Introduction
Bilateral Breast Carcinoma (BBC) is a rare entity with
an incidence of synchronous carcinoma being 2-5%
of all breast malignancies. Despite the infrequency of
cases of synchronous bilateral breast cancer (SBBC), the numbers of SBBC diagnoses have been showing an
upward trend along with the increase in breast cancer
cases.[] Against this background, research on prognosis
and treatment is still ongoing. However, to our
knowledge, no definite radiation therapy has been reported
for SBBC yet.
Compared to unilateral breast cancer radiotherapy,
the treatment planning and dose delivery of the
BBC is very complex and time-consuming. One of
the standard treatment techniques for BBC is 2-dimensional
radiation therapy (2DRT) or 3-dimensional
conformal radiation therapy (3DCRT) with
tangential beam irradiation.[,] It is rather difficult
to protect organs at risk (OARs) that lie in the same
direction as the target. For complex treatment volumes,
such as SBBC, recent trends have shown that
intensity-modulated radiation therapy (IMRT) and
volumetric-modulated arc therapy (VMAT) are applied.[,] Once IMRT and VMAT have been used
for SBBC radiation therapy, the problems associated
with isocenter and junction can be addressed. There
have been only a few studies of treatment for SBBC,
but there have recently been several studies comparing
conformal radiation therapy (3DCRT) and IMRT
treatment plans in SBBC, [] as well as a study comparing
IMRT with Rapid Arc (RA) treatment plan.[]
Another study was conducted to evaluate treatment
plans with complex treatment volumes using helical
tomotherapy.[] Thus, this is the first planning case
reported in the literature on all four techniques (FiF,
IMRT, VMAT and HT) for synchronous bilateral
breast cancer patients.
In this study, we aimed to compare the technical
feasibility and benefits of two different helical intensity-
modulated RT (RapidArc VMAT and TomoTherapy)
with three dimensional conformal (Field-in-field
(FiF)) and multi-field dynamic (sliding-window)
IMRT for SBBC patients.
Methods
Patients and Planning Objectives
Two different patient cases were reported in this study
and patients" consent was obtained for this report. The
first patient (Pat#1) was a 48-year-old premenopausal
female with bilateral ductal breast carcinoma. She underwent
bilateral breast-conserving surgery and sentinel
lymph node biopsy (SLNB) (right breast:T2N0M0
stage IIA, left breast:T1bN0M0 stage IA). The Pat#2
was a 54-year-old postmenopousal female with earlystage
SBBC. She underwent bilateral breast-conserving
surgery and SLNB (right breast:T1bN0M0 stage IIA,
left breast: T1cN0M0 stage IA). With both patients,
chemotherapy consisted of four cycles of doxorubicin
and cyclophosphamide (AC). They also received hormonotherapy
for five years.
Both patients were imaged supine with a CT scanner
(Siemens Somatom Spirit) in the treatment position (both arms up). CT was performed at 3-mm slice
spacing. For patients, the clinical and planning target
volumes (CTV and PTV) of the right and left were
delineated on the CT data. The CTV included visible
breast parenchyma, excluding the muscles and ribs, retracted
5 mm from the skin into the body. The PTV
comprised the CTV with a 10-mm circumferential
margin to allow for daily set-up variations and potential
intrafraction thoracic wall motion, also retracted
by 5 mm from the skin into the body.
The critical structures delineated were both lungs,
heart, spinal cord. The heart was contoured from below
the level of the great vessels up to the diaphragm.
The lungs were contoured in the appropriate lung window
setting (width 1600, level 400). The volumes of the
PTVs and lungs were shown in Table 1. The goal of all
plans was to cover 95% of PTVs with 100% of the prescribed
dose.
Table 1: The volumes of the PTVs and lungs in cases
Planning Techniques
Three different treatment planning techniques were
generated by medical physicists on the Eclipse treatment
planning system (TPS) (Version 11) for Varian
Trilogy linear accelerator with Millenium MLC. 6 MV
photon energy and Anisotropic Analytical Algorithm
(AAA) were used for all planning techniques. The dose
calculation grid was set to 2.5 mm.
Patients were also planned on the Tomotherapy
planning system Hi art (Version 4.2.3). There was no
overlapping of treatment fields in any of the plans.
Neither bolus nor other techniques were used for skin
doses.
