Global Journal of Breast Cancer Research, 2015, 3, 27-32
27
Breast Sub-Volumes: Preliminary Results of a New Concept to
Gradually decrease the Dose from the Tumor Bed to the Peripheral
Breast Using Simplified IMRT
Silvia Beatriz Zunino*
Obispo Oro 423, Cordoba, 5000, Argentina
Abstract: Purpose: To gradually decrease the dose from the tumor bed to the peripheral breast volume.
Methods and Materials: The whole breasts (small, medium and large) of 31 patients were divided into three subvolumes: CTV_SIB (CTV of the simultaneous integrated boost); CTV_proximal, 3 cm expansion from the CTV_SIB
across the CTV_ breast; and CTV_distal. Simplified intensity-modulated radiation technique (sIMRT) was used.
Radiation therapy was delivered in 25 fractions over 5 weeks. The dose prescribed to the PTV_SIB ranged from 62, 5
Gy to 66 Gy, 50 Gy and 46 Gy to the PTV_proximal and PTV_distal respectively. The dose volume histograms (DVHs)
and the dose distribution of D95% were analyzed and compared for each sub-volume. The dose-volume constraints
used for the lung and the heart were V20 Gy <10%, and V10 Gy <10% respectively.
Results: Between May 16 and July 27, 2013, thirty-one consecutive early breast cancer patients referred for radiation
therapy were planned in order to decrease the dose delivered to the breast volume.
The D95% for PTV_SIB, PTV_proximal and PTV_distal were 62.6 Gy (60.5-65.6 Gy); 49,3 Gy (47.0-51.1 Gy) and 45.5
Gy (43.2-47.3 Gy) respectively (p=0.0000).
The 21 left breast plans showed no statistical significant difference in the dose received by the heart and the left lung
between the conventional technique and the 3-sub-volume technique. The median dose received by the heart was 1.2
Gy lower with the 3 sub-volume technique compared with the conventional technique.
Conclusion: The three breast sub-volumes irradiated with simplified intensity-modulated technique would allow for a
slight but significant gradual decrease of the dose from the tumor bed to the distal breast. A long-term follow-up is
required to confirm whether this dose decrease may contribute to reduce toxicities.
Keywords: Breast, sub-volume, gradual dose decrease, radiotherapy, simplified intensity modulated technique.
1. INTRODUCTION
The rationale behind adjuvant post-operative
radiotherapy (RT) following breast conserving surgery
(BCS) is to obtain the reduction of local recurrence
rates and improve survival. This beneficial effect has
been demonstrated in several randomized studies and
meta-analyses [1-4].
The widespread adoption of BCS and adjuvant
post-op radiation therapy, especially in women with
early stage breast cancer, increases the importance of
late complications due to the long expected diseasefree survival [5].
Several published meta-analyses confirm that
adjuvant radiation therapy improves survival in breast
cancer patients; however, this benefit is offset by an
increase in non-breast cancer mortality [6,7].
Furthermore, in a systematic review Mukesh
Mukesh et al. [8] evaluate the evidence for a
relationship between the volume of breast tissue
*Address correspondence to this author at the Obispo Oro 423, Cordoba,
5000, Argentina: Tel: +54-351-4424600; Fax: +54-351-4691459;
E-mail: [email protected]
E-ISSN: 2309-4419/15
irradiated and the late normal tissue complications
(NTCs) including overall cosmesis, breast fibrosis,
breast induration and telangiectasia. The authors
hypothesize that a modest dose reduction to part of the
breast would diminish NTCs.
The aim of the present study is to show the
preliminary dosimetric results of gradual dose reduction
from the tumor bed to the peripheral breast by dividing
small, medium and large breasts into three subvolumes.
2. METHODS AND MATERIALS
2.1. Virtual Simulation and Treatment Planning
Treatment planning was performed on thirty- one
(21 left-sided and 10 right-sided) T1-2 N0 breast
cancer patients, mean age 60 years (31-78), between
May 16 and July 27, 2013. All patients underwent CTscanning (dedicated Siemens Spirit) following breast
conserving surgery. The images were obtained with the
patients lying supine on a breast board with the
ipsilateral arm abducted above their heads. Before the
CT scan was performed, skin marks were made with a
fiber tip marker to locate the isocenter and to enable
© 2015 Pharma Publisher
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Global Journal of Breast Cancer Research, 2015, Vol. 3, No. 2
patient repositioning during treatment. Radiopaque
catheters and markers were placed around the
palpable glandular breast tissue and the scar of the
tumor bed. Patients were scanned from the level of the
larynx to the level of the upper abdomen including both
lungs, with a 5 mm slice thickness. The CT data for all
patients were transferred to the iPLAN 3D treatment
planning system (TPS), BrainLab 4.5 version.
