International Journal of Cancer Therapy and Oncology [605427]

International Journal of Cancer Therapy and Oncology
www.ijcto.org
Copyright ©Moorthyet al. ISSN 2330 -4049Suresh Moorthy1, Hamdi Sakr1, Shubber Hasan1, Jacob Samuel1, Shaima Al-Janahi1,
Narayana Murthy2
1Department of Oncology & Hematology, Salmaniya Medical Complex, Kingdom of Bahrain
2Department of Physics, Acharya Nagarjuna U niversity, Guntur, India
Received September 05, 2013; Revised October 02, 2013; Accepted October 08, 2013; Published Online October 10 , 2013
Original Article
Abstract
Background and purpose: 3-dimensional conformal therapy (3DCRT) is widely employed radiation therapy technique for breast
cancer,butthere isstillneed to minimize the doses to organ at risk (OAR) using 3DCRT. A few clinical studies have discussed
using intensity modulated radiation therapy (IMRT) to address this shortfall. Simultaneous integrated boost (SIB) has been us ed
in head and neck and prostate cancer, and there is a growing interest i n using SIB for breast cancer too. This study aimed to
compare SIB -IMRT versus SIB -3DCRT for breast cancer patients. Materials and Methods: SIB-3DCRT treatment plans were
created for 36consecutive patients. Dose was prescribed as 45 Gy in 25 fractions to theplanning target volume ( PTV)-1 and 60
Gy in 25 fractions to PTV -2.Treatment plans were normalized to 95% of PTV volume receiving 95% of the prescription dose.
Theconformity index ( CI),homogeneity index ( HI),lung dose, heart dose, left anterior descending artery(LAD) dose ,andlow
dose volume and integral dose of normal healthy tissue were recorded and analyzed. Results:With the use of IMRT technique,
there was an improvement in CI ( 0.14) when compared to CI of 3DCRT (0.18; p =0.01). However, there was no significant di f-
ference in the HI (p = 0.45).On average, the V20Gyof ipsilateral lung wa s 37.9 % for 3DCRT and 22.4 % (p<0.01)for IMRT,
whereas the V 20Gyof total lung (ipsilateral + contralateral) was 21.8% for 3DCRT and 12.14 (p <0.01) for IMRT. Similarly, ave r-
ageV40Gyof heart was 7.5 % for 3DCRT and 2.13 % (p =0.01) for IMRT. TheLAD maximum dose to left side breast patients , on
average, was 39.5 Gyfor 3DCRT and 29.17 Gy (p =0.03) for IMRT. The average number of m onitor unit swas about 180 for
3DCRT and 1441 (p<0.01) for IMRT. Conclusion: IMRT for breast cancer treatment is feasible. In comparison to 3DCRT,
IMRT can reduce the maximum dose to the target volume, and dose to theOAR. However, 3DCRT technique is superior in
terms of low dose volume, integral dose, and treatment time. With the use of breath -hold gated technique in IMRT, it can fu r-
ther improve the target coverage and reduction of doses to the heart, lung, and LAD. SIBtechnique could reduce the overall
treatment duration by about one week.
Keywords: Intensity Modulated Radiation Therapy , Three Dimensional Conformal Radiotherapy, Simultaneous Inte grated
Boost, Breat h-Hold, Technique, Breast Cancer
Introduction
Breast cancer is the most common malignancy in women.
Radiotherapy is an integral part of breast cancer man age-
ment either in breast conservation surgery (BCS) or in postmastectomy cases. Many prospective studies have shown
that adjuvant radiotherapy improves local control and sur-
vival rate in breast cancer patients after surgery.1During
earlier days of radiotherapy, opposed wedged fields with half
beam block was considered as the standard radiation therapy
technique. In the last decade , an introduction of linear a c-
celerators has made 3 -dimensional conformal radiotherapy
(3DCRT) as a standard treatment technique, which can
re-duce the doses to the lung, heart, and other critical stru c-
ture doses in the breast cancer treatment. However, using
3DCRT, it is not always possible to achieve adequate normal
tissue sparing, especially when t reating left side chest wall
patients. This is mainly due to overlying concave shape ofCorresponding author: Suresh Moorthy , M.Sc, M.Phil ; Division of
Radiation Oncology, Department of Oncology & Hematology,
Salmaniya Medical C omplex, MOH, Kingdom of Bahrain .
