|Year : 2014 | Volume
| Issue : 4 | Page : 871-877
Dosimetric comparison between Volumetric Modulated Arc Therapy (VMAT) vs Intensity Modulated Radiation Therapy (IMRT) for radiotherapy of mid esophageal carcinoma
Tejinder Kataria, HB Govardhan, Deepak Gupta, U Mohanraj, Shyam Singh Bisht, R Sambasivaselli, S Goyal, A Abhishek, A Srivatsava, L Pushpan, V Kumar, S Vikraman
Department of Radiation Oncology, Medanta-The Medicity, Gurgoan, Haryana, India
|Date of Web Publication||9-Jan-2015|
H B Govardhan
Department of Radiation Oncology, Medanta-The Medicity, Sector 38, Gurgaon, Haryana - 122 001
Source of Support: None, Conflict of Interest: None
Aims: Dosimetric comparison of VMAT with IMRT in middle third esophageal cancer for planning target volume (PTV) and organs at risk (OAR).
Materials and Methods: Ten patients in various stages from I‒III were inducted in the neo-adjuvant chemoradiation protocol for this study. The prescribed dose was 4500 cGy in 25 fractions. Both VMAT and IMRT plan were generated in all cases and Dose Volume Histogram (DVH) comparative analysis was performed for PTV and OAR. Paired t-test was used for statistical analysis.
Results: The PTV Dmean and D95 in IMRT and VMAT plan were 4566.6 ± 50.6 cGy vs 4462.8 ± 81.8 cGy (P = 0.1) and 4379.8 ± 50.6 cGy Vs 4424.3 ± 109.8 cGy (P = 0.1), respectively. The CI and HI for PTV in IMRT vs VMAT plans were 0.96 ± 0.02 vs 0.97 ± 0.01 (P = 0.4) and 10.58 ± 3.07 vs 9.45 ± 2.42 (P = 0.2), respectively. Lung doses for VMAT vs IMRT were 4.19 vs 2.59% (P = 0.03) for V35-7.63 vs 4.76% (P = 0.01) for V30-13.6 vs 9.98% (P = 0.01) for V25-24.77 vs 18.57% (P = 0.04) for V20-46.5 vs 34.73% (P = 0.002) for V15. The Mean Lung Dose (MLD) was reduced by VMAT technique compared to IMRT; 1524.6 ± 308.37 cGy and 1353 ± 186.32 cGy (P = 0.012). There was no change in Dmax to spinal cord in both the techniques. There was a dose reduction by VMAT compared to IMRT to the heart but it was statistically insignificant; V35-6.75% vs 5.55% (P = 0.223); V30-12.3% vs 10.91% (P = 0.352); V25-21.81% vs 20.16% (P = 0.459); V20-38.11% vs 32.88% (P = 0.070); V15-61.05% vs 54.2% (P = 0.10).
Conclusion: VMAT can be a better option in treating mid esophageal carcinoma as compared to IMRT. The VMAT plans resulted in equivalent or superior dose distribution with a reduction in the dose to lung and heart.
