METHODS
Radiotherapy was planned with three different techniques simulated images of 30 breast cancer patients
with negative lymph nodes who underwent breast-conserving surgery.
RESULTS
The maximum and minimum doses, homogeneity and conformity index and cold-zone volumes were
found to be different in all three techniques (p<0.001). The PTV boost maximum doses and homogeneity
index were found to be different (p<0.001). The maximum non-PTV dose (110% volume) and the
hot zone volumes grasped by these doses, the V5 volume of the body and V5 volumes, outer of PTV
were found to be statistically significant for all three techniques (p<0.001). A statistically significant difference
was found between the three techniques concerning the ipsilateral lung V5 and V20 volumes,
the contralateral lung V5 and V10 volumes and the counter breast maximum and mean doses (p<0.001).
The mean and V10 volume of the heart was statistically significant (p<0.001), while the left breast irradiation
and mean values were not statistically significant between the three techniques (p=0.529).
However, there was a statistically significant difference in the V10 volume of the left breast irradiation
between the three techniques (p=0.033).
CONCLUSION
According to 3D-CRT, it is possible to achieve better dose distribution and dose homogeneity with Tomo-
helical and direct IMRT. Low dose volumes are high with tomo-helical IMRT. Tomo-helical IMRT
planning provides better ipsilateral lung and heart doses but causes an increase in heart dose/contralateral
breast and for right breast irradiation causes an increase in heart dose.
Keywords: Breast cancer; tomotherapy-direct IMRT; tomotherapy-helical IMRT; three-dimensional conformal radiotherapy
Conventional radiotherapy devices can deliver a wide range of radiation in only a few angles. However, with the advances in technology, various methods, such as three-dimensional conformal RT (3D CRT), density-regulated RT (IMRT) and non-IMRT conformal techniques (forward-IMRT, Direct Aperture Optimization, and Hybrid IMRT), have been applied in breast cancer treatment.
The Tomo-helical/direct IMRT method, which is a
form of IMRT application, has been found in the treatment
of breast cancer.[
In the study comparing the plan quality and secondary
malignancy risks of five different treatment
techniques (volumetric modulated arc therapy, IMRT,
3D-CRT, Tomo-helical, and Tomo-direct IMRT), the
Tomo-helical IMRT plan provides a better plan quality
compared to other techniques and reported that secondary
malignancy provides the lowest lifelong attributable
risk for normal tissues (internal organs, such as
the ipilateral lung and non-field organs). Therefore, it is
thought that irradiation with helical tomotherapy may
be a better treatment method in young patients with a
long life.[
The present study aims to compare the dosimetric
methods of 3D-CRT, Tomo-helical IMRT and Tomo-Direct IMRT in intact breast irradiation of patients undergoing
BCS for breast cancer.
Radiotherapy was planned with three different techniques in 30 breast cancer patients with negative lymph nodes who underwent breast-conserving surgery. A total of 90 plans were created: three plans per patient (3D-CRT, Tomo-helical and direct plans).
Treatment Planning
The breast contour included all glandular breast tissue.
The cranial border was contoured below the head
of the clavicle at the insertion of the second rib. The
lateral border was defined by the midaxillary line. The
medial border was defined at the edge of the sternum.
The caudal border was defined by the loss of breast tissue,
and the anterior border was extracted a few millimeters
(3 mm) from the surface of the skin.
The lumpectomy cavity included seroma, surgical
clips, and notable differences in the glandular breast
tissue. The lumpectomy cavity with a margin of 0.5-
1cm was defined PTVboost (planning target volume).
Figure
The heart, lungs, spinal cord, and contralateral
breast were contoured as Organs at Risk (OAR). Figure
Three-dimensional conformal radiotherapy planning
was performed using the Eclipse (ver. 8.6; Varian
Medical Systems, Inc. Palo Alto, CA, USA) software
program. Intact breast and boost fields were carried
out using a 6?18 MV photon beam. The 3D-CRT plan
consisted of opposed tangential beams and added subfields
created by MLC for dose compensation (FiF). In
the FiF segmental IMRT technique, the same beam orientation
as 3D-CRT can be used. In the FiF technique,
the homogeneous dose distribution was obtained by
MLC instead of wedge filters by closing the hot areas
and adding new sub-areas to the cold regions. In the
planning of the boost zone, the electron field or minitangential
field technique with appropriate energy was
used.
