Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT
1 Department of Radiotherapy, Krishna Institute
of Medical Sciences, Hyderabad, India
2 Department of Radiotherapy, National Oncology
Centre, The Royal Hospital, Muscat, Sultanate of Oman
Purpose: To assess the potential advantage of
intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT)
planning in postoperative adjuvant radiotherapy for patients with gastric
carcinoma. Methods and materials: In a retrospective study, for plan
comparison, dose distribution was recalculated in 15 patients treated with
3D-CRT on the contoured structures of same CT images using an IMRT technique.
3D-conformal plans with three fields and four-fields were compared with
seven-field dynamic IMRT plans. The different plans were compared by analyzing
the dose coverage of planning target volume using TV95, Dmean,
uniformity index, conformity index and homogeneity index parameters. To assess
critical organ sparing, Dmean, Dmax, dose to one-third
and two-third volumes of the OARs and percentage of volumes receiving more than
their tolerance doses were compared. Results: The average dose coverage
values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans
achieved better target coverage(p<0.001) with higher conformity index
value of 0.81�0.07 compared to both the 3D-CRT plans. The doses to the liver
and bowel reduced significantly (p<0.001) with IMRT plans compared to
other 3D-CRT plans. For all OARs the percentage of volumes receiving more than
their tolerance doses were reduced with the IMRT plans. Conclusion: This
study showed that a better target coverage and significant dose reduction to
OARs could be achieved with the IMRT plans. The IMRT can be preferred with
caution for organ motion. The authors are currently studying organ motion in
the upper abdomen to use IMRT for patient treatment. � 2010 Biomedical
Imaging and Intervention Journal. All rights reserved.
Keywords: Conformal radiotherapy, intensity modulated
radiotherapy, organs at risk, planned target volume, tolerance doses
Gastric cancer is the second most common cancer worldwide,
with a frequency that varies greatly across different geographic locations .
Despite the decreasing worldwide incidence, gastric cancer accounts for 3% to
10% of all cancer related deaths . In spite of technical advances
in surgery and adjuvant therapy, the mortality associated with gastric cancer
is prevailing. Patients with localized node negative gastric cancer have 5-year
survival rates that approach 75% when treated with surgery alone . This is
in contrast to patients with lymph node involvement, in whom survival rates
range from 10% to 30% [4, 5, 6]. Preliminary studies of adjuvant
chemo-radiotherapy showed promising results in patients resected with curative
intent [7, 8].
The target delineation as well as the treatment technique
of radiation dose delivery to the post operative stomach remains complex. This
is due to the large planned target volume (PTV) and surrounding mobile parts of
bowel and other critical organs, such as liver, kidneys and spinal cord. Recent
data indicate that post-operative chemo-radiotherapy improves clinical outcome
by improving the relapse-free survival in gastric cancer and that acute
toxicity is acceptable . Data on late side effects, however, are scarce.
Renal function impairment represents one of the most serious late complications
following abdominal radiotherapy.�������������
The CT images with 3-dimensional (3D) planning software
help in displaying the 3D-dose distribution at different levels in the PTV. In
conventional 3D-CRT for stomach cancer, very commonly three-field technique
(3F-CRT) or four-field technique (4F-CRT) is used. All the fields are shaped
with MLC and either physical or dynamic wedges are used to achieve optimal
three-dimensional dose distribution with minimal degree of dose inhomogeneity
through forward treatment planning. Early and late radiation induced complications
are directly related to the total dose delivered, fractionation scheme,
radiation treatment technique and patient anatomy. Several institutions have
reported the use of different techniques to improve the dose distribution
within the PTV [10-13].
Despite all efforts in the conventional method of
planning, the surrounding normal tissue of PTV and other critical organs at
risk still receives considerable doses in the final plan. In Intensity
Modulated Radiotherapy (IMRT) it is possible to overcome this problem by
achieving desired dose distribution with its ability to provide sharp dose
gradients at the junction of target volume and the adjacent critical organs.
