|Ahead of print publication
Dosimetric analysis of three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric modulated arc therapy in prostate cancer radiotherapy
Fenny Gozal, Soehartati Argadikoesoema Gondhowiardjo, Henry Kodrat, Wahyu Edy Wibowo
Radiation Oncology Department, Rumah Sakit Cipto Mangunkusumo, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
|Date of Submission||23-Jan-2019|
|Date of Acceptance||11-Sep-2019|
|Date of Web Publication||16-May-2020|
Department of Radiotheraphy, Rumah Sakit Cipto Mangunkusumo, Faculty of Medicine Universitas Indonesia, Salemba, Jl. Pangeran Diponegoro No. 71, Kenari, Senen, RW. 5, Kota Jakarta Pusat, Daerah Khusus Ibukota Jakarta 10430
Source of Support: None, Conflict of Interest: None
Introduction: There is limited study comparing dosimetry parameters in detail. In regard to prostate cancer, there are four different techniques, namely three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy-step and shoot (IMRT-SS), IMRT-helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT).
Materials and Methods: Experimental study with intervention on ten prostate cancer patients' computed tomography planning data. 78 Gy dose in 39 fractions was given for planning target volume.Experimental study with intervention on ten prostate cancer patients' computed tomography planning data. 78 Gy dose in 39 fractions was given for planning target volume.
Results: The mean V75 Gy rectum and bladder between 3D-CRT and the other three abovementioned techniques all showed significant results (P < 0.05). V5 Gy remaining volume at risk (RVR) between 3D-CRT versus VMAT and HT, IMRT-SS versus HT, and VMAT versus HT is statistically significant (P < 0.0001). The longest radiation time was done with HT (mean 4.70 ± 0.84 min).
Conclusion: V75 Gy rectum bladder between 3D-CRT techniques differ significantly compared to the three other techniques and may not be suitable to the implementation of escalation doses. The HT technique produced the highest V5 Gy RVR and needed the highest monitor unit amount and the longest radiation duration. The VMAT technique was considered capable of realizing dose escalation in prostate cancer radiotherapy by minimizing toxicity in the rectum and bladder with the shortest radiation duration.
Keywords: Helical tomotherapy, intensity-modulated radiotherapy-step and shoot, prostate cancer, three-dimensional conformal radiotherapy, volumetric-modulated arc therapy
|How to cite this URL:|
Gozal F, Gondhowiardjo SA, Kodrat H, Wibowo WE. Dosimetric analysis of three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric modulated arc therapy in prostate cancer radiotherapy. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 20]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=284490
| > Introduction|| |
Currently, there are several modalities in the management of prostate cancer including surgery, hormonal therapy, and radiotherapy. Radiotherapy (in the form of external radiation and brachytherapy) plays an important role in the management of prostate cancer. External radiation techniques which can be used for prostate cancer include three dimensional-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) in the form of IMRT static (step and shoot [SS]), dynamic (sliding window) and rotational IMRT-helical tomotherapy (HT), and IMRT-volumetric modulated arc therapy (VMAT).,
Recent studies have found that escalation doses of more than 74 Gy in cases of prostate cancer can improve control and reduce recurrence rates but on the other hand can also increase morbidity associated with therapy.,, In response to this, many studies have compared the quality of dosimetry between available radiation techniques in cases of prostate cancer.
Radiation can cause short-term and long-term morbidity caused by radiation exposure to organS at risk (OAR), which in this case, the rectum and bladder. The effectiveness of 2D techniques starts to be questioned when prostate-specific antigen (PSA) testing began to be used to evaluate therapeutic outcomes., An escalation dose is found to give better biochemical control; however, it is done with an increase in radiation-related morbidity and dose exposure to OAR.
