Accepted Manuscript

Title: Evaluation of 3D-CRT, IMRT and VMAT radiotherapy

plans for left breast cancer based on clinical dosimetric study

Author: Haiyun Liu Xinde Chen Zhijian He Jun Li

PII: S0895-6111(16)30098-2
DOI: http://dx.doi.org/doi:10.1016/j.compmedimag.2016.10.001
Reference: CMIG 1476

To appear in: Computerized Medical Imaging and Graphics

Received date: 15-6-2016

Revised date: 20-9-2016
Accepted date: 10-10-2016

Please cite this article as: Liu Haiyun, Chen Xinde, He Zhijian, Li Jun.Evaluation
of 3D-CRT, IMRT and VMAT radiotherapy plans for left breast cancer
based on clinical dosimetric study.Computerized Medical Imaging and Graphics
http://dx.doi.org/10.1016/j.compmedimag.2016.10.001

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 Evaluation of 3D-CRT, IMRT and VMAT radiotherapy plans for
left breast cancer based on clinical dosimetric study

Haiyun Liu1,*, Xinde Chen2*, Zhijian He2,†, and Jun Li3

1.
Jiangxi University of Traditional Chinese Medicine, Nanchang, 330029, Jiangxi, China;
2.
Tumor Hospital of Jiangxi Province, Nanchang, 330029, Jiangxi, China;
3.
Jiangsu Subei People's Hospital, Yangzhou, 225001, Jiangsu, China.

†
Corresponding author
Zhijian He
Postal Address: Tumor Hospital of Jiangxi Province, Nanchang, 330029, Jiangxi, China.
Email：zhijianhe33@sina.com
*These authors contributed equally to the manuscript.
Highlights for review
1. This paper aims to compare dosimetric difference based on three types of radiotherapy
plans (3D-CRT, dIMRT and RapidArc) for postoperative left breast cancer.
2. Dose volume histogram has been used to analyze each evaluation index of clinical
target (CTV), organs at risk (OARs).
3. We showed that the target area of dIMRT and RapidArc plans has better conformity,
and that the RapidArc plan takes the advantages of less total MU quantity and total
treatment time.
Abstract
Objective: This paper aims to compare dosimetric differences based on three types of
radiotherapy plans for postoperative left breast cancer. In particular, based on a clinical
dosimetric study, the three-dimensional conformal radiotherapy (3D-CRT), intensity-
modulated radiation therapy (IMRT) and VMAT plans were implemented on 15 cases of
postoperative patients with left breast cancer with prescription doses of 5000 cGy. Methods
and Results: Dose volume histogram (DVH) was used to analyze each evaluation index of
clinical target volume (CTV) and organs at risk (OARs). Except for homogeneous index (HI),
D2, each CTV evaluation index of 3D-CRT plan was inferior to IMRT and VMAT plans
(P<0.05). Compared with the VMAT plans, IMRT has a statistical significance only in Dmean,
V95 (P<0.05). On the contrary, Dmean pertaining to the VMAT plan is much closer to the
prescription dose with a V95 coverage rate as high as 97.44 %. For the infected lung, V5, V10
of 3D-CRT were the lowest (P<0.05), while V20, V30 were the highest (P<0.05) among the
three types of plans. Here, the V5, V10 of infected lung were slightly higher (P<0.05) for the
VMAT and IMRT plans. Each evaluation index of the contralateral lung and heart in 3D-CRT
was the lowest (P<0.05). D1 of contralateral breast was lower in both IMRT and VMAT
plans, which were 1770.89±121.16 cGy and 1839.92±92.77 cGy, respectively. While D1 of
the spinal cord in IMRT and VMAT plans was higher, which were 1990.12±61.52 cGy and
1927.38±43.67 cGy, respectively. When the radiation dose of 500-1500 cGy was delivered
to the normal tissues, 3D-CRT significantly shows the lowest volume, VMAT is relatively
higher. Monitor Units (MU) and treatment time (T) of VMAT were the least, only 49.33%
and 55.86% of those of IMRT. Conclusion: The three types of plans can meet the clinical
dosimetry demands of postoperative radiotherapy for left breast cancer. The target of IMRT
and VMAT plans has a better conformity, and the VMAT plan takes the advantages of less
MU and treatment time.