Email:nmsureshm@gmail.com
Cite this article as :Moorthy S, Sakr H, Hasan S, Samuel J,
Al-Janahi S, Murthy N .Dosimetric study of SIB-IMRT versus
SIB-3DCRT for breast cancer with breath -hold gated technique .
Int JCancer Ther Oncol 2013;1(1):010110 .
DOI:10.14319/ijcto.0101.1 0Dosimetric study of SIB-IMRT versus SIB-3DCRT for
breast cancer with breath-hold gated technique

Moorthyet al.:SIB-IMRT vs. SIB -3DCRT for breast cancer International Journal of Cancer Therapy and Oncology
www.ijcto.org
Copyright ©Moorthy et al. ISSN 2330 -40492
the target, which can result more doses to adjacent structures
such as heart and lung. Hong et al.2compared intensity
modulated radiation therapy (IMRT) with 3D confo rmal
tangential wedged beams, and showed the reduction of dose
to the coronary arteries, contra lateral breast, ipsilateral lung,
and surrounding soft tissues using IMRT. By modulating
photon beam, it is possible to obtain concave and convex
shape dose dis tributions with IMRT, and it has the ability to
conform radiation dose to irregular target volumes sparing
the underlying critical structures resulting in better tumor
control probability (TCP) and reduced normal tissue co m-
plication probability (NTCP). The main purpose of this study
was to further evaluate normal tissue sparing and dosimetric
analysis of simultaneous integrated boost (SIB) -3DCRT and
SIB-IMRT in breastpatients, with focus on breath -hold gat-
ed technique.
Materials and Methods
In this retr ospective treatment planning study, we used
computed tomography (CT) data of 36 consecutive patients
with breast cancer post lumpectomy (18 left sides and 18
right sides), and all patients were treated with respiratory
gated technique for breast radiothera py.
CT Simulation
All 36 patients were simulated using 4D CT scanner (Philips
Medical Systems, Andover, MA, USA) with whole -body
Vaclok (Civco Medical Solutions, Iowa, USA) immobilization
system. Patients were positioned on a wide bore CT -SIM
couch with t he help of lasers, and both arms of the patient
were raised above patient’s head. Furthermore, radio opaque
markers were placed during the immobilization procedure to
guide the isocenter shift. For all the patients, CT scans ima g-
es were obtained from mandi ble to upper abdomen area with
intravenous contrast, and CT scans were obtained using slice
thickness of 5 mm. Prior to CT simulation, patients were
given training on breath -hold technique.
Target Delineation and Dose Prescription
After the CT simulatio n, the Digital Imaging and Commun i-
cations in Medicine (DICOM) images were transferred to
Eclipse treatment planning system (TPS) (version 10.0.34,
Varian Medical Systems, Palo Alto, California, USA). Clinical
target volume (CTV), planning target volume (PT V) and
Organ at Risk (OAR) volumes were delineated on th e axial
CT slices. The lumpecto my gross tumor volume (L -GTV) was
contoured using all available clinical and radiographic i n-
formation including the excision cavity volume, architectu r-
al distortion, lum pectomy scar, seroma and/or extent of su r-
gical clips.
CTV1 included the palpable breast tissue demarcated with
radio opaque markers at CT simulation. The apparent CT
glandular breast tissue visualized by CT, consensus defin i-
tions of anatomical borders, a nd the lumpectomy CTV fromthe RTOG breast cancer atlas. The breast CTV is limited
anteriorly within 3 mm from the skin and posteriorly to the
anterior surface of the pectoralis, serratous anterior muscle
excluding chest wall. PTV was created by 3D expansi on of
CTV1 by 7 mm. CTV2 was createdby 1 cm 3D expansion
from L-GTV and was limited posteriorly at anterior surface
of the pectoralis and antero -laterally 3 mm from skin. PTV2
was created by 7 mm 3D expansion of CTV2. The normal
structures were contoured as ipsilateral lung, contra lateral
lung, contra lateral breast, heart, left anterior descending
(LAD) artery, spinal cord, esophagus, trachea, h umerus head,
and liver. Dose prescription was applied per International
Commission on Radiological Units and Measurements
(ICRU) 50 and 62.3, 4Specifically, dose was prescribed as 45
Gy in 25 fractions (1.8Gy/fraction) to the PTV -1 and 60 Gy
in 25 fractio ns (2.4Gy/fraction) to PTV -2.
