Introduction
Helical tomotherapy is a novel treatment approach that combines Intensity-Modulated Radiation Therapy (IMRT) delivery with built-in image guidance using megavoltage (MV) CT scans. The unit also allows the acquisition of MVCT images using the same radiation source detuned to reduce its effective energy to 3.5 MV.Reference Yartsev, Kron and Van Dyk1 The daily MVCT images are used in verifying daily setup before treatment to improve target localisation accuracy. Some patients, however, have significant daily anatomical changes, especially in prostate cancer, in which different filling conditions of the bladder and rectum can significantly influence the inter-fraction position of the prostate.Reference Huang, Dong and Chandra2–Reference Wu, Haycocks and Alasti3 Consequently, the patient receives an actual dose different from the planned dose.
Deformable image registration (DIR) is the process which can be used to modify the structure according to anatomical changes for observing dosimetric effect. DIR attempts to register the different patient anatomy’s image data sets into a reference image data set and determine the minimised differences between the two image sets by identifying the spatial correspondence.Reference Oh and Kim4 The deformable images that were created can be used to recalculate actual target and OARs dose received. Therefore, this method can evaluate the difference in accumulated dose from the initial planned dose in each fraction. In this study, daily MVCT images from helical tomotherapy were used to generate a cumulative dose with a DIR method for prostate cancer. The daily cumulative doses were analysed to assess the variations from the initial plan.
Material and Methods
Patient characteristics
A retrospective randomised study of five prostate cancer patients who were treated with a helical tomotherapy unit (TomoTherapy, Inc., Madison, WI, USA) at the Radiation Oncology Division, Maharaj Nakorn Chiang Mai Hospital was carried out. All patients underwent IMRT with prescribed dose of 70 Gy in 28 fractions delivered to the planning target volume (PTV) following the RTOG 0415.Reference Lee, Dignam and Amin5 This study was granted an ethics exemption by the Institutional Review Board of Faculty of Medicine Chiang Mai University (study code RAD-2561-05828/Research ID: 5828)
Daily MVCT image acquisition
One hundred and forty MVCT images of the pelvis were acquired by using the helical tomotherapy unit. In an effort to ensure reproducible bladder filling, all patients received instructions to follow the bladder preparation protocol by empty their bladder, then drink 200 mL of water and wait for 25 min before the planning CT scan and prior to each day of treatment. Patient image alignment used a matrix of 512 x 512 with voxel dimension of 0.7634 mm3 × 0.7634 mm3 × 3 mm3. The daily MVCT scan range must cover the entirety of the PTV, bladder and rectum. In cases where the image did not cover all of them, the data from the closest day were used.
Deformable image registration
MIM software (MIM Software Inc., Cleveland, OH, USA) was used to create the deformation vector field (DVF) with Free-Form Deformable Registration algorithm.Reference Broggi, Scalco and Belli6 The planned kVCT images were acting as the source images and daily MVCT were acquired as the target images for registration. The automatic deformed structure was used to access the volume variation and daily dose accumulation to each structure.
Assessment of accumulated dose
The daily dose deformation values were summed to the accumulated dose and compared to the initial planned dose distribution. Regarding the PTV70, the median absorbed dose (D50%), the near-minimum (D98%) absorbed dose, and the near-maximum (D2%) absorbed dose values from each fraction were assessed. The PTV50.4 was assessed by D50% absorbed dose. The rectum and bladder were evaluated by D50%, D35%, D25% and D15%. The bilateral femoral head was assessed by D10%. All of these dose-volume parameters were compared to the initial planned dose.
The normality of the variable distribution was verified using the Shapiro–Wilks test. Paired sample t-test was performed for normal variable distributions, while the Wilcoxon signed-rank test was performed for non-parametric statistics using version 23 of the SPSS statistical program. Both test metrics were compared metrics to determine the statistical significance on each data set, with a threshold of p < 0·05.
Results
ROI volume variations
The targets volume were decreased by an average of 2·8% ± 2·83 (PTV70) and 13·5% ± 6·96 (PTV50.4) at the end of the treatment course.
For the OAR, the average volume of rectum was decreased by 15·7% ± 5·76 at the end of the treatment course. However, the bladder volume increased by an average of 53·5% ± 12·58 from the initial plan.
Accumulated dose variation from initial planned dose
The accumulated dose of PTV70 decreased on with an average 1·0 ± 0·67% (D50%), 6·3 ± 3·95% (D98%) and 1·4 ± 0·42% (D2%) at the end of the treatment. The D50% of PTV50.4 lower than the initial planned dose was 2·1 ± 1·54%. Figure 1 demonstrates the daily target dose variation of PTV70 and PTV50.4. The median dose variation was significantly different from the initial planned dose after three fractions of treatment (p = 0·021). However, the median dose of PTV50.4 was significantly different after 11 fractions of treatment (p = 0·027).
Figure 1. Daily accumulated dose and percentage of dose differences. Comparison between planned dose and deformable dose for median dose, D50% of (A) the planning target volume prescribed of 70 Gy dose (PTV70) and (B) the planning target volume prescribed of 50.4 Gy dose (PTV50.4) including (C) near-minimum dose, D98% and (D) near-maximum dose, D2% of PTV70.