The clinical target volume of the whole breast
(CTV_breast) was drawn on each CT slide following
the radiopaque catheters and excluding the pectoralis
major and ribs. The PTV of the whole breast
(PTV_breast) was generated by adding a 5 mm margin
around the CTV_breast.
Silvia Beatriz Zunino
2.2. Definition of Sub-Volumes
Sub-volume 1 was defined as the CTV of the
simultaneous integrated boost (CTV_SIB). The PTV of
the CTV_SIB (PTV_SIB) was generated by adding a 5
mm margin.
Sub-volume 2 was defined as the proximal CTV
(CTV_ proximal) which is the 3 cm expansion from the
CTV_SIB across the CTV_ breast. The proximal PTV
(PTV_proximal) was generated by adding a 5 mm
margin to the CTV_proximal.
Sub-volume 3 was defined as the CTV of the distal
breast (CTV_distal). It was generated by the
subtraction of the CTV_proximal from the CTV_breast.
Figure 1: The central volume in red is the CTV_SIB. The orange volume surrounding the red one is the CTV_proximal. The
green volume is the CTV_distal.
Breast Sub-Volumes
The PTV_distal was generated by adding a 5mm
margin to the CTV_distal (Figure 1).
For consistency, all volumes were confined to 5mm
from the skin surface.
The dose prescribed to the PTV_SIB ranged from
62, 5Gy to 66Gy and to the PTV_proximal and
PTV_distal were 50Gy and 46Gy respectively.
Radiation therapy was delivered in 25 fractions over 5
weeks.
2.3. Breast Size and Volume
In order to evaluate the feasibility of sub- volumes in
any breast size, the whole breasts of the 31 patients
were divided into three groups: small (160-400cc),
medium (>400-700cc) and large (>700cc). These
volumes in cc were calculated by the TPS.
2.4. Dose Evaluation and Analysis
The dose volume histograms (DVHs) and the dose
distribution of D95% (dose received by 95% of the
breast volume), were analyzed and compared for each
sub-volume.
The homogeneity index (HI) was used to assess
dose homogeneity in the PTV_SIB. HI was defined
following the formula used by Myonggeun Yoon et al.
[9].
2.5. Organs at Risk (OARs)
The delineation of the heart and lungs was based
on the RTOG guidelines [10].
The heart was drawn encompassing the
myocardium and the whole pericardium from the lower
part of the pulmonary trunk to the apex. Both
lungs were delineated on the CT simulation images.
According to these guidelines, the dose-volume
constraints used for the lung and the heart were V20Gy
< 10%, and V10Gy <10%, respectively.
Global Journal of Breast Cancer Research, 2015, Vol. 3, No. 2
29
to the whole breast volume were defined as segment_1
by placing the isocenter in the middle of the breast
volume. The dose was calculated for open fields and
normalized
in
the
isocenter.
Two
volumes
corresponding to the isodose of 105% and 115% were
created and used to define additional segments where
these volumes were blocked (segment_2 and
segment_3). The segment weights were manually
adjusted to improve dose homogeneity within the
volume. Additional open fields (medial and lateral) were
created and conformed to the PTV_proximal
(segment_4). The weights of segment_1 and
segment_4 were optimized to obtain the desired breast
dose differentiation between the proximal breast and
the distal breast. Using the breast isocenter plan, the
PTV_SIB was irradiated by a 3-field technique. Two
segments per incidence were used to improve dose
homogeneity. Treatment was delivered following the
sequence of the field angle in only one rotation
direction, maintaining the patient set-up during
treatment. Twenty-one consecutive left-sided clinical
plans which had been drawn to irradiate the three subvolumes were re-planned for the 2-volume
conventional technique (whole breast and boost) to
compare the heart median dose and the dose received
by the left lung.