Treatment p lanning
For treatment planning, 6mega-voltage ( MV)X-rays from
Clinac 600CD linear accelerator (Varian Medical Systems,
Palo Alto, California, USA) integrated with 120 leaves mi l-
lennium multi-leaf collimator ( MLC)was used .For thedy-
namicIMRT plans ,7 non-coplanar beams were used to
achieve the minimum criter ia of 95% of the volume received
95% of the prescribed dose. The treatment fields werealmost
evenly spaced within an arc of 1800on the side of the tumor.
Gantry angles ranged from 3300to1500(clockwise) for the
left sidetumorsand from 500to 2100(counterclockwise) for
theright side tumors. In Eclipse TPS, the IMRT plans were
created with inverse plan optimization ,and the algorithm
used was Dose Volum e Optimizer (version 10.0.28). For the
dose calculation , pencilbeamconvolution (PBC) algorithm
(version 10.0.28) was used ,and leaf motions were calculated
withleafmotioncalculator (LMC) algorithm (v ersion
10.0.28).Heterogeneity correction was done using modified
Batho method in the Eclipse.For plan optimization, OAR
dose constraints were given as ipsilateral lung V 20< 30 %,
heart V 30, V40, and mean dose as low as possible, co n-
tra-lateral breast mean dose less tha n 5 Gy, and spinal cord
maximum point dose less than 40 Gy. For the 3DCRT
plans, 4 to 6 non -coplanar beams were used to produce ad e-
quate dose coverage for thePTV. Critical organs were
shielded using MLC without compromising PTV coverage.
Beam weights wer e adjusted until the optimum coverage and
acceptable hot spots were achieved. Additionally,
field-in-fieldwas created to reduce hotspot equal toorlower
than110%as well as to improve the target coverage and
homogenous dose distribution in thePTV.
Plan evaluation
Dose-Volume Histograms (DVH) was used to analyze the
volume receiving 20 Gy, 30Gy and 40 Gy, mean, maximum
and minimum doses. The target dose uniformity and co n-
formity were calculated and evaluated. Different scoring
indices were given by various authors .5-7Inthis study, we
have followed indices defined by ICRU 83.8

Volume 1 • Number 1• 2013 International Journal of Cancer Therapy and Oncology
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Copyright ©Moorthyet al. ISSN 2330 -40493
The conformity index (CI) as defined in ICRU 83is
refVolume of PTV covered by the reference d ose
CI = Eq. 1
Volume of PTV
CI = 1.0 is ideal value
The Homogeneity Index (HI) as defined in ICRU 83is
2% 98%
50%Eq. 2D D
HI
D

Where, D 2%, D98%,D50%is dose received by 2%, 98%, 50%
volume. HI = 0 (Zero) is ideal value .Also,to illustrate the
low dose volume effect, V 5Gyvolume and integral dose were
calculated for normal healthy tissue.
Integral Dose = Mean Dose (Gy) ×Volume (Cm3)Eq. 3
Statistical Analysis
Statistical Analysis was performed using the Wilcoxon
Signed Rank test. This matched pair t test was applied to
determine the statistical difference between the
dose–volume data for IMRT versus 3DCRT. The values are
reported in ranges. The reported p value is two tailed, and p
values of < 0.05 are considered statistically significant.
Results and Discussion
Dose volume histograms of the normal tissues of both the
plans (IMRT and 3DCRT )are presented in Table 1.The
normalized target coverage of both treatment methods is
presented in Table 2 and Table 4 .The PTV mean dose for
3DCRT is 47.1 0Gy compared to 45.88 Gy (p <0.01) with
IMRT. The dose distribution in axial sections is shown in
Figures 1 and 2 .These axial sections clearly show that con-
cave PTV coverage and exclusion of LAD during optimiz a-tion byIMRT. Also ,previous studies have reported lower
doses to the ipsilateral lung, contra lateral lung, contra lateral
breast, heart ,and LAD doses usingIMRT technique .10, 11
3D conformal plans using asymmetric jaw and field -in-field
technique provides bett er coverage than a conventional
physical wedged –half beam blocked or physical
wedged-asymmetric fields. Furthermore, physical wedge has
limitation in field width and lengths. With 3DCRT, the hot
spots occurred in superficial skin surface, but IMRT exhibi t-
ed better control in shifting the hot spots, with a possibility
of keeping dose to the skin equal to or less than the prescri p-
tion dose.