The tomotherapy plans were performed using a
Tomo-H VoLO planning system (Accuray Inc. Madison,
WI, USA). All Tomo-helical and direct IMRT
plans were generated using the same constraints (field
width: 2.5cm, pitch: 0.215, modulation factor: 2-5).
The Tomo-Direct IMRT technique uses a static gantry
position. The dynamic collimator is similar to the classic
IMRT using a sweeping window, and it is shifted
through simultaneous table movements along the patient
beam area. In the direct IMRT plans, a 4-6 area
and the 2.5cm-wide plan was made. In the Tomo-helical
IMRT technique, the target volume irradiation
was carried out helically with a fan-shaped narrowed
fan beam in continuous rotation. In the helical IMRT
plans, a critical block was applied to the critical organs,
and an area of 2.5cm was planned.
The target volume coverage was selected as D98 in
both plans. In these treatment plans, 98% of the dose
defined for the PTV was provided. For all three techniques,
50 Gy was planned in 25 fractions in the intact
breast and 60 Gy in 30 fractions in the tumor bed.
The dose limitation of the critical organs was ipsilateral
lung V5 <60% and V20 <22%, heart mean <5 Gy, and
contralateral breast mean <3 Gy.
Evaluation of Radiotherapy Plans
In radiotherapy, a homogeneous dose distribution
is aimed at the target, and the evaluation is made by
looking at the doses taken by 2% (D2), 50% (D50), and
98% (D98) of the PTV, whether the defined dose encapsulates
the target (HI=D2-D98/D50) or not. As this
value approaches zero, the homogeneity of the dose
distribution in the PTV appears to be ideal.
According to ICRU 83, the conformity index is
calculated by dividing the volume of PTV wrapped by
the specified reference dose by the total PTV volume,
and the reference dose is expected to envelop the entire
PTV. The ideal value of CI is 1. A CI close to 1 indicates
that the dose covered by the target volume is good. The
PTV volume, which receives 95% of the defined dose,
is obtained by the PTV division (CI=TVprescribed/
PTV).
For the critical organs, the mean dose and V10
volume of the heart, the mean dose of the ipsilateral
and contralateral lung, the V5, V10, and V20 volumes,
and the maximum and mean dose of the contralateral
breast were used to compare the techniques.
Statistical Analysis
All patients underwent computed tomography (CT)
with a wingboard in the supine position for treatment
planning. They had a planning CT scan at a 3-mm slice
thickness. The planning target volume was contoured
according to the Radiation Therapy Oncology Group
(RTOG) atlas.[
All volumes were compared with the dose-volume histograms.
For the target volumes, the Dmax, Dmin, cold
zone (cc), conformity index (CI), and homogeneity index
(HI) values were compared. The dose suitability
and homogeneity were measured and estimated according
to the International Radiation Unit and Measurement
Commission (ICRU) 83.[
We performed all analyses using the SPSS (Statistical
Package for Social Sciences) software (Version 22.0;
SPSS Inc., Chicago, IL, USA). Frequency analyses and
Kruskal-Wallis tests were used to statistically analyze
the data. We considered the differences to be statistically
significant at p-value<0.05.
A statistically significant difference was found between the three techniques concerning the PTVboost maximum doses and homogeneity index (p<0.001). Dose homogeneity was best achieved using the Tomohelical IMRT technique. The cold zone was not present in all three techniques.
The maximum non-PTV dose (110% area volume) and the hot-zone volumes grasped by these doses were statistically significant (p<0.001). The V5 volume of the body and the V5 area, except the PTV, were found to be statistically significant for all three techniques (p<0.001). 3D-CRT was superior for the V5 volume of the body.
Comparisons of Tomo-Direct IMRT, Tomo-helical
IMRT, and 3D-CRT planning (target volumes, out of
PTV volumes and body) are shown in Table
Organ at Risk
The V5 and V20 Gy dose volumes of the ipsilateral lung
doses were different and statistically significant in all
three techniques (p<0.001). In the Direct-IMRT planning,
the V5 value was lower than the other two techniques
(p<0.001).
