|Ahead of print publication
Evaluation of the organs at risk doses for lung tumors in gated and conventional radiotherapy
Sara Shahzadeh1, Somayeh Gholami2, Seyed Mahmood Reza Aghamiri1, Hojjat Mahani3, Mansoure Nabavi2
1 Department of Medical Radiation Engineering, Shahid Beheshti University, Tehran, Iran
2 Radiotherapy Oncology Research Centre, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Research Center for Molecular and Cellular Imaging, Tehran University of Medical Science, Tehran, Iran
Radiotherapy Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Keshavarz Blvd, Tehran 141556447
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of this study was to evaluate the organs at risk (OARs) doses for lung tumors in gated radiotherapy (RT) compared to conventional RT using the four-dimensional extended cardiac-torso (4D-XCAT) digital phantom in a simulation study.
Materials and Methods: 4D-XCAT digital phantom was used to create 32 digital phantom datasets of different tumor diameters of 3 and 4 cm, and motion ranges (MRs) of 2, 2.5, 3, and 3.5 cm and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe, and left upper lobe). XCAT raw binary images were converted to the digital imaging and communication in medicine format using an in-house MATLAB-based program and were imported to treatment planning system (TPS). For each dataset, gated and conventional treatment plans were prepared using Planning Computerized RadioTherapy-three dimensional (PCRT-3D) TPS with superposition computational algorithm. Dose differences between gated and conventional plans were evaluated and compared (as a function of 3D motion and tumor volume and its location) with respect to the dose-volume histograms of different organs-at-risk.
Results: There are statistically significant differences in dosimetric parameters among gated and conventional RT, especially for the tumors near the diaphragm (P < 0.05). The maximum reduction in the mean dose of the lung, heart, and liver were 6.11 Gy, 1.51 Gy, and 10.49 Gy, respectively, using gated RT.
Conclusions: Dosimetric comparison between gated and conventional RT showed that gated RT provides relevant dosimetric improvements to lung normal tissue and the other OARs, especially for the tumors near the diaphragm. In addition, dosimetric differences between gated and conventional RT did generally increase with increasing tumor motion and decreasing tumor volume.
Keywords: Four-dimensional-extended cardiac-torso phantom, gated RT, organs at risk doses
|How to cite this URL:|
Shahzadeh S, Gholami S, Aghamiri SM, Mahani H, Nabavi M. Evaluation of the organs at risk doses for lung tumors in gated and conventional radiotherapy. J Can Res Ther [Epub ahead of print] [cited 2019 Nov 22]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=268951
| > Introduction|| |
Breathing-induced organ motion has been identified as a significant source of uncertainty in the treatment planning of lung tumors.,,, Uncertainties in treatment planning and delivery may result in large discrepancies between the prescribed/reported dose and the dose, which was actually delivered to the lung tumor. Gated treatment delivery, irradiation in breath hold, real-time tumor tracking, or addition of safety margins in free-breathing are methods for compensation of this uncertainty.,,,, Respiratory gating minimizes internal target volume (ITV) margins by restricting the delivery to predetermined phases of respiration, during which tumor mobility is relatively limited.
The effect of organs at risk (OAR) delineations on the dosimetric parameters can be significant and will influence the treatment decision. The present study aimed to (1) evaluate the 4D-doses of OARs in gated radiotherapy (RT) compared to conventional RT and (2) evaluate the effects of tumor size, its location, and the motion ranges (MRs) on dosimetric of OARs in both gated and conventional plans. Our study was based on the extended cardiac-torso (XCAT) anthropomorphic model., XCAT includes a three-dimensional (3D) description of human anatomy based on the Visible Human Dataset and a 4D modeling of both cardiac and respiratory motion. In this study, digital phantom is a suitable tool because the tumor diameter (TD), MR, and tumor locations (TLs) can be changed arbitrarily. If we use patient data for this study, TD, MR, and TL cannot be changed arbitrarily. Therefore, we used digital phantom for this study. In the previous study, the digital phantom results were validated and compared with the clinical results.
To the best of our knowledge, this is the first work in which the 4D-doses of OARs are evaluated in gated and conventional RT using the XCAT digital phantom with different TDs, TLs, and MRs.
| > Materials and Methods|| |
32 digital phantom datasets of different TDs of 3 and 4 cm, and MRs of 2, 2.5, 3, and 3.5 cm were created using four-dimensional-XCAT (4D-XCAT) phantom. The voxel dimension was 1 mm (approximate) × 1 mm (approximate) × 3.1 mm. In this phantom, these tumors were set in the left lower lobe, left upper lobe, right lower lobe, and right upper lobe. The 4D computed tomography (4D-CT) dataset consisted of five discrete respiratory phases (0%–90% phase).