Dose homogeneity and conformity
The use of equally spaced gantry angles improved homog e-
neity and conformity indices as well as reduced the volume
of critical normal tissues such as the heart and ipsilateral
lung receiving a high dose as shown by Hong et al.2. In this
study, we used equally spaced beam angles for both the
IMRT and 3DCRT plan s, and the average target maximum
dose was lower with IMRT; however, it was not statistically
significant. Although t he mean breast volume in our study
was 1221 cc, which is relatively higher compared to the li t-
erature12, we were able to demonstrate optim ized coverage
and reduced dose to the critical organs.
The inverse -planning IMRT further reduced hotspots mainly
due to beam modulation during optimization compared to
3DCRT, where beam modulation is not available. Previous
planning studies13,14with mul tiple fields showed the
PTV-95% coverage values ranging from 90% to 97 %,
whereas all our optimized plans had the PTV -95% coverage
values of >95% of prescription dose. With the use of IMRT
technique, our data showed that there is a consistent i m-
provement i n conformity index from 0.18for 3DCRT to 0.15
for IMRT (p=0.01). However, there was no significant di f-
ference (p = 0.45) when HI of 3DCRT was compared to that
of IMRT.
TABLE1:Comparison of normal tissue dose volume parameters for
Respiratory Gated IMRT and 3DCRT breast cancer patients (Stati s-
tics based on Wilcoxon Signed Rank Test) . The values are averaged
over 36 analyzed patients.
Organ Parameter SIB-3DCRT SIB-IMRT
Ipsilateral lungV20Gy (%) 37.9 22.4
V30Gy(%) 32.24 16.08
Mean (Gy) 20.29 16.51
Heart V40Gy (%) 7.5 2.13
Both Lung V20Gy(%) 21.8 12.14
LAD Max. Dose (Gy) 39.5 29.17TABLE2:Comparison of planning target volume (PTV1) coverage
parameter for Respiratory Gated IMRT and 3DCRT breast can cer
patients (Statistics based on Wilcoxon Signed Rank Test) .The values
are averaged over 36 analyzed patients.
PTV 1 Parameter SIB-3DCRT SIB-IMRT p
Minimum Dose (Gy) 24.07 32.03 <0.01
Maximum Dose (Gy) 51.97 59.68 <0.01
Coverage (%) 96.8 98.22 <0.01
Conformity Index 0.18 0.14 0.01
Homogeneity Index 1.03 1.01 0.45
Mean Dose (Gy) 47.1 45.88 <0.01
Mod Dose (Gy) 49.12 48.92 0.32
Median Dose (Gy) 50.5 48.8 <0.01
Stnd. Deviation(Gy) 6.35 4.17 <0.01
V50Gy(%) 48.69 29.83 <0.01
V55Gy(%) 30.7 11.29 <0.01

International Journal of Cancer Therapy and Oncology
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Copyright ©Moorthyet al. ISSN 2330 -4049FIG.1: Axial slice showing dose distribution in 3DCRT plan. The
3DCRT was unable to exclude LAD while covering the concave
target, and increased dose to theheart and lung was noticed.
TABLE3:Comparison o f MU, ID and V5 parameter for Respiratory
Gated IMRT and 3DCRT breast cancer patients (Statistics based on
Wilcoxon Signed Rank Test) . The values are averaged over 36 an a-
lyzed patients.
Parameter SIB-3DCRT SIB-IMRT p
Monitor Units 180 1441 <0.01
Integral Dose ( Gy-Cm3)145210 197428 <0.01
V5Gy(%) 18.89 30.61 <0.01
TABLE 4 :Comparison of planning t arget volume (PTV2) coverage
parameter for Respiratory Gated IMRT and 3DCRT breast cancer
patients(Statistics based on Wilcoxon Signed Rank Test) . The values
are averaged over 36 analyzed patients.