The V5 and V10 Gy volumes of the contralateral lungs were found to be different between the techniques, and the V20 Gy volume was not determined in the plans made with all three techniques (p<0.001).
In the mean-breast irradiation, the mean and 10 Gy field volume of the heart was statistically significant (p<0.001), while the left-breast irradiation, mean values were not statistically significant between the three techniques (p=0.529). However, there was a statistically significant difference in the V10 and V25 Gy dose volumes of the left-breast irradiation between the three techniques (p=0.033 and p=0.014).
There was a statistically significant difference between the three techniques for the maximum and mean dose of the contralateral breast (p<0.001).
Table
Target and out of PTV Volumes
In this study, the 3D-CRT, Tomo-helical and Tomo-
Direct IMRT techniques were compared in 30 lymphnode-
negative patients undergoing lumpectomy. When
the results of these three techniques were analyzed, it was
observed that the tomotherapy techniques improved the
target volume better than 3D-CRT, but the dose homogeneity
was best achieved with the Tomo-helical IMRT
technique. Again, the maximum and minimum doses
and the cold-zone values in the target volume were
obtained by the best tomotherapy techniques (Fig.
When the figure is examined, it is seen that the V5 dose volumes are larger in Tomo-helical IMRT planning.
Goddu et al. compared helical tomotherapy with
3D-CRT planning. The chest wall/breast, supraclavicular
and intramammary lymph nodes were contoured
and planned for both techniques in 10 lymph-nodepositive
left-breast cancer patients. It has been shown
that Tomo-helical IMRT envelops the target better than
3D-CRT and provides better dose homogeneity.[
Reynders et al. compared 3D-CRT and tomotherapy
(helical and direct) RT planning in eight breast
cancer patients. In the study, 6-7 plans were prepared
for each patient in the supine and prone position of the
patients, left-right tumor, lymph-node positive, lymphnode
negative, MRM and MKC were performed and
three techniques were compared. Researchers have reported
that Tomo-helical and direct planning provides
a dose distribution equal to or better than 3D-CRT in
the target volume and organs to be protected.[
In the dosimetric study conducted by Schubert et
al., the left whole-breast RT planning was performed
with different IMRT techniques. They compared 3DCRT
planning. In this study, the left-breast RT planning
of 10 patients was performed with the 3D-CRT,
Tomo-helical, Tomo-direct IMRT, inverse-IMRT, and
forward-IMRT techniques. As a result, the maximum
doses of the target volume were found to be lower using
the IMRT techniques than the 3D-CRT. All the methods evaluated provided adequate coverage of the
dose in the target breast. However, the dose homogeneity
was found to be more successful using the Tomohelical
and Tomo-direct IMRT techniques than 3DCRT.[
Shiau et al. compared Tomo-helical IMRT and hybrid
IMRT in 30 early-stage left-breast cancer patients.
The target coverage of both methods was similar. However,
CI and HI were better detected in Tomo-helical
IMRT.[
In a letter written by Arsene-Henry et al., it states
that it covers the target with adequate and homogeneous
dose distribution and reduces OAR doses. However,
they stated that the risk of a secondary malignancy
might be increased because of the low dose volumes
taken from the counter lung, the opposite breast, and
other normal tissues in Tomo-helical IMRT.[
Ashenafi et al. compared chest-wall irradiation after
a mastectomy with Tomo-helical IMRT and a conventional
method (electron-photon beam mixture). In
their study, it was shown that the dose homogeneity
of the target volume was better achieved in Tomo-helical
IMRT, but the V5 and V25 volumes of the body
were significantly wider in the planning of Tomo-helical
IMRT (p<0.001). In addition, they found that a
secondary cancer complication probability was significantly
higher for Tomo-helical IMRT planning.