Key words: Left breast cancer; 3D-CRT; IMRT; VMAT; Dosimetry.

1. Introduction
Radiation therapy has become one of the vital measurements of postoperative breast
cancer treatment. It is also the most important means of improving the local control rate of
tumor, as well as to reduce complication of the normal tissues. The scope of radiotherapy
covers mainly the chest wall and lymph nodes at positions above and under the collar bone.
The radiotherapy technology is more complex, and in order to avoid overlap and omission of
adjacent radiation, reducing radiation damage to normal tissue without missing the target area
ought to be taken as a basic requirement for radiotherapy[1].
Conventionally, the 3D-CRT has been one of the typical main plan solutions. Our
methods are based on breast tangential field irradiation and lymphatic draining region
irradiation by using center irradiation method of 1/4 tangent field and semi field. However,
this comes with the disadvantages of poor target area fitness and higher complexity in our
radiotherapy practice. In addition, IMRT being used for patients with post-operative breast
cancer has become more and more common. However, because of the complexity of the
design of treatment plan, the field angle also has important effects on the quality of treatment
plan[2]. And the extensive treatment time would cause reduction of relative biological effects,
postural changes of patients during treatment, decrease of treatment accuracy and a series of
problems.
With the rapid development of hardware and software in the field of radiotherapy, a
new type of technology known as the Volumetric Modulated Arc Therapy (VMAT), which
combines the fixed field IMRT and pull arc irradiation, has been developed recently.
Dosimetry studies show that VMAT can be better than the fixed field IMRT. The VMAT
technology that is provided by Varian Eclipse 8.6 planning system has already been confirmed
as VMAT mode by Otto, etc [3]. To achieve rotation IMRT treatment, this technology was use
to calculate the state of multi-leaf collimator motion by adopting reverse optimization
algorithm, meanwhile by optimizing the dose rate and rotate speed of the rack. Due to the arc
structure of the breast cancer, three radiotherapy techniques, i.e., 3D-CRT, IMRT and VMAT,
have been widely applied in clinic nowadays. The purpose of this paper was to compare the
dosimetric parameters and to obtain the most superior radiotherapy technique, i.e., to obtain
the optimal dosimetric distribution of the target and to maximum reduce the dose delivered to
the lung by designing three radiotherapy plans for a certain case.

2. Materials and Methods

2.1 Case Selection: We randomly selected 15 cases of postoperative radiotherapy for breast
cancer in our hospital during March 2011 and March 2013. The patients are all female, aged
38 to 65 years old, the average age of 45 years old, and the primary lesions are left breast.

2.2 CT simulation location and target area delineation and definition: patients raised both
arms above their heads, and were fixed by the vacuum negative pressure bag. CT scans with a
slice thickness of 5mm were obtained using large aperture 16 rows spiral CT of GE Medical
Systems. CT scans ranges from the mandible to the thorax, which completely cover all the
adjacent normal tissues and organs such as lung, heart, opposite breast and the spinal cord, etc.
The clinical target volume (CTV), including the whole ipsilateral chest wall and lymph node
region around collar bone, was outlined by the oncologist by using Varian eclipse 8.6
treatment planning system (TPS), and the organs at risk (OARs) including ipsilateral lung,
contralateral lung, contralateral breast, heart, and the spinal cord were delineated then.

2.3 Plan design: The prescription dose given was 5000cGy, which was irradiated for 25
times, herein, for fractionated dose of 200cGy, 99% of CTV is supposed to receive at least
95% of prescription dose (4750cGy). Clinical constraints are as follows: CTV≤107%, the
minimum dose≥95%, V20<30% and the average dose Dmean<1500 cGy for the ipsilateral lung,
the maximum dose of the spinal cord Dmax<4000 cGy, V40<50% for heart and the dose
delivered to the contralateral lung and the contralateral breast should be less as far as possible.
The three radiotherapy plans are as follows:
(a) 3D-CRT: using 6 MV X-ray, chest wall using 1/4 tangential field, lymphatic drainage
area around collar bone using isocenter semi field irradiation. Avoid shoot omitting and
dosage overlapping. And algorithm model is Anisotropic Analytical Algorithm (AAA).
(b) IMRT: using 6 MV X-ray, 5 fields isocenter way (130°, 95°, 0°, 330°, 290°) to do the
reversal dynamic optimization design. And algorithm model is AAA.
(c) VMAT: using 6 MV X-ray, double arc way (clockwise and counterclockwise) to
disperse field, abduction of 10°-25° by tangent field as starting and ending angle each way,
with collimator angle 5°, treatment couch angle 0°, maximum dose rate 600 MU/min, and
algorithm model is AAA. In the process of designing, doses of cold and hot points were
optimized and adjusted by defining dose shaping structure (DSS) [3] .