Field in Field
Two fixed main tangential fields which have sub-fields
were used for both breasts separately to achieve more
homogeneous dose distribution in PTVs. All fields
were shaped to cover their PTVs with fall offs to the
surfaces of the breasts of both patients. Single isocenter
was used for both breasts; we used 310°-130° and
50°-230° beam angles for left and right breasts, respectively.
Intensity-modulated Radiation Therapy (IMRT)
The dynamic sliding window method with fixed gantry
beams was used for left and right breasts with angles
310°, 325°, 300°, 100°, 115°, 130° and 55°, 40°, 25°,
260°, 245°, 230°, respectively. Two isocenters were used
for both patients. Fluence transmission factors for each
field were optimised using the fluence editor.
Volumetric Modulated Arc Therapy (VMAT)
Single isocenter method was used for VMAT plans.
Two arcs for each breast were generated in the planning
of both patients. For the first patient, clockwise
(CW) and counterclockwise (CCW) 190° arc (40° to
210° and 320° to 150°), for the second patient 241° arc
(300° to 179° and 60° to 181°) were used. Collimator
angle was set to 30° for CW and 330° for CCW.
Helical Tomotherapy
In HT planning 2.5 cm field width, 3.0 modulation
factor and 0.215 pitch value were used. To reduce the
bilateral lung and heart doses, a directional and complete
block was used. In addition, to prevent high doses
out of the breast wall, we used ring contour around the
breast wall.
Treatment Delivery with Image-Guidance
Image-guided radiation therapy (IGRT) significantly
improves the accuracy of radiotherapy. IGRT plays
an essential role in the accurately delivery of a highly
confirmed dose to target. Varian Trilogy's On-Board
Imager (OBI) kV imaging system provides a wide array
of imaging modalities, including kV, MV, cone-beam
CT (CBCT) and fluoroscopy. For the reported patient
cases, daily kV?CBCT images were taken to set up the patients. 3 mm slice distance and 512x512 reconstruction
volume were used for CBCT imaging. After doing
necessary corrections on the images, patients were
treated.
Evaluation Tools
The evaluation of the plans was based on a dose-volume
histogram (DVH) analysis. For PTV, the mean
dose, near-max dose D2 and near-min dose D98 were
reported. The conformity index (CI) is defined as the
ratio of the volume to 95% of the prescribed dose to
the PTV.[,] The homogeneity index (HI) is defined
as the ratio of the dose difference of 2% and 98% to
the PTV to the prescribed dose.[] Lower HI values
indicate more homogeneous target doses. The Dmean,
V20Gy, and V5Gy for the lungs and V35Gy, V25Gy,
and Dmean for the heart were compared. To evaluate
objectively the efficiency of the treatment plans,
the beam times, the treatment times (including setup
time), and the monitor units (MUs) for each plan were
compared.
Results
The prescribed dose for SBB RT was 50 Gy in 2 Gy fractions
to the PTVs. The goal of all plans was to cover
%95 of PTVs with %100 of the prescribed dose (Fig.
1). Table 2 shows the dosimetric results achieved in all
four techniques for these two patients" CT dataset. In
this case of SBBC, HT appeared to be more suitable
than the other techniques, providing better conformity
and homogeneity index (HI) (Table 3). FinF did not
have as good conformity, or homogeneity as HT, IMRT
and VMAT.
Fig 1: Axial dose distributions for patient 1 with a dose
colour wash of 47,5 Gy for all treatment techniques.
(a) FiF (b) IMRT (c) VMAT (d) HT.
Table 2: Dose distribution in organs at risk and treatment time in all planning techniques
Table 3: The comparison of PTV coverage for FinF, IMRT,
VMAT and HT using dosimetric parameters
Lungs
For the first patient, the mean dose (Dmean) to total
lungs was 10.8 Gy, 11, 10.3 and 12.2 Gy for FinF, inverse
IMRT, HT and VMAT, respectively. D mean in
the total lung was similar for HT and FinF, but worse
for VMAT and IMRT. The Dmean to lungs for the
Pat#2 was slightly increased using VMAT, from 10
Gy to 14.5 Gy, when compared to the HT technique.
In this case, the volume of the lungs covered by the
dose of 5 Gy (V5Gy) in VMAT planning was on average
85%, while the respective volume in Helical tomotherapy
was only 45,5% (FinF,], VMAT
was related with the most unfavourable dose deposition
in the total lung, concerning Dmean, V5,V10 in
the present study.