Escalation of doses in radiotherapy for prostate cancer up to more than 74 Gy was said to be able to increase the relapse-free survival., There was other study conducted by Pollack et al. which stated that a total increase in dose from 70 Gy to 78 Gy will improve the 6-year freedom from failure from 43% to 62% (P = 0.012) in middle and high-risk prostate cancer patients. The national comprehensive cancer network recommends that the use of doses of 75.6–79.2 Gy with conventional fractions in the prostate (± seminal vesicle) can be given to patients with low risk, while for patients with medium or high risk, dosing of up to 81 Gy will improve disease control (assessed with PSA levels).,, After the discovery of 3D-CRT techniques, it was possible to administer dose escalation on the target without sacrificing the OAR.,,
| > Materials and Methods|| |
This study was an exploratory experimental study by intervening on computed tomography (CT) plan data of prostate cancer patients managed by radiotherapy. The purpose of this study is to understand the differences in dosimetry parameters between 3D-CRT, IMRT-SS, HT, and VMAT radiation techniques. The study was conducted from January 2018 to February 2018. The inclusion criteria are high-risk prostate cancer CT plan. While the exclusion criteria are prostate cancer CT plan postradical prostatectomy, with regional lymph nodes involvement and recurrent prostate cancer.
The CT plan data were collected from the CT plan database backup. The data were made using a GE BrightSpeed CT simulator, GE Health Care with a thickness of 2.5 mm. The CT plan data were transferred to the treatment planning system (TPS) Eclipse External Beam Planning System (Version 13.6, Varian Medical System, California, USA). Delineation of the CT plan for the study sample was done based on guidelines for prostate cancer delineation according to the European Organization for Research and Treatment of Cancer and international commission radiation unit-83.
As for OAR, delineation was done for the rectum, bladder, penis bulb, and femoral head. The remaining volume at risk (RVR) delineation in this study was limited to the entire body volume of patients within 1 cm to the cranial and caudal direction of planning target volume (PTV), without involving clinical target volume (CTV) and OAR. The results of the delineation were verified by a radiation oncologist. The making of planning techniques for 3D-CRT, IMRT-SS, and VMAT was done on TPS Eclipse External Beam Planning System (Version 13.6, Variant Medical System, California, USA). For HT techniques, data delineation was transferred, and planning was made at TPS accuray planning station (V.2.1.0, California, USA).
The dose prescription was 78 Gy in 39 fractions (2 Gy/fraction) on Linac accelerator with 6 MV photon energy. The specification of limitation parameters used in this study include the minimum dose received 95% of the PTV volume was 95% of the prescribed dose (D95% ≥95% dose prescription). The maximum dose received 2% of the PTV volume was 107% of the prescribed dose (D2% ≤107% dose prescription). Not more than 15% of rectal volume received a dose of 75 Gy (V75 Gy rectum ≤15%). Not more than 25% of the bladder volume received a dose of 75 Gy (bladder V75 Gy ≤ 25%). Planning must be made as much as possible to achieve the parameters above. If the entire parameter cannot be reached, the priority will be prioritized to meet the parameter limits for the OAR, either rectum or bladder.
The 3D-CRT radiation technique is made using 5 coplanar directions (0°, 75°, 145°, 215°, and 285°) on axial pieces and MLC-120 millennium variants. The IMRT-SS radiation technique is made using 5 coplanar directions (0°, 45°, 100°, 260°, and 315°) on axial pieces and MLC-120 millennium variants. The VMAT radiation technique uses a single coplanar arc with one rotation during irradiation. Couch is set at an angle of 0°. The angle of the gantry starts at an angle of 181° and stops at an angle of 179°. The size of the field and angle of the collimator are determined automatically through the Eclipse TPS External Beam Planning System to cover PTV as optimal as possible. All three techniques used dosage calculation using Anisotropic Analytical Algorithm with 2.5 mm spatial resolution. The HT radiation technique was made using a 2.5 cm field width, a maximum modulation factor of 3.5, and pitch values between 0.25 and 0.43.15 dosage calculations using convolution/superposition algorithm. Dosimetry parameter data are obtained from the printed dose-volume histogram (DVH) or seen at the TPS. The parameter data analyzed in this study include conformity index (CI), homogeneity index (HI), monitor unit (MU), duration of irradiation, D98% PTV, D95% PTV, D2% PTV and D50% PTV, V75 Gy for rectum and bladder and V5 Gy for RVR. Analysis of the study variables using paired t-test or Wilcoxon was carried out.