2.7. Statistical Methods
In order to compare D95% for PTV_SIB,
PTV_proximal and PTV_distal, the Friedman test was
used [12]. The Kruskall-Wallis [12] one way analysis of
variance was used to compare the mean size and
range for the whole breast volume and sub-volumes,
the percentage of each CTV_ sub-volume in relation to
the whole breast in small, medium and large sizes, as
well as the PTVs covered by D95% for each breast
size. The dose received by the heart and the left lung
with both techniques were compared with the Student´s
t test [13]. All statistical analysis was performed using
Statistica software [14]. Differences were considered
significant when probability values less than 5% were
obtained (p<0.05).
2.6. Simplified Intensity - Modulated Technique
This treatment technique, known as simplified
intensity-modulated (sIMRT) with field-in-field modality,
consists of multiple segments with forward weight
optimization, as described by Kestin L. et al. [11]. A 6
MV photon beam produced by a linear accelerator with
a multileaf collimator (MLC) was used. An open medial
field and a lateral opposing tangential field conformed
This study was performed after approval by the
Institution Bioethics Committee and written informed
consent was obtained from all patients.
3. RESULTS
A total of 31 women with early breast cancer (21
left, 10 right) referred for radiation therapy were
planned with the 3 volume technique. The size of each
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Global Journal of Breast Cancer Research, 2015, Vol. 3, No. 2
Silvia Beatriz Zunino
Table 1: Mean Size and Range for the whole Breast Volume and Sub-Volumes
Volume
Small (n=15) cc
Medium (n=8) cc
Large (n=8) cc
p
CTV_breast
295.3 (160.8-391.0)
613.0 (441.2-698.7)
803.3 (708.7-1164.9)
0.0000
CTV_SIB
56.1 (27.6-92.2)
66.9 (20.2-144.1)
89.6 (36.3-154.2)
0.0002
CTV_proximal
188.0 (92.5-266.4)
337.6 (163.8-463.9)
389.6 (240.5-638.4)
0.0001
CTV_distal
236.4 (137.8-353.5)
465.5 (106.0-728.8)
591.1 (399.8-797.9)
0.0001
Table 2: Percentage of CTV Sub-Volumes in Relation to the CTV_Breast in each Size
Sub-volume
Breast Size Group
p
Small (n=15) %
Medium (n=8) %
Large (n=8) %
SIB
13.5 (7.6-21.5)
8.7 (3.0-16.6)
9.4 (3.8-17.8)
0.0402
Proximal
45.2 (25.3-70.0)
44.9 (19.7-75.3)
39.4 (27.6-47.5)
0.5284
Distal
57.1 (30.8-76.6)
58.4 (19.2-85.2)
60.3 (46.2-82.8)
0.9235
Figure 2: Box plot shows the mean value, the mean ± standard deviation (SD) and the min-max values for PTV_SIB D95%,
PTV_proximal D95% and PTV_distal D95%, respectively.
sub volume calculated in cc for small, medium and
large breasts is shown in Table 1.
As observed in Table 2, the relation between the
subvolumes and the whole breast volume is similar for
the three sizes.
The three sub-volume technique allowed for a
significant (p=0.0000) gradual dose decrease from
PTV_SIB to PTV_distal (Figure 2).
The D95% for PTV_SIB, PTV_proximal and
PTV_distal were 62.6Gy (60.5-65.6 Gy); 49.3 Gy (47.051.1 Gy) and 45,5 Gy (43.2-47.3 Gy), respectively.
There was no difference in dose distribution
homogeneity
in
PTV-SIB,
PTV_proximal
and
PTV_distal for the three breast sizes (Table 3).
The homogeneity index was lower than 10 in small
(5.8), medium (7.8) and large breasts (6.9).
Breast Sub-Volumes
Global Journal of Breast Cancer Research, 2015, Vol. 3, No. 2
31
Table 3: PTVs Covered by D95% for each Breast Size
D95%
Small (n=15) Gy
Medium (n=8) Gy
Large (n=8) Gy
p
PTV_SIB
62.5 (60.5-65.4)
63.1 (60.7-65.0)
62.0 (60.7-65.6)
0.7406
PTV_proximal
49.6 (47.3-51.1)
48.5 (47.0-49.7)
49.4 (47.3-51.0)
0.0477
PTV_distal
45.6 (43.5-47.0)
45.1 (43.2-45.8)
45.9 (43.8-47.3)
0.1504
As seen in Table 4, in the 21 left breast plans there
was no statistical significant difference in the dose
received by the heart and the left lung between the
conventional technique and the 3-subvolume
techniques. However, the median dose received by the
heart was 1.2 Gy lower with the 3 sub-volume
technique than with the conventional technique.