In order to explore the advantages of IMRT treatment and extend it to the gastric cancer patients, a retrospective study was carried out by the first author (KMM) at his previous institution on 15 patients of gastric cancer treated with 3D-CRT.
In this article the authors
describe the planning methods used and show the comparison of results for
4F-CRT and IMRT plans of a representative patient. They also furnish DVH
comparison results of conventional 3F-CRT, 4F-CRT and dynamic IMRT for all 15
Materials and Methods
3D Radiation Treatment Planning System (RTPS) Eclipse
(version 6.5, Varian Ag, USA) with Helios inverse planning software was used
for treatment planning. High energy Linear Accelerator Clinac 2300 CD (Varian
Ag, USA) having 120 leaf millennium MLC was used for the delivery of
treatments. Fifteen patients planned and treated with three/four field 3DCRT
were taken up for a retrospective study by re-planning with dynamic IMRT
technique and comparing the dose distributions in PTV and organs at risk. For
all the cases radiation was given in 25 fractions of 1.8 Gy to a total dose of
45 Gy in 5 weeks. CT images of 5mm thickness at different transverse sections
away from the mid plane were taken to create a 3D image. Initially the 3D
forward planning of 3F-CRT with three fields (AP and two laterals) was done for
15 patients in conventional way. Then 4F-CRT planning with four fields (AP, two
laterals and PA) was done for each patient. In both cases, appropriate wedges
were used to obtain uniform dose distribution in the target volume. The beam
energies (6 and 15MV), beam weightings and MLC leaf positions were optimized by
forward planning to reduce the doses to the critical organs and achieve a
better homogeneous dose distribution in the PTV.�������������
Following the 3DCRT plans, dynamic IMRT plans were created
on the same CT images with structures. Seven fields of 6MV energy with equal
separation of gantry angles were used. A constraints template was created and
applied to all the 15 patient plans. Wherever required and achievable, the
constraints were changed to obtain possible minimum doses to critical organs
without compromising the PTV coverage of at least 95% dose to 95% of PTV
Comparison parameters: To asses the target coverage
and normal tissue sparing the following parameters were used.
- A uniformity index was used and defined as:
Where D5 and D95 are the minimum doses delivered to 5%
and 95%, respectively of the PTV as previously described by Wang et al. 
and Kesheng et al. . In addition, to assess target coverage, the mean and
maximum doses to PTV, percentage of target volume receiving at least 95% of the
prescribed dose TV95(%) and the dose to 1% of target volume D1(%)
were calculated. ��������������
- Radiation dose homogeneity index (HI), which was defined by Nutting et
al.  and Pezner et al.  as the difference in PTV dose between D1 and
D99 divided by the prescription dose was calculated. Smaller HI
corresponds to more homogeneous dose distribution in PTV.
- The conformity index, CI was calculated by using the following formula
where, TV95 is the volume of target covered by the 95% isodose line,
TV is the total target volume and V95 is the volume of tissue
covered by the 95% isodose line. The value of CI varies between 0 to 1 and a
value close to 1 gives better conformity of dose to the PTV.
- The sparing of the organs at risk was evaluated by comparing their
maximum and mean doses. D2/3 and D1/3, defined as the
dose received by 2/3 and 1/3 volumes of the organ respectively, were also
analysed for tolerance limits [19, 20].
- The percentage of volumes of organs at risk (OARs) receiving a dose more
than their corresponding tolerance limit (V>TL) were compared.
The values of the above parameters of 15 cases planned by
conventional forward planning with 3F-CRT, 4F-CRT and the dynamic IMRT
technique were compared with the help of their dose volume histograms.
Statistical analysis was performed with the two-tailed paired t-test. A p-value
of p<0.05 was considered statistically significant.