Heart
In the present study, the mean dose to the heart was 5.6,
5.7, 7.9 and 6.8 (Pat#1); 4.6, 8, 8.4 and 6.3 (Pat#2) for FinF, IMRT, VMAT and HT, respectively, with VMAT
providing the poorest outcome. Concerning dose distribution
on heart, the percentage of volume at high
doses, such as V35Gy and V25Gy, was approximately
70-88% lower for HT and approximately 95-97% lower
for VMAT than for FinF and iIMRT.
Monitor Units and Treatment Time
Concerning MUs, HT had the highest total motor units
in patient 1 (MUs:8462) and patient 2 (MUs:14555)
(FinF2). Both
patients underwent bilateral breast radiotherapy with
FinF technique. The cosmetic outcome was good and
no breast oedema, erythema, or fibrosis were reported
during routine follow-up.
In the literature, dosimetric studies using VMAT
and tomotherapy demonstrated the feasibility of delivering
radiotherapy in bilateral breast cancer patients.[,] The findings showed that h-VMAT and
hybrid intensity-modulated radiation therapy (h-
IMRT) used for breast cancer patients reduce low dose
spillage to the lung and heart.[] Improved survival
in early breast cancer patients has led the radiation
oncology fraternity to focus on reducing the dose to
the heart and lungs. Quantitative analysis of normal
tissue effects in the clinic for lung clearly emphasizes
the need to limit the V5Gy to less than <60%, V20Gy
less than 30-35% and the mean lung dose (MLD) to
<23 Gy.[]
Darby et al.[] conducted a study to assess the risk
of ischemic heart disease in women after radiotherapy
for breast cancer. They cautioned about the potential
risk for cardiac injury even at low doses, with a relative
risk of 7.4% per Gy increase in adverse cardiac events.
Furthermore, to avoid long-term cardiac mortality, extensive
blocking of the heart is usually needed with the
traditional field arrangements. This will require the acceptance
of incomplete dose coverage of the PTV. With
the VMAT and HT techniques, the high dose areas in
the heart can be avoided without compromising the
PTV dose coverage.
Yusoff et al.[] compared the 3DCRT and IMRT
treatment plans for SBBC patients. It was reported that
both treatment plans showed similar results for PTV
coverage, whereas for OAR dose distributions to the
lungs and heart, IMRT was superior. FinF, compared
with IMRTand VMAT, it had advantageous concerning
OAR low dose distribution and mean dose of heart. HT
and FinF provided similar dosimetric results for OARs,
but the total lung V20Gy and heart V25Gy/V35Gy
were improved with HT.
Kim et al. showed that among the SBBC radiotherapy
treatment plans, IMRT was superior to 3DCRT and
VMAT concerning PTV dose distribution, whereas
VMAT showed the most outstanding treatment efficiency.[] On the contrary, VMAT was inferior to
iIMRT, HT and FinF concerning the dose in organs at
risk, especially for low dose levels (V5Gy, V10Gy) and
mean dose in the present study.
In a series of 14 patients with SBBC, Ekici et al. reported
that HT was well-tolerated, with high HI and CI
and low irradiation doses to the lungs and heart.[]
Overall, the HT plans decreased the doses to the lungs
and heart and increased the dose homogeneity in the
treatment volume in our study, and it is similar to the
above reports.
Conclusion
In the present planning case report, all four techniques
achieved acceptable target coverage while avoiding
the field overlapping issues. The HT achieved better
sparing of lungs and heart in the low dose region. It is
difficult to suggest a clear guideline or a protocol for
bilateral breast cancer plan based on the TPS result
from this study alone. This study is expected to provide
useful resources for establishing future treatment
guidelines for bilateral breast cancer.
Informed consent: Patients provided informed consent for
this case report and they were requested a copy of the signed
consent to publish.
Peer-review: Externally peer-reviewed.
Conflict of Interest: No potential conflicts of interest relevant
to this article are reported.
Financial Disclosure: This research did not receive any specific
grant from funding agencies in the public, commercial,
or not-for-profit sectors.
Authorship contributions: Concept - Z.D.; Design - Z.D.,
Ş.E., O.A.; Supervision - A.K.D., N.D.A.; Materials - Z.D.,
Ş.E., O.A., F.K., A.K.D.; Data collection &/or processing -
Z.D., Ş.E., O.A., F.K., A.K.D., N.D.A.; Analysis and/or interpretation
- Z.D., Ş.E., O.A., F.K.; Literature search - Z.D.,
Ş.E.; Writing - Z.D., Ş.E.; Critical review - Z.D., Ş.E.
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