| > Results|| |
A total of 10 patients' CT plan data were taken for this study. In [Table 1], it can be seen that the mean age of 10 study participants was 66 years of age. The youngest study participant was 53 years of age; the oldest was 74 years of age. The mean PTV value of the study participants was 395.5 cm3, with the lowest PTV value was at a volume of 251.4 cm3 and the highest was 718.1 cm3.
Comparison of dosimetry average of D2%, D50%, D95%, and D98% planning target volume between three-dimensional technique, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy
[Figure 1] shows the DVH planning results between the four techniques in one sample which illustrates the PTV and the OAR curves. From [Figure 1], it can be seen that the four techniques were able to meet the limitations of the PTV parameters used in the study, but there were differences in ability to reach the limits of the dose parameters for OAR.
|Figure 1: Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric-modulated arc therapy, and helical tomotherapy dose-volume histogram (a) planning target volume, (b) V75 Gy Rectum, (c) V75 Gy bladder, (d) V5 Gy remaining volume at risk|
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[Table 2] shows the analysis results of the mean comparison parameters between D2%, D50%, D95%, and D98%. In the table, D2% value in the 3D-CRT and HT compared with the other three techniques was statistically significant (P < 0.05). The results of the comparison analysis of D50% values listed in [Table 2] shows that significant differences were only found between VMAT technique with the other three techniques. Furthermore, there were no significant differences between D95% mean in 3D-CRT techniques, IMRT-SS, VMAT, and HT.
|Table 2: Mean comparison parameters between planning target volume D2%, D50%, D95%, D98%, V75Gy rectum, V75Gy bladder, and V5Gy RVR|
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[Figure 2] shows the distribution of 95% isodose prescribed dose using 3D-CRT, IMRT-SS, HT, and VMAT techniques. 95% isodose volume from the prescribed dose will be the amount of target volume which will be calculated into the CI as one of the dosimetric parameters analyzed in this study.
|Figure 2: The distribution of 95% isodose prescribed dose using (a) three-dimensional conformal radiotherapy, (b) intensity-modulated radiotherapy-step and shoot, (c) helical tomotherapy, (d) volumetric-modulated arc therapy|
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Comparison of mean dosimetry V75 Gy rectum, V75 Gy bladder, and V5 Gy remaining volume at risk between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy techniques
[Figure 3] shows the distribution of V75 Gy rectum and bladder values and V5 Gy RVR between the four techniques compared in this study. Statistical analysis was performed to assess the mean comparison of the parameters as shown in [Table 2]. The analysis found that the mean V75 Gy rectum between 3D-CRT techniques and the three other techniques showed a statistically significant difference with a value of P < 0.05.
|Figure 3: The distribution of (a) V75 Gy rectum, (b) V75 Gy bladder, (c) V5 Gy remaining volume at risk between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric-modulated arc therapy, and helical tomotherapy|
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[Table 2] shows the results of mean bladder V75 Gy analysis between 3D-CRT techniques and the three other techniques. The result was statistically significant with P < 0.05, P = 0.012, P = 0.007, and P = 0.006, respectively. While between IMRT-SS versus VMAT, IMRT-SS versus HT, and VMAT versus HT techniques, there were no statistically significant differences. [Table 2] above shows significant results (P < 0.05) in the mean V5 Gy RVR between all techniques.
