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Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion
Medical Dosimetry 38 (2013) 359–365
Medical Dosimetry journal homepage: www.meddos.org
Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion Eunhyuk Shin, Ph.D.,n† Youngyih Han, Ph.D.,n Hee-Chul Park, M.D., Ph.D.,n Jin Sung Kim, Ph.D.,n Sung Hwan Ahn, Ph.D.,n Jung Suk Shin, M.Sc.,n Sang Gyu Ju, Ph.D.,n Doo Ho Choi, M.D., Ph.D.,n and Jaiki Lee, Ph.D.† Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and †Department of Nuclear Engineering, Hanyang University, Seoul, Korea
n
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 June 2012 Accepted 20 April 2013
This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution. & 2013 American Association of Medical Dosimetrists.
Keywords: Tomotherapy Moving tumor Intensity-Modulated Radiation Therapy 4-Dimensional radiation therapy
Introduction State-of-the-art radiation therapy, such as intensity-modulated radiation therapy (IMRT) and volumetric modulation arc therapy, has made radiation therapy significantly less prone to previously common complications,1-3 while enabling significant dose escalation by reducing critical organ dose in treatment. Helical tomotherapy is one such method of IMRT in which an x-ray source rotates around the patient, who is positioned on a couch that moves
Reprint requests to: Youngyih Han, Department of Radiation Oncology, Samsung Medical Center, #50, Irwon dong, Kang nam gu, Seoul, Korea. Tel.: +82 2 3410 2604; fax: +82 2 3410 2619; or Hee-Chul Park, Department of Radiation Oncology, Samsung Medical Center, #50, Irwon dong, Kang nam gu, Seoul, Korea. Tel.: +82 2 3410 2605; fax: +82 2 3410 2619. E-mails: [email protected], [email protected]
continuously into the gantry. A high level of intensity modulation can be achieved in this method by controlling each multileaf collimator (MLC) leaf's on-off period together with couch translation and gantry rotation speeds. It has been demonstrated that tomotherapy is more effective in regulating target conformity and normal tissue sparing compared with other conventional techniques.4,5 However, when treating a moving organ with tomotherapy, several issues remain owing to the aforementioned dynamic nature of the treatment. Previously, studies, both theoretical and experimental, have investigated the interplay of tumor motion and dynamic characteristics of treatment, such as gantry rotation period, pitch, jaw size, and MLC motion, and found that unwanted longitudinal dose modulation and symmetric and asymmetric dose blurring can occur in the treatment region for only single fraction.6-8 Unwanted dose modulation creates 2 unwanted effects: an underdose and overdose to the target region and an overdose to
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nearby normal tissues. Expanding the margin in forming the planning target volume (PTV) may compensate for underdosing in peripheral regions of a target. However, this does not fully address the dose variation (inhomogeneity) inside the target that arises from the interplay between target motion and the machine parameters. Previous studies4,9,10 have reported that dose inhomogeneity in the target varies with the relative quantities of speed of tumor vs MLC leaf motion, and the width of leaf gap vs the tumor motion amplitude. Therefore, the effects of anatomic motion and machine dynamic on treatment must be more fully understood in using tomotherapy for treating moving tumors. One widely used remedy for tumor motion in radiation therapy is the gating technique, which irradiates radiation synchronized with patient breathing. However, because of the helical nature of the treatment, this technique is not currently applicable to tomotherapy. Nonetheless, repetition of treatment for several fractions possibly lessens the underdosing or overdosing in the tumor. The cumulative effect of this practice does potentially reduce the error shown in previous studies that analyzed motion effects for one fraction on treatment.11,12 However, the effects of this practice on surrounding normal tissue are unclear and may potentially erase any compensatory effect it may have. This lack of quantitative data increases the risk associated with tomotherapy treatment for a moving organ and thus limits its applicability. This study was designed to evaluate this cumulative error in a moving target and nearby normal tissues. Specifically, the dose variation was assessed in the peripheral and central regions of the target as well as the nearby area of normal tissue for various target motions and plan parameters.