[
Organs at Risk
In the dosimetric study of Schubert et al., comparing
the dose distribution and risky organ protection
provided by modern RT techniques to the target, all
the techniques (3D-CRT, Tomo-helical, Tomo-direct
IMRT, inverse-IMRT, forward-IMRT, hybrid IMRT) breast) provided adequate doses. The maximum doses
of the ipsilateral lung and heart were found to be the
lowest in Tomo-helical IMRT, but the mean doses of
both structures were found to be highest in Tomo-helical
IMRT. Compared to Inverse-IMRT, Tomo-direct
IMRT, and 3DCRT, the IMRT techniques reduced the
mean and maximum doses of the ipsilateral lung. Tomo-
helical, tomo-direct and inverse-IMRT were able
to reduce the maximum doses in the target and normal
tissues, but low-dose volumes of normal tissue were
found to be high in Tomo-helical IMRT.[
In another dosimetric study comparing Tomo-helical
IMRT and Tomo-3D-CRT, which are the options of
tomotherapy, it was observed that Tomo-helical IMRT
was superior concerning contralateral breast and heart
doses.[
In a study in which Goddu et al. compared Tomohelical
IMRT and 3D-CRT planning and aimed to
protect lung, heart and breast against, according to 3DCRT
planning, left lung V20, mean dose of heart and
right breast dose It was found to be lower.[
Coon et al. compared 3D-CRT, IMRT, and Tomohelical
IMRT in 15 left-breast cancer patients with unfavorable
heart anatomy after a lumpectomy. The mean
heart dose and ventricular volume dose were lower
in IMRT and Tomo-helical IMRT planning than 3DCRT.
However, the counter-breast dose was found to
be higher in Tomo-helical IMRT.[
In a 2015 dosimetric study, five different methods,
volumetric modulated arc therapy, forward-IMRT, inverse-
IMRT, 3D-CRT, and Tomo-helical IMRT, were
compared. In this study, 15 patients with left-breast
carcinoma and who underwent MKC were evaluated.
Helical IMRT was found to have a lower organ dose
risk, including heart, ipsilateral lung, and LAD. However,
the volumes receiving low-dose Tomo-helical
IMRT are higher than other methods.[
In their dosimetric study (3D-CRT vs. Tomo-helical
and direct IMRT), Reynders et al. reported that tomotherapy
techniques could achieve an equal or better
dose distribution to 3D-CRT in OAR.[
In our study, the dose of the ipsilateral lung V5 was
found to be statistically significantly lower than Tomohelical
and Direct IMRT compared to 3D-CRT. The V20
dose of the ipsilateral lung was the lowest Tomo-helical
IMRT compared to the other two methods. However,
the counter-lung V5 and V10 values were determined
only in Tomo-helical IMRT, and it was observed that
these methods did not take the dose in the other methods.
In our study, when the cardiac techniques were
compared concerning cardiac doses, the cardiac doses
(mean and V10) were higher in the Tomo-helical IMRT
planning, which caused wide low-dose volumes in the
right-breast planning. However, in the left-breast planning,
the V10 and V25 doses receiving volume of the
heart was found to be the lowest Tomo-helical IMRT
planning. In our study, when the techniques were examined
concerning counter-breast doses, the maximum
dose of the counter breast was observed in the lowest Tomo-direct IMRT planning. In Tomo-helical IMRT and
3D-CRT planning, the maximum dose of the opposite
breast was found to be similar. The mean-breast counter
dose was found in the lowest Tomo-direct IMRT, while
the highest counter breast mean dose was found in Tomo-
helical planning. Figure
For ipsilateral lung and heart doses, Tomo-helical IMRT planning provides good protection but causes an heincrease in heart dose in the contralateral breast, contralateral lung and right breast irradiation (due to the high body"s low-dose volumes). This disadvantageous situation in OAR with Tomo-helical IMRT seems to be solved by Tomo-direct IMRT planning.
Peer-review: Externally peer-reviewed. Conflict of Interest: The authors have no conflicts of interest to declare.
Ethics Committee Approval: The study protocol was approved by the institutional review board. (Number: 2017- 04/14, Date: 19.04.2017)
Financial Support: The authors declared that this study has received no financial support.
Authorship contributions: Concept - E.E.; Design - E.E.; Supervision - E.E.; Funding - None; Materials - B.Ö.; Data collection and/or processing - R.B.; Data analysis and/or interpretation - E.E.; Literature search - E.E.; Writing - E.E.; Critical review - B.Y.