Figure 2 illustrates the dose distribution for the rectum and bladder at the 28th treatment fraction compared with the initial plan. The rectum dose increased more than the initial planned dose by 2·1 ± 9·01% (D50%) and 1·2 ± 8·64% (D35%), However, D25% and D15% were decreased from the initial plan by 0·6 ± 7·18% and 2·4 ± 5·43%, respectively. Figure 3 illustrates that the dose variations were significantly different from the initial plan after ten fractions of treatment with p = 0·028 and 0·033 for D25% and D15%, respectively. D50% and D35% were not significantly different from the initial plan.
Figure 2. The dose distribution for bladder (green line contour) and rectum (yellow line contour) for the initial planned dose on kVCT image (left) and accumulated dose at the 28th fraction’s MVCT image (right).
Figure 3. Daily accumulated dose and percentage of dose difference comparison between planned dose and deformable dose of the rectum for (A) D50%, (B) D35%, (C) D25% and (D) D15%.
Figure 4 demonstrates D50%, D35% and D25% of the bladder were increased from the initial plan by 5·1 ± 7·68%, 3·2 ± 6·05% and 1·8 ± 4·35%, respectively. However, D15% was lower than the initial plan by 0·3 ± 2·87% at the end of the treatment. This was significantly different from the initial plan after 11 fractions of treatment (p = 0·019).
Figure 4. Daily accumulated dose and percentage of dose difference comparison between planned dose and deformable dose of the bladder for (A) D50%, (B) D35%, (C) D25% and (D) D15%.
D10% for the left head of the femur was significantly increasing from the initial plan after 21 fractions (p = 0·043) by an average of 6·2 ± 5·87% at the end of treatment (Figure 5). However, the dose of right femoral head was decreased by an average of 0·2 ± 6·04% at the end of the treatment and not significant for throughout the treatment course.
Figure 5. Daily accumulated dose and percentage of dose difference comparison between planned dose and deformable dose for D10% of (A) left head of femur and (B) right head of femur.
Discussion
The variation of the bladder volume shows the highest increase of approximately 50% from the initial plan. This result was possibly caused by the physiologic processes or the different duration of patient preparation between pre-simulation and pre-radiation procedures. Moreover, the daily bladder volume had changed throughout the treatment course, as shown by standard deviation values that were as high as 12·6%. However, Pinkawa et al. Reference Pinkawa, Asadpour, Gagel, Piroth, Holy and Eble7 demonstrated the variability of bladder filling does not affect the prostate position with a full bladder when comparing with an empty bladder.
As regards the accumulated dose variation, the D50% and the D2% of the target varied from the initial by planned less than 2%. Nevertheless, D98% was varied greater than 5%. These results were consistent with Godley et al.,Reference Godley, Ahunbay, Peng and Li8 where D95% and D100% of the target were decreased from the initial plan by an average of 3·6% and 6%, respectively. In addition to the bladder and the rectum, the accumulated dose tended to increase from the initial plan, except the D15% of the bladder and D15%, D25% of the rectum. Our study showed a decrease from the initial plan at the end of treatment.
In each fraction of the treatment, the target and high-dose regions of OAR were significantly different between the dose from initial plan and deformable dose. The slight volume changes in the high-dose area, especially the target volume, can affect numerous dose variations, as seen from the deformable dose of the target, which was significantly different from the initial planned dose during the first period of treatment.
The results of this study demonstrate the difference between the actual dose and planned dose throughout the treatment. These effects result in the effectiveness of radiotherapy treatment in terms of decreased tumour control probability and increased normal tissue complication probability. Therefore, the DIR methods should be used for adaptive treatment strategies in clinical implementation to improve outcome.
The purpose of this study is to assess the daily cumulative doses. However, this study is a retrospective study. In some image sets, the MVCT scan range did not cover whole targets, bladder or rectum. The problem was resolved by selecting the image from the closest day for the cumulative dose summation. To decrease the effect to the study results, we allow to use only the image from the closet day. If the patient’s image cannot be used more than two consecutive days, that patient will not be included in this study. In addition, another limitation of this study is the small number of patients, which is too small to draw any solid conclusions. Therefore, these limitations should be considered to define the daily image scan range and increase the sample size in a future prospective study.
Conclusion
The daily accumulated dose was evaluated with DIR software. Due to the patient’s anatomical changes, the daily actual dose differed from the initial planned dose. The accumulated dose of target tends to be lower than the initial plan, while rectum, bladder and bilateral femoral head were higher than the initial plan. Therefore, The DIR methods on Helical tomotherapy MV images showed clinically useful information for observation as a result of inter-fractional anatomic changes and beneficial for adaptive treatment strategies.
Author ORCIDs
Warit Thongsuk 0000-0002-8350-1518, Imjai Chitapanarux 0000-0002-8552-0149, Somsak Wanwilairat0000-0003-0165-2513, Wannapha Nobnop 0000-0002-5266-2845
Acknowledgements
The author offers many thanks to TransMedics (Thailand) Co. Ltd. for supporting MIM software.
Financial Support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Conflicts of Interest
None.