Comparison of monitor unit, conformity index, homogeneity index, mean dosimetry, and mean duration of irradiation between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy techniques
[Table 3] shows the comparison of mean MU, CI, and HI in all four techniques. The MU value distribution between the four techniques is shown in [Figure 4]a. From [Table 3], it was found that the mean MU between 3D-CRT techniques and the other three techniques as well as between HT with the three other techniques showed a statistically significant difference with P < 0.0001.
|Table 3: Comparison of mean monitor unit, conformity index, homogeneity index and beam on time between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step, and shoot, helical tomotherapy, and volumetric-modulated arc therapy|
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|Figure 4: The monitor unit value distribution between (a) monitor unit, (b) conformity index, (c) homogeneity index, (d) beam-on time between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric-modulated arc therapy, and helical tomotherapy|
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Furthermore, the mean CI analysis on the four techniques indicated that the mean CI between 3D-CRT versus IMRT-SS, 3D-CRT versus VMAT, IMRT-SS versus HT, and VMAT versus HT techniques showed statistically significant differences with P < 0.0001. While the mean CI between 3D-CRT versus HT (P = 0.077) and IMRT-SS versus VMAT (P = 0.06) technique was not statistically significant. The distribution of CI values among the four techniques is shown in [Figure 4]b.
[Figure 4]c shows the distribution of HI values between the four techniques. An analysis for the comparison of the mean HI value was also made, where the mean HI between 3D-CRT versus IMRT-SS and VMAT techniques was statistically significant (P = 0.02 and P = 0.006, respectively). [Figure 4]d shows the beam on time in all four techniques, with HT techniques seen to have the longest beam on time. [Table 3] shows the comparative analysis of beam on time between the four techniques and shows that there was a significant mean difference between the four techniques.
| > Discussion|| |
The result of this research showed that the four radiation techniques used provide a good and clinically acceptable absorbed dose distribution (to meet the planning requirements). This can be seen from the mean value of D95%, D2%, and D50% on PTV. In this study, D95%≥95% dose prescribed, D50%>100% dose prescribed, and D2%≤107% dose prescribed parameters were used.
Difference in rectum and bladder volume which received doses of 75 Gy (V75 Gy) and volume of remaining volume at risk that receives doses of 5 Gy (V5 Gy) between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy techniques
The data in [Table 2] shows that there was a significant difference between V75 Gy rectum and V75 Gy bladder between 3D-CRT technique with IMRT-SS, VMAT, and HT techniques. This is consistent with a study conducted by Uysal et al. which compared dosimetry parameters between IMRT and 3D-CRT where V60 Gy rectum (P = 0.001) and V60 Gy bladder (P = 0.001). This condition can be caused by the number of segments which can be more exposed in the IMRT technique (IMRT-SS, VMAT, and HT) when compared with 3D-CRT techniques, which will give less exposure to critical organs, especially the rectum and bladder.
Unlike the 3D-CRT technique, other modern techniques such as IMRT-SS, VMAT, and HT can meet the recommended dose limits for rectum and bladder while still providing a good dose distribution to PTV with no significant differences [Table 2]. This result is in line with the study conducted by Pasquier et al. and Davidson et al. where the mean V75 Gy rectum and bladder in the HT technique were slightly higher than the VMAT technique, but the difference was not significant; thus, it can be said that the VMAT and HT techniques were able to provide results which is almost equal in sparing doses., Leszczyński et al. in their study also stated that both IMRT and RapidArc have high conformity dose distribution abilities with OAR sparing as well.
Furthermore, in this study, V5 Gy RVR was also assessed to determine low-dose radiation exposure in normal tissue in the radiation field. The highest V5 Gy RVR was in HT technique (99.94 ± 0.09). Rotational techniques owned by VMAT and HT have an impact on the high low-dose radiation exposure to all normal tissues in the radiation field. It is known that the risk of radiation-induced malignancy is influenced by scatter dose, MU value, and normal tissue volume-receiving low-dose radiation. It is known that the risk of secondary malignancy increases 0.4%, 1.0%, and 2.8% in the use of conventional radiation techniques, IMRT-SS, and HT.