PTV 2Parameter SIB-3DCRT SIB-IMRT p
Minimum Dose (Gy) 56.41 53.9 <0.01
Maximum Dose (Gy) 64.9 64.01 <0.01
Coverage (%) 98.3 99.77 0.13
Conformity Index 0.12 0.08 0.01
Homogeneity Index 1.02 1.01 0.11
Mean Dose (Gy) 61.1 61.72 0.13
Mod Dose (Gy) 61.17 62.13 <0.01
Median Dose (Gy) 61.99 62.45 <0.01
Stnd. Deviation(Gy) 1.5 1.21 0.01
TABLE 5 :Comparison of Non-Gated IMRT with r espiratory Gated
IMRT (mean) breast cancer patients (Statistics based on Wilcoxon
Signed Rank Test) .The values are averaged over 36 analyzed patients.
Parameters Non-Gated
SIB-IMRTGated
SIB-IMRTp
LAD-Maximum Dose 35.62Gy29.17Gy<0.01
Heart-V30Gy 9.27 % 5.91 % <0.01
Ipsilateral Lung -V20Gy 30.2 % 22.4 % 0.03
PTV-95% of prescription 96.81% 98.22 % <0.01
In patients with breast cancer, it is intended that the irrad i-
ated heart volume be minimized to the greatest possible d e-
gree without compromising the target coverage. The risk of
pericardial events is probably related to both dose and vol -FIG.2:Axial slice showing dose distribution in IMRTplan. The
IMRT was able to exclude LAD while covering the concave target,
anddecreased dose totheheart and lung was noticed.
ume of radiation. The incidences of pericardial disease d e-
crease with th e use of sub cranialblocking the major ventr i-
cles at 30 Gy. Stewart et al.15concluded that the dose should
be limited to 60 Gy for less than 25% of cardiac volume and
45 Gy for more than 65% of cardiac volume.
In patients with breast cancer, it is inte nded that the irrad i-
ated heart volume be minimized to the greatest possible d e-
gree without compromising the target coverage. The risk of
pericardial events is probably related to both dose and vo l-
ume of radiation. The incidences of pericardial disease d e-
crease with the use of sub cranialblocking the major ventr i-
cles at 30 Gy. Stewart et al.15concluded that the dose should
be limited to 60 Gy for less than 25% of cardiac volume and
45 Gy for more than 65% of cardiac volume .
In our study the heart V 40Gywas significantly lower in IMRT
than in 3DCRT (p <0.01), especially for left sided breast
cancer patients, with mean heart V 40 Gyof 7.5% for 3DCRT
versus IMRT as 2.13% (p =0.01). Gagliardi et al.16reported
that CAD risk was much reduced at doses less than 30 Gy.
Mean values of V 30Gywere <5% for IMRT compared with
studies17reporting V 30Gyvalues in the range of 2% to 5%.
Increased cardiac mortality risk associated with left side
breast patients in the long term was reported by multiple
authors.16, 18,19The advancement in treatment techniques
such as IMRT has enabled to reduce cardiac exposure, and
steady decline of radiation risk is being noticed.20Further-
more, Boivin et al.21noted that the anteriorly placed cor o-
nary arteries were more often affect ed by radiation therapy
(compared with the circumflex artery). In our study, mean
LAD maximum dose was 39.5 Gy for 3DCRT and 29.17 Gy
for IMRT (p =0.03).
Lung dose
The occurrence of r adiation pneumonitis (RP) isrelated to
the ipsilateral lung volume irradiated .22In our study ,the
ipsilateral lung V 20Gyfor IMRT (22.4%) is significantly less
thanthatfor 3DCRT (37.9%; p <0.01). Ipsilateral lung mean
dosewasalso higher in 3DCRT (20.29 Gy) compared to the
one inIMRT (16.51Gy) (p <0.01).Boththelung V 20Gyand

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Copyright ©Moorthyet al. ISSN 2330 -40495
mean dose weresignificantly lower in IMRT than in3DCRT
(p<0.01).Contra lateral lung V 5Gyand mean dose of both
the plans show edno significant differences. The mean lung
doses(MLD)of both lung werehigher compared to the r e-
port from M arkset al.23, and this may be due to larger breast
volumes in our study. Since there is no absolute safe MLD
below which there is no pneumonit is, the clinically accept a-
ble risk of RP depends on the risk -benefit ratio of the ind i-
vidual patient selection basis.