Methods and Materials Design of a moving phantom To perform dosimetry analysis in accordance with organ movement, we designed a 2-dimensional moving phantom in which motion could be programmed. The moving phantom consisted of a phantom imitation of a human thorax, a motor, and a software to control the motor. The software was designed to adjust the amplitude and period of motion in the form of a sine wave using LabVIEW 7.0 (National instrument). This program enabled us to store absolute position data of the phantom in each point of time. The positional error of the motion phantom is within 0.1 mm in 85% of the tested time, and time delay is within 0.1 second as shown in Fig. 1. The human model phantom was created by modifying an I'mRT phantom (Scanditronix-Welhoffer, Schwarzenbruck, Germany). To display the clinical target volume (CTV), acrylic material was used in making the phantom insert, as shown in Fig. 2A. The phantom insert was made of LEGO-type blocks that were 160 55 mm and 40 25 mm in size. The target shape and organ at risk (OAR) were designed to be sensitive to the craniocaudal motion. The horseshoe shape on the coronal plan was specifically selected to situate the OAR between the 2 wings, thereby affected by craniocaudal motion. Radiation treatment planning For the static-state phantom, computed tomography scans were taken using a 16-slice computed tomography scanner (LightSpeed RT16: General Electric Healthcare, Waukesha, WI). All acquired data were transferred to a tomotherapy planning software (TomoTherapy, Madison, WI), and several different plans were generated using various clinical treatment parameters, including jaw size, pitch, and modulation factor. The horseshoe-shaped CTV was on a coronal plane, and the outer dimension of the target was 9 9 cm2. An OAR was situated between the 2 wings of the horseshoe. The OAR had the shape of a rhombus on a coronal plane and a circle on a transverse plane and is shown in Fig. 2C. PTV was defined by adding a margin of 2 mm to the posterior direction and 5 mm to other directions. Treatment plan is generated with various planning parameters. The clinically preferred planning parameters such as field size 1.05 cm, pitch 0.287, and modulation factor 1.5 in tomotherapy are chosen as the standard. Additional treatment plans were prepared with changing field size 2.5, pitch 0.660, and modulation factor 2.5 as summarized in Table 1A. The 1.49 Gy per fraction was prescribed to 95% volume of the PTV to prevent film saturation in multiple exposures. The mean dose of the OAR and the maximum dose were constrained not to exceed 40% and 70% of the prescribed dose with each planning parameter, respectively.
Fig. 1. (A) Comparison of input signal to the phantom and phantom motion detected by RPM. Patient's respiration signal was used as input signal. (B) In 99.9%, 2 signals showed good agreement within 2 mm. (Color version of figure is available online.)
Tomotherapy delivery This study focused on a solid tumor in which nonrigid motion can be ignored. To investigate the motion effects for different motion parameters, measurements were taken for various periods and amplitudes. Two different motion patterns, a sine function pattern and a pattern using motion data acquired from a RPM signal of a real patient who was on respiratory training, were tested and compared with static cases as shown in Table 1B. To investigate the cumulative doses delivered over multiple fractions with respiration motion, tomotherapy plans were delivered from 1 to 5 fractions (from 1.49 Gy to 1.49 5 ¼ 6.5 Gy) in each film using GAFCHROMIC EBT-2 of the same batch number. To reduce uncertainty due to phantom position, multiple tomotherapy irradiations were performed in each experimental session without resetting the phantom. The beam delivery was started at random phase of the phantom motion to mimic real treatments. Dose distributions were measured and compared with that obtained for static phantom. Two-dimensional analyses were performed for a period of 4 seconds and amplitude of 2-cm data.
Dosimetry analysis We performed gamma index comparison between 1 fraction of irradiated film in a static phantom and computed dose distribution using the tomotherapy treatment planning system. Other comparisons using gamma index were also performed to determine interfractional change in dose distribution. The dose difference between multiexposures was found by comparing static-state dose distribution with 1-time exposure, 1- and 2-, 2- and 3-, 3- and 4-, and 4- and 5times exposure. For quantitative comparisons, each pixel value for nth multiexposure film was multiplied by (n + 1)/n for normalization and compared with (n + 1) multiexposure data. Additional dose distribution analysis was performed on the profiles intersecting the OAR center and target region. The penumbra width, minimum and maximum values of profiles, and full-width half maximum were measured. These quantities are related to dose variation in the target and OAR regions. Each test was performed 3 times to ensure our tests could be reproduced.