目的：比较VMAT 和 IMRT在中段1/3食管癌计划靶区体积（PTV）和危及器官（OAR）的剂量。
结果：在IMRT和VMAT计划中，PTV 平均剂量和D95分别为4566.6 cGy±50.6 vs 4462.8±81.8 cGy（P = 0.1）和4379.8±50.6 cGy vs 4424.3±109.8 cGy（P = 0.1）。IMRT 相比 VMAT计划PTV的CI和HI分别为 0.96±0.02 vs 0.97±0.01（P = 0.4）和10.58±3.07 vs 9.45±2.42（P = 0.2）。肺剂量VMAT与IMRT分别为:V35 4.19和2.59%（P = 0.03），V30 7.63 vs 4.76%（P = 0.01），V25 13.6 vs 9.98%（P = 0.01），V20 24.77 vs 18.57%（P = 0.04），V15 46.5 vs 34.73%（P = 0.002）。平均肺剂量（MLD）较比，VMAT较IMRT减少，分别为1524.6±308.37 cGy和1353±186.32 cGy（P = 0.012）。脊髓最大剂量在两种技术中没有改变。心脏剂量VMAT相比IMRT有减少，但无统计学意义；V35 6.75% vs 5.55%（P = 0.223）；V30 12.3% vs 10.91%（P = 0.352）；V25 21.81% vs 20.16%（P = 0.459）；V20 38.11% vs 32.88%（P = 0.070）；V15 61.05% vs 54.2%（P = 0.10）。
Keywords: Intensity modulate dradiation therapy , mid esophageal carcinoma, volumetric modulated Arc therapy
|How to cite this article:|
Kataria T, Govardhan H B, Gupta D, Mohanraj U, Bisht SS, Sambasivaselli R, Goyal S, Abhishek A, Srivatsava A, Pushpan L, Kumar V, Vikraman S. Dosimetric comparison between Volumetric Modulated Arc Therapy (VMAT) vs Intensity Modulated Radiation Therapy (IMRT) for radiotherapy of mid esophageal carcinoma. J Can Res Ther 2014;10:871-7
|How to cite this URL:|
Kataria T, Govardhan H B, Gupta D, Mohanraj U, Bisht SS, Sambasivaselli R, Goyal S, Abhishek A, Srivatsava A, Pushpan L, Kumar V, Vikraman S. Dosimetric comparison between Volumetric Modulated Arc Therapy (VMAT) vs Intensity Modulated Radiation Therapy (IMRT) for radiotherapy of mid esophageal carcinoma. J Can Res Ther [serial online] 2014 [cited 2020 Mar 28];10:871-7. Available from: http://www.cancerjournal.net/text.asp?2014/10/4/871/138217
| > Introduction|| |
Esophageal cancer is the 8 th most common cancer worldwide. In 2012, an estimated 455,784 new esophageal cancer cases were diagnosed and approximately 400,156 deaths occurred worldwide. In India it is the 4 th common among cancer and the 3 rd common cancer related mortality.  The projected incidence of esophageal cancer in India by 2020 is estimated to be 42,513. 
Radiotherapy is a major treatment method for esophageal carcinoma as more than 60% of the patients are diagnosed at an advanced stage which cannot be resected. Traditionally, cancers of the esophagus have been treated using an anteroposterior/posteroanterior (AP/PA) field arrangement up to cord tolerance dose, followed by an off-cord boost.  Other beam arrangements have included the 4-field box technique, with less weight on the lateral beams in an effort to reduce lung dose, and a 3-field technique with an AP field and 2 posterior oblique fields. Treatment planning and delivery for esophageal cancer has progressed rapidly over the past 5 years. 3D conformal radiation therapy (3D-CRT) was the planning method of choice for many years.  Innovative technologies in radiation delivery such as intensity-modulated radiotherapy (IMRT) offer the potential for improved tumor coverage, while reducing the doses delivered to the surrounding normal tissues. Clinical studies have yielded good dosimetry and patient outcome by IMRT. ,,,, To reduce the radiation dose to critical normal structure integration of different planning modality is required.The volumetric modulated arc therapy (VMAT), a novel form of IMRT, first proposed by Yu in 1995  allowed for intensity-modulated radiation delivery during gantry rotation with dynamic multi-leaf collimator (MLC) motion, variable dose rates and gantry speed modulation. VMAT, through the dynamic modulation of angular dose rate and multileaf collimator motion, can achieve a highly conformal dose distribution while decreasing treatment time. Due to its shorter treatment times, the likelihood of patient movement during treatment, which can potentially lead to PTV miss is reduced. Secondly, VMAT can be beneficial for the treating facility because, when compared with IMRT, this technique is more efficient for use of both monitor units and the therapists time. With regards to the amount of time required to plan VMAT vs IMRT cases, the planning times as evaluated by staff dosimetrists, were comparable for VMAT and IMRT cases.  VMAT had already been investigated for prostate cancer, small brain tumors and cervix uteri cancer. ,, These studies have generally shown that VMAT is able to produce similar or better dose distributions, while achieving a reduction in treatment time and a reduction in monitor units (MU).