The difference of monitor unit and radiation duration between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy techniques
This study shows a significant difference of MU values in almost every technique (P < 0.05) except between IMRT-SS versus VMAT techniques (P = 0.28). The insignificant difference between the MU scores of the IMRT-SS and VMAT techniques in this study is not in accordance with the results of other studies by Leszczyński et al. and Hardcastle et al. who obtained P < 0.05 and P < 0.01, respectively., This difference in results can be due to differences in the amount and direction of the rays used in the other two studies, where Leszczyński et al. used 7-way rays and Hardcastle et al. used 7–10 directions of noncoplanar rays.
The highest MU amount with the HT technique obtained from this study has an impact on the need for a long radiation duration (mean 4.70 min ± 0.84). This is consistent with the theory that increasing MU will increase the duration of radiation needed., It was also said that the high radiation duration will increase the risk of changes in geometric position and organ movement during radiation. These changes will have an impact on the accuracy of radiation targets and will indirectly increase the risk of radiation-induced malignancy.
The difference between conformity index and homogeneity index between three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric-modulated arc therapy techniques
In this study, the best CI value was obtained by planning using the VMAT technique, where the CI values of VMAT and HT techniques were considered to have significant differences, but the difference between VMAT versus IMRT-SS techniques was not significant. Davidson et al. in their study also found that VMAT provides superior conformity compared to IMRT and HT techniques. CI and HI are indicators in treatment planning which are widely used to analyze a CRT plan. Dose homogeneity can be used as a parameter to assess the uniform distribution of doses within a target volume, while dose conformity can be defined as a comparison between the irradiated volume with PTV.
The results of this study showed that the CI value in the HT technique was quite high, and this result was different from the results of other studies, including the study by Tsai et al. with the lowest CI index was in the HT technique (1.3). Study conducted by Tsai et al. found significant differences between CI values of HT techniques with VMAT and IMRT. This may be due to a difference in PTV volume between smaller samples size (mean 104.89 ± 20.2 mL) compared to PTV in this study (mean 395.5 ± 162.4 mL).
Significant differences were obtained between HI 3D-CRT values with IMRT-SS and VMAT techniques, while HI comparisons between other techniques were not considered significant. This study found that the HI values between HT techniques were almost equal with 3D-CRT techniques (mean 0.09 ± 0.03 and 0.11 ± 0.04) with insignificant differences. It can be said that the dose homogeneity with the HT technique is almost equal to the homogeneity which can be achieved with 3D-CRT techniques. Iori et al. in their study also concluded that the HT technique has advantages in terms of dose homogeneity and target coverage compared to VMAT techniques. Another study by Davidson et al. compared the VMAT, HT, and IMRT techniques and also concluded that HT provides a more homogeneous dose distribution despite higher integral doses.
| > Conclusion|| |
This study finds significant difference between D2% PTV 3D-CRT with 3 other techniques. (IMRT-SS, VMAT and HT). Significant differences were also obtained between D50% VMAT PTV compared to 3 other techniques and PTV D98% between HT and IMRT-SS. However, overall, the four techniques were able to provide a good distribution of absorbed dose and can be accepted clinically to meet the planning requirements.
The V75 Gy rectum (61.22 ± 18.80) and bladder between 3D-CRT techniques (50.17 ± 29.32) differ significantly compared to the three other techniques. This increase in V75 Gy, implies that 3D-CRT techniques may not be suitable for prostate cancer escalation doses, as it shows higher toxicity concerns.
The ability of sparing doses on critical organs and the dose homogeneity obtained in the HT and VMAT techniques showed no significant different results. However, HT technique has inferior conformity compared to VMAT technique. The HT technique produced the highest V5 Gy RVR and needed the highest MU amount and the longest duration of radiation, which were significantly different compared to the other 3 techniques.
The VMAT technique was considered capable of realizing dose escalation in prostate cancer radiotherapy by minimizing toxicity in the rectum and bladder. The shortest radiation duration using the VMAT technique was significantly different compared to the other 3 techniques.
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Conflicts of interest
There are no conflicts of interest.F
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]