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evaluation of the target DAH, the underdose area (UDA) and overdose area (ODA) depicted were defined as follows: Dose area of underdose for moving Fxx Dose Area of underdose for static condition
UDA ¼
ODA ¼
Dose area of overdose for moving Fxx Dose Area of overdose for static condition
The dose area of OAR (DAO) is defined as follows: DAO ¼
Dose area of whole OAR for moving Fxx Dose Area of whole OAR for static condition
Results Dosimetry analysis
Fig. 2. Configuration of (A) a human-modeled phantom design front view of the phantom, (B) its inserted material, and (C) CTV and OAR in the experiment. (Color version of figure is available online.) Histogram-based (dose area histogram [DAH]) analysis For the target and OAR, a DAH was computed to measure CTV coverage at each multiexposure. To do this, a template for defining the target and OAR regions was applied in the process of film analysis. Every point of the target region was converted to a dose. Following this, the dose of each pixel and the total number of pixels inside the target and OAR regions were calculated. For quantitative
Table 1 Various (A) planning parameter and (B) respiration parameter used in this study (A) Plan name
Field width
Pitch
Modulation factor
Plan Plan Plan Plan
1.05 1.05 2.5 1.05
0.660 0.287 0.287 0.287
1.5 1.5 1.5 2.5
0 1 2 3
The data measured in a static phantom were in agreement with treatment planning predictions in 98.81% of the tested regions within gamma index criteria (3%/3 mm) for plan 0. The 1.19% of deviation includes setup error, machine output error, and film dosimetry uncertainty. Especially film dosimetry uncertainty was minimal. Measured data in a moving phantom exhibited large deviation, as summarized in Table 1B and Figs. 3 and 4. As shown in Figs. 3 and 4, for all tested plans, the deviation between multiexposure decreased as the treatments were further processed. As shown in Table 2A, the gamma index comparison for 1time exposure of treatment in a moving phantom and the static case failed to meet 3%/3 mm criteria in 39.05% to 28.80% of the tested area. However, from comparison of the 2-times and 1-time exposure, gamma indexes were greater than or equal to 1 in 16.34% to 9.19% of the region. In the 3-times exposure, the region over 3%/3 mm difference was almost saturation (2.57% to 9.33%). For 4-times exposure, the gamma value compared with 3-times exposure failed to meet the criteria in approximately 3% (1.14% to 3.47%) of the region. The 5-times exposure deviation was observed in less than 3% (0.69% to 2.21%) of the tested area. The total accumulated deviation is shown in Table 2B. The largest deviation was 22.14% in plan 0, followed by plan 3 (19.06%) and plan 1 (16.24%). The smallest deviation was observed in plan 2 (12.03%). Dose profiles along the cranial-caudal direction passing through the target and OAR were obtained for each multiexposure. For side-by-side comparison, each profile was multiplied by 5/n for nth times exposure. As already shown in the gamma index, the profile shape of plan 0 showed a large deviation from the static profile in the 1-time exposure of treatment. However, in the 4- and 5-times exposure, the profile shapes became very similar to each other. The observed phenomena are reproducible, as the 3 different measurements of 5 accumulated fractions exhibited the very similar profiles as shown in Fig. 5.
(B) Mode
Amplitude (cm)
Period (s)
Sine Sine Sine Sine Sine Irregular
1 4.0 2 4.0 3 4.0 2 3.0 2 5.0 Real patient respiration motion (about 2 cm, 4 s)
Fig. 3. Lateral profiles crossing OAR of treatment plan 1. (Color version of figure is available online.)