We performed a planning study to compare VMAT with conventional IMRT in the middle third esophageal cancer in dosimetry to planning target volume (PTV) and organs at risk (OAR) and their efficiency.
| > Materials AND METHODS|| |
Ten male patients with middle third esophageal cancer previously treated with IMRT in our department, were selected for this study, Six patients were in stage III, 3 patients were in stage II and one patient was in stage I, according to the American Joint Committee (AJCC) on Cancer 2010 Guidelines. Details are shown in [Table 1].
Patients were aged between 52-80 years with an average age of 66.5 years. Most of the patients presented with dysphagia and/or weight loss. In most of the patients, histology was moderately differentiated squamous cell carcinoma (6/10) followed by well-differentiated squamous cell carcinoma [Table 1]. Positron emission tomography/computed tomography was used to rule out the existence of distant metastases, and 8 patients received weekly concurrent chemotherapy. A thoracic mould is made by using uniform thermoplastic cast in supine position with hand kept above head. Patients were simulated with a computed tomography simulator using 1-3mm slice thickness taken from C2 to L4 vertibra. For allthe patient's tumor, board opinion and consent for radiation therapy is taken from the patient before this procedure. The patients were planned for neo-adjuvant concurrent chemoradiation as per the institutional protocol.
The gross tumor volume (GTV), clinical target volume (CTV), planning target volume (PTV) and lymph nodes as well as the organs at risk (OAR) including lung, heart and spinal cord were contoured on Focal Sim contouring platform by the treating physician as per RTOG 0436 protocol.  The GTV was contoured on the basis of visible tumor or lymph nodes on CT scan with the help of fusion with PET CT and MRI. The GTV was confirmed by radiologist as per our departmental protocol. The CTV was delineated with 3-4.5 cm superior-inferior margins and 1.5 cm radial margin with respect to the GTV. For the lymph nodes, 1 cm uniform margins were given in all directions. The anotomical boundaries like lung and bones are considered while contouring CTV. The planning target volume (PTV) was delineated with additional 0.5 cm margin to the CTV depending on GTV delineation accuracy and nearby critical structures. The prescription dose was 45 Gy in 25 fractions of 1.8 Gy per fraction. Organs at risk (OARs) included the heart, lungs, healthy esophagus, spinal cord, and trachea. The organs at risk (OAR) constraints given for lung, heart and spinal cord for planning and optimization are given in the [Table 2]. Contoured kVCT images and structure set were then exported from Focal system to Monaco planning work station.
VMAT plans were generated with Monaco treatment planning system (Version 2.03.01, Elekta Systems) in which continuous gantry motion is modelled as a number of discrete angle segments and MLC apertures are progressively added throughout optimization. MU per gantry angle was optimized using a variable dose rate. Gantry incremental angle was kept at 10 degree. Monte Carlo dose calculation algorithm was used with heterogeneity correction and a grid size of 3.5mm. All patients treated with single arcs were planned with start and stop angles of 180 to 180 degree (a complete arc of 360 degree), delivered with clockwise rotation. To ensure that 100% of the PTV received at least 95% of the prescribed dose and 0% to receive not more than 107%. A minimum dose of 95% of the prescribed dose was the benchmark used for evaluating coverage of the PTV. Minimum segment size allowed was 2 cm 2 and segment weight optimization factor was kept at 3 i.e. segments having MUs lesser or equal to three were combined to single segment so the minimum MUs per segment allowed were 4.
The IMRT plan was optimized to cover at least 95% of PTV by 95% of the prescribed dose while minimizing the dose to OARs as much as possible. Inverse planning optimization was performed using Monaco TPS v 2.03.01. Dose calculation was done with Monte Carlo semi-biological algorithm with 3.5 mm grid resolution. Tissue inhomogeneities were considered in the treatment planning optimization process. An optimization with 100 iterations was then applied and followed by a semiautomatic segmentation (minimum 3 cm step size). Segments with less than ≤2 MUs were expelled from the plan. A seven non coplanar field beam arrangement was used for all IMRT plans. Beam geometry consisted of each treatment field with the following gantry angles: 0°, 51°, 102°, 153°, 204°, 255° and 306°. Isocenter was kept at the same point from VMAT for all IMRT plans. As with VMAT, the normal tissue objective feature in optimization was used for all IMRT plans.