2.4 Plan assessment: (a) We aim to evaluate the parameters including Dmean, D2, D98, V90,
V95 , CI and HI for CTV. Herein, CI [4, 5] is expressed by
Vt , ref Vt , ref
CI   , (1)
Vt Vref

where Vt stands for the target volume, Vt,ref stands for the target volume surrounded by
reference isodose surface, Vref is the volume of all areas surrounded by reference isodose
surface. Here, CI ranges from 0 to 1, and higher CI values indicate better conformity. HI [5] is
given by
D2  D98
HI   100 0 0 , (2)
D prescription
where D2 and D98 (dose received by the 2% and 98% of the volume, respectively) are metrics
for minimum and maximum doses. Dprescription is the prescription dose, and lower HI values
indicate superior dose homogeneity of the target volume.
(b) Clinical constraints for OARs: V5, V10, V20, V30 and Dmean for the infected lung;
Dmean,V5 and V10 for the contralateral lung; Dmean and D1 for the contralateral breast; Dmean and
V10 for the heart; D1 for the spinal cord.
All the data in this article utilized the SPSS15.0 for statistical analysis. We adopted the
paired-samples T-test to perform the comparison of dosimetry differences among 3 plans,
which is based on as the statistical difference (P<0.05).
3. Results
The following results are based on our experimentations:
3.1 Distribution of the Target Dose: As shown in Table 1, except for HI, D2, all the
evaluation parameters for CTV in 3D-CRT plan were inferior to those in IMRT and VMAT
plans (P<0.05). However, CI was lowest in 3D-CRT plan and also reflected in Figure 1.
Compared with VMAT plans, IMRT had a statistical significance only for Dmean, V95. Then,
Dmean was much closer to the prescription dose, and V95 reached to 97.44 % in VMAT plan.

3.2 Comparison of OARs Dosimetry: The results of OARs were shown in Table 1. For the
ipsilateral lung, V5, V10 in 3D-CRT were the lowest (P<0.05), while V20, V30 were the highest
among three kinds of plans. V5, V10 of the infected lung were slightly higher in VMAT and
IMRT. Each evaluation index of the contralateral lung and heart in 3D-CRT were the lowest.
D1 of the contralateral breast were lower in IMRT and VMAT plans, which were
1770.89±121.16 cGy and 1839.92±92.77 cGy, respectively. While D1% for the spinal cord in
IMRT and VMAT plans were higher, which were 1990.12±61.52 cGy and 1927.38±43.67
cGy, respectively.

Table 1. Dosimetric Parameters Comparison of CTV and OARs in three Plans

Project 3D-CRT IMRT VMAT P value
CTV
HI 1.12±0.11 1.10±0.09 1.10±0.10 —
CI 0.33±0.08 0.77±0.05 0.79±0.05 a,b
Dmean(cGy) 4944.03±92.30 5139.32±56.32 5051.09±61.91 a,b,c
D2%(cGy) 5299.38±51.82 5455.51±39.11 5358.88±44.63 —
D98(cGy) 4518.21±103.40 4753.62±66.23 4768.93±63.47 a,b
V90(%) 98.24±0.51 99.28±0.72 99.29±0.37 a,b
V95(%) 90.22±1.20 96.05±0.77 97.44±1.21 a,b,c
Infected lung
Dmean(cGy) 1385.14±110.34 1353.21±98.43 1378.37±83.42 —