4D-CT images generated from 4D-XCAT phantom were imported into the PCRT-3D treatment planning system (TPS). The CT series reconstructed at end-exhalation was defined as the reference image data set because the time-averaged tumor position was found to be close to exhale as the tumor spent more time in exhale than in inhale., The gross tumor volume (GTV) was created on the reference CT peak-exhale images (50% phase). For XCAT digital phantom the tumor has known boundaries and volume. Therefore, the clinical target volume (CTV) was defined as being identical to the GTV (i.e., no GTV to CTV margin was applied). In conventional RT, an ITV was generated as the sum of all tumor positions in the 4D-CT images. To compensate for setup uncertainties, the planning target volume (PTV) in conventional TPS, PTVconventional, was generated by isotropically expanding the ITV by 5 mm. PTV for gated TPS, PTVgated, was determined by 5 mm isotropic expansion of the CTV, where 2 mm defines a narrow gating window consistent with free-breathing gating and 3 mm accounts for setup uncertainties. Depending on TD and TL, treatment planning was performed for X-ray photon beams of 6 or 18 MV energies that are available in our Varian Clinac 2100 linear accelerator, (Varian Medical Systems, Palo Alto, California, USA). The dose was calculated with a grid size of 3 mm and the superposition algorithm. Two plans were generated for each phantom.
The prescription dose was set to 200 cGy/fraction for a total of 30 fractions. All plans were normalized to 60 Gy prescribed to the PTV receiving 95% of the prescription dose, for both gated and conventional treatment plans.
The other OARs, including the heart, liver, and spinal cord were contoured on each image data sets following anatomic definitions.
The 3D conventional plan from the reference image data set was copied into each of the image data sets; one plan was created for each CT series/respiratory phase. All planning parameters (beam arrangement and isocenter position) remained unchanged.
Dose constraints to OARs were modified from the radiation therapy oncology group 0915 protocol. In this protocol, the lungs must have V20 (the lung volume receiving μ20 Gy) ≤30%, the mean lung dose is 7 Gy, the mean liver dose is 32 Gy, the heart must have V30 (the heart volume receiving μ30 Gy) <46% and V25 (the heart volume receiving μ25 Gy) <10% and the mean heart dose is 26 Gy, and the maximum spinal cord dose is 45 Gy.
Dose constraints to OARs of the reference conventional plan (3D plan), all conventional plans for the five respiratory phases, and the accumulated conventional plan (4D plan) were averaged and compared with 3D-gated plans.
For each methodology, mean dose and irradiated volume of OARs were obtained and analyzed for different TDs, TLs, and MRs.
For statistical analysis, a two-tailed paired t-test was used to evaluate the significance of the results from using the two planning methodologies by OriginLab software (OriginLab Corporation, Northampton, Massachusetts, Version 8.0724). Differences were considered statistically significant at value of P ≤ 0.05.
| > Results|| |
[Figure 1] shows the dose-volume histograms data for a case (with TD = 4 cm, TL = right lower lobe of the lung, MR = 30 mm). Results for all cases show that the gated plan provided a superior reduced dose to the lung, heart, and spinal cord, and improved sparing of the liver.
|Figure 1: Dose-volume histogram of organs at risks for conventional (solid) and gated (dashed) data for a case (with tumor diameter = 4 cm, tumor location = right lower lobe of the lung, motion range = 30 mm)|
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The mean absorbed dose to the lung, heart, and liver, and maximum dose to the spinal cord were decreased for all cases using gated plans. The mean and standard deviation of mean doses of OARs among two methods (gated and conventional) are shown in [Figure 2]. Statistically significant differences were observed between the two treatment plans (P < 0.05). The mean (Gy) ± standard deviation of maximum dose for spinal cord were 16.70 Gy ± 11.51 and 19.39 Gy ± 11.15 (P < 0.05) for the gated and conventional plans, respectively.
|Figure 2: Mean and standard deviation of mean doses of organs at risks among two methods (gated and conventional)|
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Dose reduction of the organs at risks as a function of tumor motion, size, and its location
[Figure 3] and [Figure 4] show the changes in mean doses and irradiated volumes of OARs as a function of MRs and TDs between two treatment plans for tumors were located in the right lower lobe of the lung. These figures showed that mean doses and irradiated volumes of OARs increased with increasing MR just for conventional treatment plans. Furthermore, these values increased with increasing TD from 3 cm to 4 cm for both treatment plans. Furthermore, mean doses and irradiated volumes of OARs were significantly lower for gated RT (with P < 0.05) (e.g., for MR = 25 cm and TD = 4 cm: Mean dose = 20.11 Gy and V20 = 41.82% for the lung, mean dose = 6.23 Gy, V25 = 10.67% and V30 = 8.1% for the heart and liver mean dose = 2.56 Gy for gated plan vs. mean dose = 23.13 Gy and V25 = 48.38% for the lung, mean dose = 7.15 Gy, V25 = 12.44% and V30 = 10% for the heart and liver mean = 11.06 for conventional plan). All cases with various MRs and TDs have similar results.