All plans were evaluated via the standard DVH. For the PTV, D99% and D1% were chosen as minimal and maximal doses, respectively. Other parameters analyzed were D95%, D5%, D Mean, Homogeneity Index (HI), Conformity Index (CI) and Uniformity Index (UI). Homogeneity index (HI) was evaluated as the difference between the maximum and minimum dose to the target volume (D1% and D99%, respectively) divided by the prescription dose and multiplied by 100. , Uniformity index (UI) , was also used and defined as the ratio of D5% to D95%. Both HI and UI were used following the methodology for assessing overall plan homogeneity established in the planning study for anal cancers by Joseph et al.
The conformity of dose distribution was assessed by means of conformity index (CI) which was defined as the ratio between the volume receiving at least 95% of 4500 cGy and the volume of the PTV. Higher values of CI represented a better PTV conformity. 
The OAR dosimetry was analyzed for each patient, for the lung and heart, mean dose, and volumes of lung receiving dose at least 5, 10, 15, 20, 25, 30, 35 and 40 Gy (V5, V10, V15, V20, V25, V30 and V40). For the spinal cord maximum dose was analyzed. To determine statistical significance, two-tailed paired t-tests were performed with P values < 0.05 considered to be significant. All computations were performed using the Statistical Package for the Social Sciences software (SPSS) program (Version 16.0).
| > Results|| |
The GTVs ranged from 10.40-100.25 cc and the average volume was 45.41 cc [Table 1]. PTVs ranged from 294.6-993.5 cc, with an average of 517.2 cc. Regarding coverage of the PTV, both techniques were adequate in providing 95% of the prescription dose to 100% of the PTV volume. With a prescription dose of 4500 cGy to the PTV, the dosimetric results Dmean, D95, HI, CI and UI for all ten patients in both techniques are tabulated in [Table 3]. The mean ± standard deviation of the Dmean and D95 for the PTV in the IMRT and VMAT plan were: Dmean-4566.6 ± 50.6 cGy vs 4462.8 ± 81.84 cGy (P = 0.101) and D95-4379.8 ± 50.60 cGy vs 4424.3 ± 109.82 cGy (P = 0.140) respectively. On an average, the mean doses and D95 were 2.33% and 1% greater for the VMAT plans respectively but the difference is not statistically significant [Table 4].
|Table 4: Presents average dose-volume statistics for the PTV as well as average OAR DVH parameters|
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The conformity Index for PTV in the IMRT and the VMAT plans was 0.96 ± 0.02 and 0.97 ± 0.01 (P = 0.480), respectively. The Homogeneity Index for PTV in the IMRT and the VMAT plans was 10.58 ± 3.07 and 9.45 ± 2.42 (P = 0.297), respectively. The Utility Index (UI) for the PTV was 1.079 ± 0.02 and 1.074 ± 0.02 (P = 0.310) in the IMRT and VMAT respectively. We can observe from the results there was no difference between VMAT and IMRT in dose distribution.
Dose distributions for one patient (patient no 4) with corresponding cumulative DVHs for both PTV and OAR with both the plan is shown in [Figure 1],[Figure 2],[Figure 3] and [Figure 4]. The absolute plan parameters for lungs, heart and spinal cord are summarized in [Table 4]. DVH of OAR in one patient is shown in [Figure 1]. The VMAT technique provided the statistically significant (P < 0.05) improvement in lung sparing, particularly for the V35, V30, V25, V20, V15 and Mean Lung Dose (MLD), as shown on a case-by-case basis in [Table 4]. The V35, V30, V25, V20, V20 of the lungs was significantly reduced by the IMRT plans compared to VMAT plans; V35-4.19% vs 2.59% (P = 0.032); V30-7.63% vs 4.76% (P = 0.015); V25-13.63% vs 9.98% (P = 0.019); V20-24.77% vs 18.57% (P = 0.04); V15-46.5% vs 34.73% (P = 0.002); V10-68.98% vs 61.27% (P = 0.009). The MLD was reduced significantly by VMAT technique compared to IMRT; 1524.6 ± 308.37 cGy and 1353 ± 186.32 cGy (P = 0.012). For the V45, V40, V10 and V5 there is a reduction in the lung volume but they are not statistically significant (P > 0.05).