All three planning techniques produced acceptable dose
distributions to the planned target volume. All the dose coverage parameters of
PTV for the 3F-CRT and 4F-CRT plans showed similar and comparable values
without significant differences. The isodose distributions obtained on an axial
slice at the isocenter plane of a representative patient for 4F-CRT and IMRT
are shown in Figure 1. The plan comparison DVH curves for PTV and OARs of the
same patient for 4F-CRT and IMRT are shown in Figure 2. The analysed data of
fifteen patients with the mean doses to the PTV and comparison of dose coverage
with 3D-CRT and IMRT treatment plans is shown in Table 1. The results indicate
that there was a statistically significant and considerable difference in the
dose coverage of PTV with IMRT (p<0.001) compared to both 3D-CRT
plans. The average lower values of SD, UI, HI and higher values of CI for IMRT
plans compared to the 3F-CRT and 4F-CRT plans confirms the advantage of IMRT
plans over both 3D-CRT plans.
The dose coverage of OARs with 3F-CRT, 4F-CRT and IMRT
plans along with the p-values are shown in Table 2. The average mean dose
values of liver were less in 4F-CRT plans compared with that in 3F-CRT plans. There
was however, a significant (p<0.001) dose reduction in liver with
IMRT plans compared to both 3D-CRT plans.
The average mean values and other doses of both the
kidneys and the spine with the 3F-CRT plans were lower than that with the
4F-CRT plans. The reduction of liver dose in 4F-CRT and reduction of doses in
kidneys and spine with 3F-CRT plans were attributed to the addition of the PA
field in the 4F-CRT plans. The IMRT plans were able to achieve lower values of
doses in the right kidney compared to that of both 3D-CRT plans, whereas the
dose values in the left kidney were comparable. Similarly the dose values in
the spinal cord with IMRT plans were lower than that with the 4F-CRT plans and
slightly higher than that with the 3F-CRT plans.
In the case of bowel, all the mean dose values were
similar and comparable in both 3D-CRT plans and they were significantly reduced
in IMRT (p<0.001) plans. In all OARs the percentage of volumes
receiving more than their tolerance doses were reduced significantly (p<0.001)
with IMRT plans compared with both 3D-CRT plans.
The toxicity associated with adjuvant radiotherapy using
conventional 3DCRT techniques is significant. This is because of the standard
target prescribed dose of 45 Gy well exceeds the tolerance of surrounding
critical organs, namely kidneys and liver. Thus one has to compromise either in
prescription to treat at tolerance doses of normal tissues rather than to the
specific tumoricidal dose or in tailoring of the conventional treatment
volumes. In both cases, local control and survival may be compromised. As IMRT
delivers more conformal dose to the target by sparing surrounding critical
structures, it allows complete target coverage to full dose and improves
locoregional control and reduces toxicity. A number of studies have
demonstrated the superiority of the physical dose distribution of IMRT compared
to 3DCRT in the treatment of gastric cancers [21, 22].
The comparison of 3F-CRT and 4F-CRT plans showed that the
dose coverage of PTV in both cases was similar and comparable. But as expected
from the use of the additional PA field in 4F-CRT, the dose to liver was less
compared to the 3F-CRT plan, while the doses to the kidneys and spinal cord
were slightly more in 4F-CRT plans than in 3F-CRT plans. However, this marginal
dose differences in OARs would not give overall clinical significance between
the two techniques. Depending upon the shape and the size of the PTV and
critical organs, by comparing the DVH values, either one of the plans can be
In this study, the PTV from IMRT plans showed a systematic
and significant improvement in terms of target coverage and homogeneity
compared to 3D-CRT plans. Conformity index is used to evaluate the clinical
evidence of better treatments. The results showed that IMRT treatment plans
give considerable improvement of dose conformity to PTV with higher value of CI
compared to both 3F-CRT and 4F-CRT plans. Improved conformity may help to
deliver higher doses to the PTV without delivering more doses to the
surrounding normal tissue. This was clearly demonstrated by the isodose
distributions and DVH curves shown in Figures 1 and 2, respectively. The
uniformity index values calculated for the target volume also showed
significant advantage of IMRT plans over 3D-CRT plans.