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Fig. 4. Gamma analysis for plan 0 (A) static vs 1-time exposure, (B) 1-time exposure vs 2-times exposure, (C) 2-times exposure vs 3-times exposure, (D) 3-times exposure vs 4-times exposure, and (E) 4-times exposure vs 5-times exposure. (Color version of figure is available online.)
Histogram-based Analysis
Fig. 5. Reproducibility test for treatment plan 0. (Color version of figure is available online.)
The accumulated effects of the multifractional treatment for plan 1 are presented as a DAH in Fig. 6. In Fig. 6, it can be seen that the largest dose deviation in both target and OAR was at the 1time exposure. From the 3-times exposure and on, the DAH moves closer to the static case rather than deviate further from the static curve. In Fig. 6 A and B, DAH of target and OAR at 4- and 5-times exposure is very similar to each other and eventually converge. In Table 3A, the normalized ratio of the UDA for 1-time and 2times exposure of plan 1 was 1.87 and 1.86, respectively. From the 3-times exposure, the ratio remained at 1.78. The ODA of DAH for the 1-time exposure was 1.38; however, the value was reduced to 1.22 from the 2-times exposure. In Table 3B, the UDA and ODA of the 1-time exposure are normalized to the static values and summarized for different treatment parameters. For the 4-second motion period, 3 cm of
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n (γ 4 1)
Plan 0
Plan 1
Plan 2
Plan 3
RTP and static Static and fx 1 fx 1 and fx 2 fx 2 and fx 3 fx 3 and fx 4 fx 4 and fx 5
1.19 37.71 16.34 9.33 3.47 2.21
1.81 28.80 9.19 4.71 3.26 1.93
1.69 39.05 13.45 2.57 1.14 0.69
1.99 36.76 17.13 6.77 3.42 1.91
motion was observed. However, deviation did vary between plans; plan 2, which used a larger field width than other plans, showed a smaller increment of cold region in the target compared with other plans. In addition, in a comparison of plans 1 and 3, plan 3, which had the higher modulation, showed a larger deviation. As presented in Table 3C, irregularity of the motion period slightly increased the ODA of DAH. The UDA in plan 2 did increase but was still approximately equivalent to that of regular motion for plans 1 and 3. The dose at the center of the OAR was not particularly affected by period of motion, but rather, the dose at the center of the OAR increased as motion amplitude became larger. The OAR dose increment had a positive linear relationship with the increment of penumbra size at the boundary of the target.
Plan 0
Plan 1
Plan 2
Plan 3
Discussion and Conclusions
32.33 26.77 22.50 21.14 22.14
24.4 19.24 15.02 15.46 16.24
35.26 23.64 15.21 11.68 12.03
26.29 20.76 18.66 17.06 19.06
In this study, we experimentally verified that dose distortion due to organ motion increased up to 2 to 3 times exposure, and after 3-times exposure, dose distributions in the target and OAR converged to a constant distribution. The phenomenon was verified through the gamma index test, DAH shape, DAH change, and dose at the center of the OAR (Figs. 3 and 4 and Tables 2 and 3). This is potentially owing to that the out- or in-phase deviation between the tumor motion and gantry rotation was maximally affected in the 1 to 2 fractions of treatments. Distortion levels inside the target were affected by motion parameters; larger motion amplitude and a larger motion period resulted in increased dose distortions, caused in part by extended penumbra size at the peripheral region of the target (Table 2B). In contrast, dose at the center of the OAR was affected rather by motion amplitude than motion period (Table 1B), and dose increment at the center of the OAR was caused by extended penumbra
Table 2 Percentage of area with gamma index value 41 during sine respiration mode, compared with (A) the previous fraction and (B) static isodose (amplitude 2 cm and period 4 second) RTP means planned dose distribution, and static means film measurements for static phantom (A)
(B) n (γ o 1) Static Static Static Static Static
and and and and and
fx fx fx fx fx
1 2 3 4 5
RTP (TomoTherapy Hi-Art ver. 4.2, Tomotherapy, USA); fx = repeat number of fraction.