|Figure 1: Figure showing dose distribution by VMAT and IMRT in sagital section|
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|Figure 2: Figure showing dose distribution by VMAT and IMRT in transverse section|
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|Figure 3: Figure showing dose distribution by VMAT and IMRT in coronal section|
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For the heart there was no significant dose difference between the two plans but a slightly better plan was achieved on VMAT compared to IMRT in V35-6.75% vs 5.55 (P = 0.223); V30-12.3% vs 10.91% (P = 0.352); V25-21.81% vs 20.16% (P = 0.459); V20-38.11% vs 32.88% (P = 0.070); V15-61.05% vs 54.2% (P = 0.10). For V10 and V5 IMRT achieved a better plan compared to VMAT; V10-71.62 ± 26.88 vs 71.95 ± 26.48 (P = 0.970) and V5-85.79 ± 21.66 vs 86.52 ± 21.00 (P = 0.795) but they are statistically insignificant. The mean heart dose was reduced by VMAT technique compared to IMRT; 1740.3 ± 610.02 cGy and 1666.2 ± 591.14 cGy (P = 0.163). There is no change in D max to spinal cord by both the techniques. Dmax-3606.8 ± 326.54 cGy by IMRT and 3663.5 ± 336.36 cGy for VMAT and statistically insignificant (P = 0.976). The duration of treatment time between IMRT and VMAT was found to be 14.6 ± 1.8 and 7.4 ± 1.6 minutes (P = 0.002).
| > Discussion|| |
Studies by both Yang et al., and Hazard et al., concluded that new and innovative treatment strategies are needed to improve outcomes for patients with esophageal cancers. These observations lead to the evaluation of the IMRT and Arc strategy previously employed successfully in simultaneous infield boost for brain metastases.  While the current standard treatment is pre-operative concurrent chemoradiation, previous studies of various novel radiation therapy techniques for treatment of carcinoma of the esophagus have provided mixed results. , All patients in this study were diagnosed with mid-esophageal carcinoma, the PTV volumes and locoregional extent varied from patient to patient.
Study by Spencer et al.,  suggests that VMAT is essentially equivalent to IMRT for treatment of the esophagus from a dosimetric perspective. They showed that a similar isodose distribution can be compared. On an average, the greatest difference in organ sparing was 2.12 Gy and with an average difference of 50 cGy. For coverage of the PTV, IMRT provided a slightly more homogenous dose distribution and VMAT had a tendency to produce many cold spots inside the GTV. But in our study, the VMAT was equivalent and compared to IMRT in both coverage and the dosimetry as showed in [Table 3] and [Table 4]. We did not get any cold spots in all IMRT and VMAT plans. The organ sparing is definitely significant in lung by 170 cGy in MLD and 75 cGy for mean heart dose.
In the study by L V Benthuysen et al.,  regarding coverage of the PTV, both IMRT and VMAT were adequate in providing 95% of the prescription dose to 100% of the PTV volume, with the exception of 1 VMAT case in which the minimum dose to the PTV was 90%. On average, the mean doses and maximum doses were 1.5% and 3.2% greater for the VMAT plans, respectively. In our study, both the VMAT and IMRT had 100% coverage to 95% of the prescribed dose in all cases, mean dose is 2% more for IMRT and maximum and minimum dose is around 1% more for VMAT than IMRT. In a study by Li yin showed, CI and HI for the mid esophagus is in the range of 0.67 ± 0.08 vs 0.76 ± 0.05 and 1.11 ± 0.02 vs 1.12 ± 0.02 for 7 field IMRT and one arc VMAT, respectively.  In our study, CI and HI for IMRT and VMAT were found to be 0.96 ± 0.02 vs 0.97 ± 0.01 and 10.58 ± 3.07 vs 9.45 ± 2.42 showing VMAT is better plan compared to IMRT but statistically insignificant (P > 0.05). In a study by Spencer et al., it showed the UI and HI to be 1.11 ± 0.03 (P < 0.001) and 0.17 ± 0.04 (P = 0.009), respectively for single arc VMAT which is inferior to 2 arc VMAT. In our study, UI for IMRT and VMAT were shown to be 1.07 ± 0.02 in both techniques, showing that both techniques achieved uniform dose distribution.