With respect to all OARs, IMRT is able to keep the mean
dose below their tolerance levels in contrast with 3D-CRT. This dose reduction
in non-target structures without compromising the dose in the target volumes
could lead to additional clinical advantages, because side effects during or
following treatment might be reduced. On the other hand, dose reduction in the
OAR volumes could allow additional dose escalation to the target structures.
Therefore the capability of dose conformity of IMRT is clinically beneficial to
the patients of gastric cancer.
With IMRT treatments, the mean dose to the liver was
reduced by 9.6% and 5% when compared with the 3F-CRT and 4F-CRT plans
respectively. This reduction of dose may appear small, but the mean values of D2/3,
D1/3 and percentage of volume receiving more than the tolerance
limit were reduced considerably compared to both 3D-CRT plans, which helps in
reducing the toxicity.
In the case of kidneys and spinal cord, though there was a
smaller difference in the mean doses with the plans of three techniques, mean
values of D2/3,D1/3 and percentage of volumes receiving
more than their tolerance limit were reduced significantly with IMRT (p<0.0001)
plans. The tendency of reduction in doses to OARs with IMRT obtained in this
study was similar to that of earlier studies reported by Milano et al.  and
Kataria et al. .
The bowel contour consisting of small and large intestines
was done and no constraints were given in IMRT plans. Since it is a mobile
organ, the authors wanted to verify the dose distribution and compare the
values with these three techniques. The results showed that all the dose
parameters of bowel in three field and four field conformal plans were
comparable and IMRT plans reduced them considerably. The reduction of dose in
OARs with IMRT plans may be due to the use of more number of fields with
appropriate angle selection, which causes reduction of entrance and exit dose
to those organs.
IMRT plans improve the homogeneity and conformity of dose
distribution in the target volume. The uniformity index and standard deviation
(SD) values also confirmed a better 3D dose homogeneity in the PTV with the
IMRT technique. With this method, the maximum dose coverage around the PTV has
reduced considerably. In the treatment of gastric malignancies IMRT reduces the
mean dose and the dose above threshold to critical normal tissues, particularly
to the liver and kidneys. With this technique, the desired dose distribution
can be achieved due to its ability to provide sharp dose gradients at the
junction of target volume and the adjacent OARs. Overall, the doses to all the
OARs were lower for IMRT plans and were in acceptable limits. The advantages of
IMRT plans include both improved planning target volume coverage and improved
sparing of critical organs.
In conclusion, this study suggests a dosimetric benefit of
IMRT over conventional 3D-CRT planning and indicates the importance of IMRT in
the adjuvant treatment of gastric cancer. The study helped the authors to
understand the role of IMRT in detail and created confidence to consider the
same to treat the patients with carcinoma of gastric cancers. However, the
superiority of IMRT over conventional 3D-CRT must be mitigated with the caution
for organ motion. Currently the authors are studying the effect of organ motion
in the upper abdomen as a prerequisite for the use of IMRT for patient
treatment to further evaluate doses received by these moving organs.
The authors thank Director General, Royal Hospital for kind permission to publish the above work.
Figure 1 Isodose curves on an axial slice at isocenter plane of a representative patient for 4F-CRT and IMRT. The lower part of the figure shows the isodose distribution on the coronal and sagittal plane of the corresponding slice.
Figure 2 Comparison of DVH curves of 4F-CRT and IMRT plans of a representative patient for (a) PTV, Liver and Bowel, (b) Left kidney, Right Kidney and Spinal cord.
Table 1 Comparison of the average dose parameters of 15 patients for the PTV among the three planning techniques.
Table 2 Comparison of average dose distribution in the Organs at risk (OARs) for a prescribed dose of 45Gy for 15 patients.
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|Received 25 January 2010; received in revised form 20
February 2010, accepted 20 April 2010
Correspondence: Department of Radiotherapy, Krishna Institute of Medical Sciences, Hyderabad, India. E-mail: firstname.lastname@example.org (Kammari Krishna Murthy).
Please cite as: Murthy KK, Shukeili KA, Kumar SS, Davis CA, Chandran RR, Namrata S,
Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT, Biomed Imaging Interv J 2010; 6(3):e29