motion amplitude caused the largest increase in UDA and ODAs, which were 2.37 and 2.48, respectively. For 2-cm amplitude of motion, the 5-second period resulted in a larger UDA/ODA of DAH compared with the 4 second or 3 second periods, which were 2.23/ 1.76, 1.87/1.38, and 1.81/1.15, respectively. DAH for regular motion and irregular motion for the 2-cm amplitude and 4-second period of motion is compared in Table 3C. No significant difference between regular and irregular
Fig. 6. DAH (dose area histogram) analysis of convergence for plan 1 (pitch 0.287, jaw width 1.05, and modulation factor 1.5) (motion amplitude 2 cm and period 4 second) (A) for target and (B) for OAR. (Color version of figure is available online.)
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Table 3 UDA (underdose area) and ODA (overdose area) and OAR area normalized static condition for (A) passing on the number of treatments in plan 0 (amplitude 2 cm and period 4 second), (B) various moving parameters, and (C) various plans and irregular motion (A)
Fx Fx Fx Fx Fx
1 2 3 4 5
UDA (target)
ODA (target)
Area (OAR)
1.87 1.86 1.78 1.78 1.78
1.38 1.22 1.22 1.21 1.23
1.40 1.33 1.33 1.26 1.25
(B)
4s 4s 4s 5s 3s
2 cm 1 cm 3 cm 2 cm 2 cm
UDA (target)
ODA (target)
Area (OAR)
1.87 1.08 2.37 2.23 1.81
1.38 1.03 2.48 1.76 1.15
1.40 0.96 1.49 1.21 1.20
(C) UDA (target)
ODA (target)
Area (OAR)
Plan 0
Regular Irregular
2.01 2.02
1.75 1.76
1.34 1.35
Plan 1
Regular Irregular
1.55 1.55
1.42 1.46
1.31 1.28
Plan 2
Regular Irregular
1.42 1.46
1.58 1.60
1.20 1.21
Plan 3
Regular Irregular
2.59 2.58
1.49 1.52
1.31 1.29
size owing to motion amplitude. Analysis of DAH changes in Table 3 suggests irregularity of motion not to be a significant factor in dose distortion compared with other motion parameters and plan complexity. Regarding plan complexity, the more complicated plan with the larger modulation factor (2.5: plan 3) resulted in larger dose deviation than the plan with a modulation factor of 1.5 (plan 1) over the static case (Table 3C, plan 3 vs plan 1). The observed phenomenon is thought to be reproducible because 3 different measurements of an accumulated 5 fractions of treatments showed very similar trends (Fig. 5). Bortfield et al.11 used statistical analysis to investigate dose distributions in a moving organ treated with IMRT with linear accelerators and concluded that dose distribution after several fractions was close to the Gaussian around the expected value. In addition, with 5-mm amplitude of organ motion for 30 fractions of treatments, the standard deviation was within 1% of the expected value. Although this current study investigated tomotherapy for a moving organ, the convergence of dose distribution after 2 to 3 fractions is thought to be in agreement with their findings, and several similarities can be found. As in the Bortfield study, we found a large dose difference for the initial 2 to 3 fractions. However, in our study, the deviation appears to be significantly larger. This is potentially owing to the smaller target volume and closely situated OAR position to the target. Using simulation studies, Kissick et al.13 investigated the effect of irregularity of a patient's breathing on the dose distribution along the cranial-caudal direction. They reported that the random breathing amplitude relative to jaw size has a linear relation to
dose error probability. While for regular breathing motion, when random error effects were not expected, and if the peak-to-peak amplitude of the target motion is smaller than the jaw size, the unwanted dosimetric error was negligible. However, we did not observe the same effect, potentially owing to the difference in target geometry, which was very narrow, compared with jaw size in the cranial-caudal direction. In our study, all regular breathing motions caused dose distribution errors, even when the motion amplitude was smaller than jaw size. Compared with the theoretical study by Kim et al.,7 which reported 3 different types of motion-induced artifacts, dose rounding effects were more