the mean dose to the heart was reduced
respect to pulmonary doses using the DIBH tech- with 50% and mean dose as well as D2% to LAD
nique without compromising the PTV coverage, coronary artery were reduced with 56.4% and 38.5%,
whereas no patients did using the FB technique. respectively, using the DIBH technique.
Average mean heart dose was halved and only one Pulmonary complications may also be induced
patient had V25Gy ⬎5% with DIBH. However, all by RT for breast cancer patients, and radiation
patients benefited from using the DIBH technique pneumonitis is one of the most common clinical tox-
with respect to reduced cardiopulmonary doses. icities in these patients [19]. The risk of symptomatic
Our study confirms the results of previous studies. pneumonitis requiring treatment may increase to
Stanzl et al. found in a dose plan study including 11 4% in patient with regional node irradiation, com-
patients, a similar reduction in mean dose to the pared to about 1% when irradiation is confined to
entire heart from 4 Gy to 2.5 Gy using DIBH [3]. the breast [18]. The first results from the EORTC
The lower dose reported in that study might be due trial 22922/10925 show that the lung toxicity (fibro-
to a smaller CTV which only included the breast and sis; dyspnoea; pneumonitis; any lung toxicities) at
the IMC lymph nodes. However, Stranzl et al. did not three years in stage I to III breast cancer was sig-
report anything about the dose coverage to PTV, nificantly increased with internal mammary and
which is essential when OAR doses are to be com- medial supraclavicular lymph node irradiation (4.3%
pared. Pedersen et al. also found a reduction in car- vs. 1.3%) [20]. Various Vx of ipsilateral lung i.e.
diopulmonary doses using DIBH for seven patients V5Gy, V13Gy, V20Gy, V25Gy and V30Gy, are asso-
with left-sided breast tumors where IMC and supra- ciated with radiation pneumonitis risk, which sug-
clavicular lymph nodes were included in the PTV [4]. gests that there is no sharp dose threshold below
Median heart volume receiving ⬎50% of the pre- which there is no risk [19]. In our study a reduction
scribed CTV dose was reduced from 8% using FB to in DVH parameters for total as well as ipsilateral
1% using DIBH, and the median ipsilateral relative lung was observed with DIBH. Considering the
Heart and lung doses with DIBH for breast cancer patients 343
national guidelines, a cut-off value of ipsilateral lung V25Gy was reduced from 6.7% using FB to 1.2%
V20Gy ⫽ 35%, all 17 patients exceeded this limit using DIBH, which might indicate that DIBH alone
with FB compared to only six patients using DIBH. is recommended for breast irradiation.
Average mean total lung dose was reduced from In our experience, respiratory gating with the
10.3 Gy with FB to 8.1 Gy with DIBH, correspond- DIBH technique and audiovisual guidance for breast
ing to a risk of radiation pneumonitis of 7.1% and cancer patients is a relatively simple technique to
5.5%, respectively [19]. The risk is considered low implement in clinical practice [6]. All patients
in both cases. The average MLD was increased in referred for left-sided loco-regional RT are treated
DIBH plans as compared to FB plans, suggesting an with respiratory gating, regardless of age. Patients
increased risk for pulmonary complications. How- who receive tangential treatment to the breast only
ever, MLD may not be used as an indicator of pul- are offered gated RT if they are 60 years or younger.
monary complications using the DIBH technique, These choices are based on the fact that loco-regional
since the relative irradiated lung volume during irradiation often results in higher radiation exposure
DIBH is much smaller than during FB. to both the heart and the ipsilateral lung as compared
Mean dose to the contralateral breast increased to tangential irradiation only. We only acquired one
slightly (0.5 Gy) with DIBH. This result is similar CT-scan during DIBH. The degree of patient com-
to the one seen by Stanzl et al., who found a non- pliance is high. About 1% of the patients have not
significant increase in mean dose to contralateral been able to follow the audio-visual instructions that
breast from 1.2 Gy with FB to 1.4 Gy with DIBH are necessary for gated RT. This has either been very
[3]. The increase is probably of no clinical relevance. old and frail patients, patients with a psychiatric
In a recent study using the same dataset as in the disease or mental retardation. The total treatment
present study where the treatment was planned for time per patient at the accelerator is approximately
left breast only, no significant difference was found the same as without respiratory gating, and the scan
in normal tissue complication probability (NTCP) time at the CT is also equal to a CT-scan during FB.
for contralateral breast using either the DIBH or the The patients need about 20 min to rehearse the
FB technique [21]. In this study the AAA was used DIBH technique. However, the planning procedure
for dose calculation. itself is usually easier to perform as compared to a
The DIBH technique led to a considerable reduc- non-gated procedure, thus in summary no extra
tion in both mean dose and average dose maximum time needs to be calculated for a DIBH plan. The
(D2%) to the heart. This is an advantage over IMRT, dosimetry is, apart from the effect of decreased lung
VMAT and tomotherapy, which in several studies density, equivalent to conventional RT.
have been shown only to reduce the maximum dose, This study shows that respiratory gating during
while increasing the mean dose. Goddu et al. and DIBH is a suitable technique for loco-regional breast
Fogliata et al. found an increase in mean heart dose irradiation even when IMC lymph nodes are included
with tomotherapy for left-sided breast cancer with in the PTV. For all patients the cardiopulmonary doses
lymph nodes in the axilla, supraclavicular region and are considerably decreased for all dose levels without
internal mammary region included in the target vol- compromising the dose coverage to PTV, which is an
ume [22,23]. Goddu et al. found a mean heart dose advantage over IMRT, VMAT and tomotherapy.
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 Acknowledgements
(from 6.85 Gy to 8.52 Gy) using IMRT of left-sided We thank the Norwegian Cancer Society for the
breast cancer (no lymph nodes included in the financial support given towards this study.
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 Declaration of interest: The authors report no
dose was 3.1 ⫾ 1.9 Gy using the DIBH technique. conflicts of interest. The authors alone are respon-
Remouchamps et al. found that radiation during sible for the content and writing of the paper.
moderate DIBH (using the ABC system from Elekta
AB, Sweden) played a larger role in improving the References
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