V5(%) 41.67±4.20 72.36±5.71 76.53±4.29 a,b,c

V10(%) 35.58±3.37 41.99±3.01 45.02±2.74 a,b,c
V20(%) 29.45±2.46 24.46±2.05 25.41±1.98 a,b
V30(%) 28.14±1.34 15.95±1.27 16.17±0.88 a,b
Contralateral lung
Dmean(cGy) 107.77±18.23 466.22±34.45 532.18±42.31 a,b,c
V5(%) 2.08±0.31 35.89±2.55 37.47±2.45 a,b
V10(%) 0.92±0.14 11.85±1.34 10.58±1.57 a,b
Contralateral breast
 Dmean(cGy) 624.71±50.96 667.57±64.81 844.65±57.29 a,b,c
D1(cGy) 3934.77±301.47 1770.89±121.16 1839.92±92.77 a,b
heart
Dmean(cGy) 881.53±51.56 1302.42±67.22 1367.39±61.64 a,b

V10(%) 20.11±1.45 46.94±2.06 45.27±2.31 a,b

V5(%) 15.58±1.82 17.55±1.49 18.94±1.23 a,b
Spinal cord
D1(cGy) 807.92±145.57 1990.12±61.52 1927.38±43.67 a,b
Notes：a=3D-CRT vs. IMRT; b=3D-CRT vs. VMAT; c= IMRT vs. VMAT

Fig. 1. The three dose distribution of the cases based on one patient sample.

3.3 Normal Tissues Comparison: As shown in Figure 2, in the range of 500-1500 cGy, the
normal tissue volume was lowest in 3D-CRT plan, while the volume was highest in VMAT
plans; the volumes in three plans were similar in V20, and the volumes in IMRT and VMAT
plans become similar starting from 1500 cGy; compared with the other two plans, the volume
in 3D-CRT plan was highest at the point of 3000 cGy.
 Fig. 2. The histogram of low dose area of the normal tissue in three radiotherapy plans.
3.4 MU and Treatment Time Comparison: The average MU were 496±27, 827±31 and
408±16, respectively in 3D-CRT, IMRT and VMAT plans. MU in VMAT plan was 50.67%
of that in IMRT. Moreover, the treatment time were 172s, 213s, and 119s, respectively.
However, the treatment time in VMAT plan was 94 seconds less than that in IMRT plan,
which remarkably having improved the utilization of X-rays.