clearly observed in our experiments. Dose riffling artifacts caused by dose redundant in tomotherapy were larger for longer periods of target motion. Regarding machine parameters, the largest jaw size (plan 2) minimized the deviation. For the same jaw size, a smaller modulation factor plan showed less deviation (plan 1 vs plan 3). For the same jaw width and modulation factor, a smaller pitch showed less dose distortion (plan 2 vs plan 1) (Table 2). Our findings are in agreement with those of previous studies by Chaudhari and Goddu2 and Song et al.,14 which reported that larger jaw width relative to the motion amplitude and low couch speed (smaller pitch) reduced the motion-induced error. To overcome motion-induced artifacts, several suggestions have been proposed in recent years. One such strategy has been motion-adaptive beam delivery on static and dynamic15,16 gantry motions. This method rearranges the projections and leaf indexes of preprogrammed leaf sequences (sinogram) according to instantaneous target position, if the target position can be detected accurately. However, although the method is promising, accurate detection of tumor position is still a challenging issue.17 A realistic method in current stage of tomotherapy is to manage motion amplitude to be small compared with jaw size. For regular breathing motions without drifting effects, dose deviation was predicted to be minimal with acceptably small dose blurring. However, as our results indicate, this strategy is still limited to tumors that are comparably larger in dimension, compared with jaw width. When the tumor size is small, this general rule does not apply. According to our study results, practical use of moving target treatment with tomotherapy requires taking dose-blurring effects into consideration in determining the PTV and requires the selection of a larger jaw size with a low modulation factor. Also, a training program for patients to breathe in small amplitude, short period, and, if possible, regular pattern would be beneficial. In summary, tomotherapy on a moving target causes a large dose deviation in the first exposure; however, within 3 fractions, the deviation converges to some constant value depending on level of plan difficulty. Pretreatment measurements for 3 fractions of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.
Acknowledgments This research was supported by IN-SUNG Foundation for Medical Research and the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science, and Technology (2010-0011771). References 1. Jiang, S.B.; Pope, C.; Al Jarrah, K.M.; et al. An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments. Phys. Med. Biol. 48:1773–84; 2003. 2. Chaudhari, S.; Goddu, S. Breathing motion‐induced dose delivery error evaluations as applied to tomotherapy dose delivery. Med. Phys. 34:2561; 2007.
E. Shin et al. / Medical Dosimetry 38 (2013) 359–365 3. Otto, K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med. Phys. 35:310–7; 2008. 4. Zhang, X.; Penagaricano, J.; Moros, E.G.; et al. Dosimetric comparison of helical tomotherapy and linac-IMRT treatment plans for head and neck cancer patients. Med. Dosim. 35:264–8; 2010. 5. Yang, R.; Xu, S.; Jiang, W.; et al. Dosimetric comparison of postoperative whole pelvic radiotherapy for endometrial cancer using three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and helical tomotherapy. Acta Oncol. 49:230–6; 2010. 6. Chaudhari, S.R.; Goddu, S.M.; Rangaraj, D.; et al. Dosimetric variances anticipated from breathing-induced tumor motion during tomotherapy treatment delivery. Phys. Med. Biol. 54:2541–55; 2009. 7. Kim, B.; Chen, J.; Kron, T.; et al. Motion-induced dose artifacts in helical tomotherapy. Phys. Med. Biol. 54:5707–34; 2009. 8. Kissick, M.W.; Boswell, S.A.; Jeraj, R.; et al. Confirmation, refinement, and extension of a study in intrafraction motion interplay with sliding jaw motion. Med. Phys. 32:2346–50; 2005. 9. Bortfeld, T.; Jiang, S.B.; Rietzel, E. Effects of motion on the total dose distribution. Semin. Radiat. Oncol. 14:41–51; 2004.