|Figure 3: Comparison of mean dose of (a) lung, (b) heart and (c) liver changes with the motion ranges for tumor diameters of 3 and 4 cm, located at right lower lobe of the lung, for both gated and conventional treatment plans|
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|Figure 4: Comparison of irradiated volume of the lung (a) and heart (b and c) changes with the motion ranges for tumor diameters of 3 and 4 cm, located at right lower lobe of the lung, for both gated and conventional treatment plans|
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The relevance between the TLs and mean doses, irradiated volumes of OARs for both gated and conventional treatment plans, for an MR of 30 mm are represented in [Table 1] and [Table 2], respectively. For the cases with tumors in the upper lobe, dosimetric values of the heart were near to zero for both treatment plans. In addition for the tumors in the right lower lobe, reduction in mean dose of the liver was significant, and for other cases, mean dose of the liver was near to zero, for both treatment plans. The results indicate that all dosimetric values were significantly lower for gated RT, particularly when the tumors located in the lower lobe of the lung (with P < 0.05).
|Table 1: Summary of mean doses of the lung (a) and heart (b) for gated and conventional plans for various tumor locations and diameters (motion range is 30 mm)|
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|Table 2: Summary of irradiated volume of the lung (a) and heart (b, c) for gated and conventional plans for various tumor locations and diameters (motion range is 30 mm)|
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| > Discussion|| |
In the present study, we evaluated the 4D-doses of OARs for lung tumors in gated and conventional RT using the XCAT digital phantom with different TDs, TLs, and MRs.
For the upper lobes tumors, dosimetric values for all OARs were negligible in both gated and conventional TPS. Thus, respiratory gated RT might be avoided for the upper lobe tumors due to longer treatment time compared to conventional techniques.
In the present work, for all 32 cases, the highest mean dose and irradiated volume values of the lung and heart were seen in lower lobe tumors for both treatment plans. Furthermore, for upper lobe tumors due to a smaller range of motion, smaller CTV to PTV margin is needed; therefore, a smaller lung and heart volumes received a high dose. Consequently, dosimetric differences between gated and conventional plans were larger for lower lobe tumors than for upper lobe tumors. Smaller respiratory-induced lung tumor motion for upper lobe tumors than middle and lower lobe tumors is reported in clinical studies., However, for lower lobe tumors, near the diaphragm, respiratory-gated RT could reduce the irradiated volume of the heart and lung normal tissue. The largest reduction of mean dose, V25, and V30 of the heart with gated RT were 1.31 Gy, 2.77%, and 2.47%, respectively. The largest reductions in mean dose and V20 of the lung for using gated RT were up to 5.32 Gy and 12.07%, respectively. Furthermore, significant reductions of the liver mean dose with respiratory gated can be achieved for the right lower lobe tumors. For these cases, the gated RT reduced the live mean dose by up to 10.05 Gy. These results are comparable to those already reported in clinical studies.,,, Giraud et al. have reported the mean dose and V20 of the lung 12.8 ± 5.1 Gy and 22.8% ±9.6% in gated RT and 15.6 ± 7.7 Gy and 26.5% ±12.5% in conventional RT, respectively. They also have reported the mean dose of the heart 10.9 ± 9.2 Gy and 13.1 ± 10.3 Gy in gated and conventional RT, respectively. Underberg et al. have reported the mean dose and V20 of the lung were reduced by 4.9% and 7% for gated RT versus conventional RT.
For tumors with the motion of 20 mm and more, investigated values for MR, significant dose reduction was observed by the gated method. With increasing in MR from 20 mm to 35 mm, the largest reduction in mean dose of the lung, heart, and liver with gated RT were 6.11 Gy, 1.51 Gy, and 10.49 Gy, respectively.
| > Conclusions|| |
The use of the gated RT technique for lung tumors leads to relevant dosimetric benefits to the organ at risks, especially when there are tumors near the diaphragm. In this study, we quantified the benefits of gated RT versus conventional RT in sparing normal tissues, using XCAT digital phantom. The present study also showed that how tumor size, its location, and MR can affect the dose distributions and dosimetric OARs parameter for conventional and gated RT. Using a 4D digital phantom gives us the flexibility to generate desired models to conduct a comprehensive study of the effect of the tumor size, its location, and motion range on dosimetric parameters.
Financial support and sponsorship
This research has been supported by Tehran University of Medical Sciences and Health Services with grant number 96-02-207-35325.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]