4. Discussion
VMAT is a kind of Rotational Intensity Modulated technology based on VMAT theory
proposed by Otto[3]. The full arc frame can rotate about 360°. The arc consists of 177 control
nodes, whereby the rotating speed of the frame is 4.8°/s. The maximum dose rate is 600
MU/min. MLC blade’s maximum speed is 2.5 cm/s. Gantry rotation takes about 75 s per
circle. Many scholars have done researches on VMAT in the body, the head and the neck. The
results show that VMAT can reduce the total time of radiotherapy plan for patients and the
beam-on time of the accelerator. The greatest advantage of VMAT technology is to further
reduce the treatment time and the number of MU without reducing dose distribution, so as to
improve the treatment target of biological effects and the number of patients treated in a unit
of time[6-9]. Because the number of MU reduces obviously, thereby reducing the number of
scattering lines of the accelerator head collimator, the risk of cancer reoccurrence is reduced
theoretically.
The study compares three kinds of radiotherapy techniques for left breast cancer. These
three treatments can meet the clinical requirements. The target area fitness and DVH of
3D-CRT were not so good as those of IMRT and VMAT, which may be related to the field
conditions of 3D-CRT. But the doses delivered to the spinal cord D1 and the infected lung
(including V5, V30) in 3D-CRT were the lowest. But the average dose Dmean, V20 and V30 were
higher compared with the other two plans. Furthermore, the average doses to contralateral
lung, contralateral breast and heart were the lowest while the high dose point was higher.
Because such field mode can maximally avoid the spinal cord, but lead to increasing the high
dose area and the average dose of ipsilateral lung. IMRT also has good dose distribution in
the target. It can reduce the maximum dose of the target area, and allow the average dose
Dmean of target area to be closer to the prescribed dose. The target area fitness and DVH can
meet the clinical needs. But its reception amount of the spinal cord D1 is higher than that in
3D-CRT and VMAT plans and the reception amount of ipsilateral lung (including V20, V30,
the average dose Dmean) is the lowest. But the V5 and V10 are between 3D-CRT and VMAT
plans. Also, the average doses to the contralateral lung, contralateral breast and the heart are
between 3D-CRT and VMAT plans. The target area fitness and DVH of VMAT are better
than the other two plans, and the reception amount of the spinal cord D1 is between the other
two plans. All indicators of ipsilateral lung were higher than that of other plans, and some
other indicators (Dmean, V5) of contralateral lung, contralateral breast and heart are higher than
the other plans. In addition, the indicator (V10) is better than the other plans. This study
showed that IMRT and VMAT has incomparable advantages than 3D-CRT plan in dose
distribution and uniformity. They can guarantee the treatment target to obtain sufficient dose,
reducing the cold and hot points of the dose in the target area. That can prevent tumor of chest
wall recurrence. For the high dose region volume of the normal tissue, IMRT and VMAT
plans are smaller, while 3D-CRT is larger; For the low dose region volume of normal tissue,
IMRT and VMAT plans are larger, and 3D-CRT plan is smaller. The reason of having larger
low dose volume of normal tissues in IMRT and VMAT plans may be the following: the
number of intensity modulated radiation field is more, field scattering radiation is more and
field passes through the normal tissue.
In general, the results shows that the ipsilateral lung V20 of the three plans are not
significantly different. VMAT plan can significantly reduce the high dose volume of the
ipsilateral lung (V30). But due to the increasing of scattered radiation, IMRT and VMAT plan
also significantly increase the low dose irradiated volume (V5, V10) compared to 3D-CRT
plan. VMAT plan has more average dose to the contralateral lung, contralateral breast and
heart than 3D-CRT plans. But we still cannot definitely tell the advantages and disadvantages
of the three plans on lung protection. The is because the DVH parameters can be related to the
radiation injury based on different angles. According to DVH data of the radiotherapy for
lung cancer patients, the risk of radiation pneumonitis is related to the average dose of lung
(MLD) and V20, V30 [10-12]. And V5, V10 are to the effective factors to estimate the
occurrence of radiation pneumonitis [13]. This paper demonstrates VMAT plan protects the
normal tissue of the affected side with good effect.
The results are also similar to the results by Qiu et al. [14], Shaitelman et al. [15], and
Sun et al.[16]. The three plans have not much difference for the heart. But for the spinal cord,
contralateral lung and contralateral breast, VMAT has no advantage. VMAT plan has
minimum number of monitor units MU and shortest treatment time. For left breast cancer
patients, 3D-CRT can meet the clinical requirements, but has no advantage in the protection
of normal breast tissue. VMAT plan has the advantages of protecting normal breast tissue,
and can obviously shorten the treatment time. And the influence of the movement during
treatment, organ changes caused by respiratory motion and involuntary movement will be
reduced accordingly. Patient’s discomfort and graded internal displacement are reduced.
Ultimately the accuracy of dose distribution and treatment effect are improved. Meanwhile, in
the process of designing and optimizing IMRT and VMAT Plans, it takes longer time than
that of 3D-CRT because the parameters are adjusted and optimized repeatedly. Especially in
the VMAT plan, the optimization process is divided into 5 steps, one by one completed. It not
only needs to optimize the sub field and weight, but also because of many physical parameters
in optimization plan, the optimization process is complex limited to the version of the system.
The time-consuming process can reduce our work efficiency considerably.

5. Conclusion
In our paper, we note that all of the three plans based on 3D-CRT, IMRT and VMAT
technology can achieve the basic requirements of clinical treatment, but in the process of
treatment there are many uncertain factors. Therefore we need to obtain an accurate target
volume delineation and strict control in order to assure a high quality. The dosimetric
parameters pertaining to the Rapid Arc and IMRT have certain advantages. In addition, they
have greatly increased the number of MU, the efficiency of treatment and time. But they need
to further reduce the amount of the subject in the contralateral lung, heart, spinal cord, and the
other organs.
Conflict of interest: The authors declared no conflict of interest.

Role of the funding source: This research is not funded.

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