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10. Yang, J.N.; Mackie, T.R.; Reckwerdt, P.; et al. An investigation of tomotherapy beam delivery. Med. Phys. 24:425–36; 1997. 11. Bortfeld, T.; Jokivarsi, K.; Goitein, M.; et al. Effects of intra-fraction motion on IMRT dose delivery: statistical analysis and simulation. Phys. Med. Biol. 47:2203–20; 2002. 12. Kissick, M.W.; Mo, X.; McCall, K.C.; et al. A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management. Phys. Med. Biol. 55:2983–95; 2010. 13. Kissick, M.W.; Flynn, R.T.; Westerly, D.C.; et al. On the impact of longitudinal breathing motion randomness for tomotherapy delivery. Phys. Med. Biol. 53:4855–73; 2008. 14. Song, J.Y.; Yoon, M.S.; Nam, T.K. Respiratory organ motional effect on the dose distribution in tomotherapy. Med. Phys. 37:3238; 2010. 15. Lu, W. Real-time motion-adaptive delivery (MAD) using binary MLC: II. Rotational beam (tomotherapy) delivery. Phys. Med. Biol. 53:6513–31; 2008. 16. Lu, W. Real-time motion-adaptive delivery (MAD) using binary MLC: I. Static beam (topotherapy) delivery. Phys. Med. Biol. 53:6491–511; 2008. 17. Lu, W; Chen, M; Ruchala, KJ; et al. Real-time motion-adaptive-optimization (MAO) in TomoTherapy. Phys. Med. Biol. 54:4373–98; 2009.
Medical Dosimetry journal homepage: www.meddos.org
Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion Eunhyuk Shin, Ph.D.,n† Youngyih Han, Ph.D.,n Hee-Chul Park, M.D., Ph.D.,n Jin Sung Kim, Ph.D.,n Sung Hwan Ahn, Ph.D.,n Jung Suk Shin, M.Sc.,n Sang Gyu Ju, Ph.D.,n Doo Ho Choi, M.D., Ph.D.,n and Jaiki Lee, Ph.D.† Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and †Department of Nuclear Engineering, Hanyang University, Seoul, Korea
n
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 June 2012 Accepted 20 April 2013
This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution. & 2013 American Association of Medical Dosimetrists.
Keywords: Tomotherapy Moving tumor Intensity-Modulated Radiation Therapy 4-Dimensional radiation therapy
Introduction State-of-the-art radiation therapy, such as intensity-modulated radiation therapy (IMRT) and volumetric modulation arc therapy, has made radiation therapy significantly less prone to previously common complications,1-3 while enabling significant dose escalation by reducing critical organ dose in treatment. Helical tomotherapy is one such method of IMRT in which an x-ray source rotates around the patient, who is positioned on a couch that moves
Reprint requests to: Youngyih Han, Department of Radiation Oncology, Samsung Medical Center, #50, Irwon dong, Kang nam gu, Seoul, Korea. Tel.: +82 2 3410 2604; fax: +82 2 3410 2619; or Hee-Chul Park, Department of Radiation Oncology, Samsung Medical Center, #50, Irwon dong, Kang nam gu, Seoul, Korea. Tel.: +82 2 3410 2605; fax: +82 2 3410 2619. E-mails: [email protected], [email protected]
continuously into the gantry. A high level of intensity modulation can be achieved in this method by controlling each multileaf collimator (MLC) leaf's on-off period together with couch translation and gantry rotation speeds. It has been demonstrated that tomotherapy is more effective in regulating target conformity and normal tissue sparing compared with other conventional techniques.4,5 However, when treating a moving organ with tomotherapy, several issues remain owing to the aforementioned dynamic nature of the treatment. Previously, studies, both theoretical and experimental, have investigated the interplay of tumor motion and dynamic characteristics of treatment, such as gantry rotation period, pitch, jaw size, and MLC motion, and found that unwanted longitudinal dose modulation and symmetric and asymmetric dose blurring can occur in the treatment region for only single fraction.6-8 Unwanted dose modulation creates 2 unwanted effects: an underdose and overdose to the target region and an overdose to
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nearby normal tissues. Expanding the margin in forming the planning target volume (PTV) may compensate for underdosing in peripheral regions of a target. However, this does not fully address the dose variation (inhomogeneity) inside the target that arises from the interplay between target motion and the machine parameters. Previous studies4,9,10 have reported that dose inhomogeneity in the target varies with the relative quantities of speed of tumor vs MLC leaf motion, and the width of leaf gap vs the tumor motion amplitude. Therefore, the effects of anatomic motion and machine dynamic on treatment must be more fully understood in using tomotherapy for treating moving tumors. One widely used remedy for tumor motion in radiation therapy is the gating technique, which irradiates radiation synchronized with patient breathing. However, because of the helical nature of the treatment, this technique is not currently applicable to tomotherapy. Nonetheless, repetition of treatment for several fractions possibly lessens the underdosing or overdosing in the tumor. The cumulative effect of this practice does potentially reduce the error shown in previous studies that analyzed motion effects for one fraction on treatment.11,12 However, the effects of this practice on surrounding normal tissue are unclear and may potentially erase any compensatory effect it may have. This lack of quantitative data increases the risk associated with tomotherapy treatment for a moving organ and thus limits its applicability. This study was designed to evaluate this cumulative error in a moving target and nearby normal tissues. Specifically, the dose variation was assessed in the peripheral and central regions of the target as well as the nearby area of normal tissue for various target motions and plan parameters.