Secondarymalignancy
The IMRT plans contributed a modestly higher dose to adj a-
cent healthy soft tissues. In our study , the mean V 5Gyvolume
for3DCRT wa s much lower than that of IMRT . The main
concern with healthy tissue dose increases of this magnitude
is an increased risk of late second malignancy .24, 25Some in-
vestigators suggest that IMRT might increase the incidence
of secondary cancer from 1% in conventional planning to
1.75% in IMRT planning for patient’s surviving 10 years.24
Furthermor e, the treatment Monitor Unit (MU) wa s signifi-
cantly higher in IMRT technique. The monitor unit for
IMRT is 6 -8 times more than 3DCRT is a concern .24, 26, 27This
in turn shows that the integral dose would be higher.
Pirzkallet al.28studied that the i ntegral dose for IMRT wa s
higher than conventional treatment. Similar observation was
made in our study as integral dose for IMRT was 22% higher
thanthat for3DCRT.This higher integral dose wasprobably
due toincreased number of beamsused in IMRT than in3D
CRT, thus involving largervolume of healthy tissue during
IMRT plan optimization. Modulation of beams also increases
thetreatment time during treatment delivery. Furthermore ,
theleakage and scatter dose to non -target tissue of the p a-
tients will be proportional to the number of mon itor units
used. Few studies13, 29have found to have increased low dose
volumes with increasing beam angles .
High integral dose attributed to second malignancy ,which is
likely to be of greatest concern in younger women and in
patients with a low risk for systemic relapse that are likely to
live for many years after the diagnosis of breast cancer .27
There have been reports24suggesting that adjuvant radiation
therapyfor breast cancer may increase the risk of lung ca n-
cer and angiosarcoma. The risk of sarcoma in the treated
volume is likely to be similar with IMRT or standard tec h-
niques, but it is possible that second primary lung cancers
might be increased by IMRT , especially if the woman is a
smoker.27Therefore, individual assessment of treatment
volume goals and longevity of patients with and without
radiation therapy is necessary in order to balance the short
to medium -term benefits of reducing the volume of cr itical
structures, especially heart and lung, receiving higher radi a-
tion dose.
Respiratory gating
Organ motion during the IMRT treatment has been a c-
counted for using real -time position management (RPM ;VarianMedical System , Palo Alto, California, USA).The
RPMsystem supports automatic on and off triggering of r a-
diation beam during the treatment . The marker position
approximates identical and in -phase alignment of breast and
marker motion. Due to breathing motion, the PTV may
move outside the external co ntour as defined on the pla n-
ning CT and result in a geo graphic miss of the target. Alt-
houghthe geometric uncertainties and intra fraction mov e-
mentaretaken into account on PTV margin ,but the breast
is a superficial organ and often the CTV will extend to the
skin surface. In these cases, the restriction of the PTV to 3
mm from the skin surface will not provide an adequate ma r-
gin for intra -fraction breathing motion .29-33Themain con-
cern would be the CTV being under -dosed. In order to use
gating, the PTV m otion must be in phase with the breathing
cycle or must at least be able to be predicted from the
breathing cycle using technology such as RPM. Conformal
blocking and breath -hold techniques can essentially elim i-
nate the heart from the primary beams. Histor ically, whole
heart doses up to 30 Gy were reasonably well tolerated .34-36
Conclusion
IMRT for breast cancer treatment is feasible. Incomparison
to 3DCRT, IMRT reducedthe maximum dose tothetarget
volume, and dose to OAR wasreduced too.However,
3DCRT technique wa s superior in terms of low dose volume
of normal tissue ,integral dose ,and treatment time. Cons e-
quences of these low doses would have to be weighed against
the benefits of reducing high doses on individual patient
selection basis. With the use of breath -hold gated technique
in IMRT, it can further improve the target coverage and
reduction of doses to the heart, lung, and LAD. SIB tec h-
nique could reduce the overall treatment duration by about
one week.
Competing interests
The authors declare that they have no conflicts of interest.
The authors alone are responsible for the content and wri t-
ing of the paper.
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