Wei et al., stated that pericardial effusion was seen in 13% patients when V30 to the heart was kept below 46%. In our study, the average V30 for the heart was below 13% for both modalities, and VMAT delivered better dose reduction to heart as compared to IMRT; V30-12.3% vs 10.91% (P = 0.352). Study by Li Yin et al., showed dose to the lungs, VMAT provided better sparing in terms of V20 and V30. For the heart, VMAT showed a lower percentage of V30, V40 or V50. In our study, dose to lung by VMAT was lower as compared to IMRT, V45, V40, V35, V30, V25, V20, V15, V10, V5 is reduced by 0.15%, 0.6%, 1.6%, 2.9%, 3.65%, 6.2%, 7.8%, 7.7% and 2.4% respectively. For the heart slight dose reduction by VMAT as compared to IMRT V45, V40, V35, V30, V25, V20, V15, and V5 is reduced by 0.13%, 0.85%, 1.2%, 1.4%, 1.7%, 5.3%, 6.8% and 27%. For V10 IMRT delivered low dose compared to VMAT-85.79 vs For conventional fractionated regimens (2 Gy/fraction), V20 and MLD were the traditional parameters used to predict for lung toxicity, however, emerging data suggests that percentage of lung volume receiving lower doses may be predictive of pulmonary toxicity. VMAT plans offer the potential to significantly escalate the coverage of the low-dose area (V5 and V10) because all doses are deposited within the plane of the arc, instead of being spread out in non-coplanar directions.  Mean V5 in VMAT is beyond 80% and it might increase the potential pulmonary toxicity. In our study, V5 was found to be <85% in both the techniques. Wei et al.,  found that dose to heart V30 >46% and <46% was associated with rates of pericardial effusion of 73% and 13%, respectively. In our study, V30 achieved was <15 Gy in both the techniques and VMAT achieved a better plan than IMRT. Hawkins et al., evaluated the capability of VMAT to reduce heart and cord dose while maintaining lung V20 <20% in lower gastroesophageal tumors. IMRT (4Field) and VMAT plans showed that VMAT provided a significant reduction in heart V30 (31% vs 55%) with a better CI in a shorter time. In a study by L V Benthuysen et al., a large difference in organ sparing was determined to be the maximum dose delivered to the spinal cord of 2.12 Gy greater with VMAT is considered clinically insignificant.  In our study, no difference was observed between the two plan techniques in Dmax to spinal cord. 85.82 (P > 0.05).
Lee et al., showed retrospectively that to reduce postoperative pulmonary complications in patients with esophageal cancer undergoing preoperative concurrent chemoradiation, V15 below 30% and the V20 should kept below 20%.  In our study, V20 to lung was achieved 25% by IMRT and 18% by VMAT and V15 to lung were found to be 46% and 34% respectively.
The National Comprehensive Cancer Network Guidelines recommend dose limits for selecting critical normal structures, i.e., the spinal cord doses should not exceed 45 Gy, and one-third of the heart should receive less than 50 Gy. The dosimetric parameters of lung injury risk were mainly studied on lung cancer irradiation, and increased risk of radiation pneumonitis correlated with heterogeneous parameters, such as MLD, the percentage of lung volume receiving at least 20 Gy (V20),13 Gy (V13),10 Gy (V10) or 5 Gy (V5), in which V20 was a recognized indicator confirmed by several studies. Based on pooled data from 540 patients irradiated for thoracic malignancy, the calculated risk of grade ≥2 pneumonitis was 43%, 18% and 11% for the MLD of 24-36, 16-24 and 8-16 Gy, respectively. In our study, MLD was controlled below 16 Gy in both the techniques and are statistically significant, VMAT was delivered low dose compared to IMRT 15 Gy vs 13 Gy.
| > Conclusion|| |
In our study, we found that utilization of VMAT can offer a better option in treating mid esophageal carcinoma as compared to IMRT. The VMAT plans resulted in equivalent or superior dose distribution with a reduction in the dose to lung and heart. These results provide evidence in support of efficacy, safety, and improved efficiency for the clinical utilization of VMAT.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]