Table 4: Dose Received by the Heart and the Left Lung
with both Techniques
Techniques /n= 21
Conventional 2 volumes
Heart
Left Lung
V10Gy
Mean Dose
V20Gy
3.7 %
4.7 Gy
8.1 %
3 sub-volumes
3.7%
3.5 Gy
8.1 %
p
1.0000
0.0742
0.9963
4. DISCUSSION
The current study proposes a non-standard three
sub-volume delineation in order to gradually decrease
the dose from the tumor bed to the distal breast. We
found a similar design in a publication by Spruijt et al.
[15] who divided the PTV breast into PTV_boost, PTV_elective
and Transition Structure to compare different IMRT
techniques.
In our trial, the sub-volume division was used for
small, medium and large breasts, achieving gradual
decrease of the dose from PTV_SIB to PTV_distal in all
breast sizes. It should be taken into account that the
dose received by the PTV_SIB and PTV_Proximal are
the doses conventionally used for breast cancer.
The trial by Mukesh Mukesh et al. [8] suggests that
a modest dose reduction to the breast away from the
tumor bed might reduce the rate of fibrosis, shrinkage
and telangiectasia without diminishing tumor control.
The 10-Year Results of the Randomized Boost
Versus No Boost EORTC 22881-10882 Trial
demonstrated that the boost dose significantly
increased the worst reported grade of fibrosis in both
the whole breast and the boost area: the cumulative
incidence of severe fibrosis at 10 years was 4.4% (99%
CI, 3.5% to 5.7%) with boost versus 1.6% (99% CI, 1%
to 2.3%) without boost (p<0.0001) [16].
In order to irradiate the 31 patients included in this
study, we used a simplified intensity-modulated
technique with field-in-field modality, which consists of
multiple segments with forward weight optimization, as
described by Kestin L. et al. [11]. The advantages of
simple IMRT compared with the conventional technique
were proved by Pignol et al. [17] in their multicenter,
randomized trial where they confirmed a dramatic
improvement in the dose distribution homogeneity
using breast IMRT. They also demonstrated that it
translated into a significant 17% absolute reduction in
the frequency of moist desquamation. Later, Mukesh B
Mukesh et al. [18] published the results of another
randomized trial after 5 years of follow-up. They
compared standard radiotherapy with forward-planned
field-in-field dose homogenization and showed that the
patients treated with simple IMRT had better cosmesis
and less risk of telangiectasia than those who had
received standard radiotherapy.
In the 21 consecutive left-sided clinical plans, the
V10 Gy received by 3.7 % of the heart was the same
with both techniques. However, the mean dose to the
heart given by the sub-volume technique was 1.2 Gy
lower than the mean dose delivered by the
conventional 2-volume technique. The concept of mean
dose has been highlighted by Darby et al. [19] who
published that the rates of major coronary events
increased linearly with the mean dose to the heart by
7.4% per Gy (95% confidence interval, 2.9 to 14.5;
p<0.001). In line with this concept, the lower mean
dose received by the heart with our three-volume
technique might have a beneficial effect to prevent
coronary disease.
5. CONCLUSION
The three breast sub-volumes irradiated with
simplified intensity-modulated technique would allow
for a slight but significant gradual decrease of the dose
from the tumor bed to the distal breast. A long-term
32
Global Journal of Breast Cancer Research, 2015, Vol. 3, No. 2
Silvia Beatriz Zunino
follow-up is required to confirm whether this dose
decrease may contribute to reduce toxicities.
[9]
Yoon M, Park SY, Shin D, Lee SB, Pyo HR, Kim DY, et al. A
new homogeneity index based on statistical analysis of the
dose-volume histogram. J Appl Clin Med Phys 2007; 8 (2) 917.
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Received on 12-08-2015
Accepted on 18-11-2015
Published on 31-12-2015
DOI: http://dx.doi.org/10.14205/2309-4419.2015.03.02.2
© 2015 Silvia Beatriz Zunino; Licensee Pharma Publisher.
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