Methods and Materials Design of a moving phantom To perform dosimetry analysis in accordance with organ movement, we designed a 2-dimensional moving phantom in which motion could be programmed. The moving phantom consisted of a phantom imitation of a human thorax, a motor, and a software to control the motor. The software was designed to adjust the amplitude and period of motion in the form of a sine wave using LabVIEW 7.0 (National instrument). This program enabled us to store absolute position data of the phantom in each point of time. The positional error of the motion phantom is within 0.1 mm in 85% of the tested time, and time delay is within 0.1 second as shown in Fig. 1. The human model phantom was created by modifying an I'mRT phantom (Scanditronix-Welhoffer, Schwarzenbruck, Germany). To display the clinical target volume (CTV), acrylic material was used in making the phantom insert, as shown in Fig. 2A. The phantom insert was made of LEGO-type blocks that were 160 55 mm and 40 25 mm in size. The target shape and organ at risk (OAR) were designed to be sensitive to the craniocaudal motion. The horseshoe shape on the coronal plan was specifically selected to situate the OAR between the 2 wings, thereby affected by craniocaudal motion. Radiation treatment planning For the static-state phantom, computed tomography scans were taken using a 16-slice computed tomography scanner (LightSpeed RT16: General Electric Healthcare, Waukesha, WI). All acquired data were transferred to a tomotherapy planning software (TomoTherapy, Madison, WI), and several different plans were generated using various clinical treatment parameters, including jaw size, pitch, and modulation factor. The horseshoe-shaped CTV was on a coronal plane, and the outer dimension of the target was 9 9 cm2. An OAR was situated between the 2 wings of the horseshoe. The OAR had the shape of a rhombus on a coronal plane and a circle on a transverse plane and is shown in Fig. 2C. PTV was defined by adding a margin of 2 mm to the posterior direction and 5 mm to other directions. Treatment plan is generated with various planning parameters. The clinically preferred planning parameters such as field size 1.05 cm, pitch 0.287, and modulation factor 1.5 in tomotherapy are chosen as the standard. Additional treatment plans were prepared with changing field size 2.5, pitch 0.660, and modulation factor 2.5 as summarized in Table 1A. The 1.49 Gy per fraction was prescribed to 95% volume of the PTV to prevent film saturation in multiple exposures. The mean dose of the OAR and the maximum dose were constrained not to exceed 40% and 70% of the prescribed dose with each planning parameter, respectively.
Fig. 1. (A) Comparison of input signal to the phantom and phantom motion detected by RPM. Patient's respiration signal was used as input signal. (B) In 99.9%, 2 signals showed good agreement within 2 mm. (Color version of figure is available online.)
Tomotherapy delivery This study focused on a solid tumor in which nonrigid motion can be ignored. To investigate the motion effects for different motion parameters, measurements were taken for various periods and amplitudes. Two different motion patterns, a sine function pattern and a pattern using motion data acquired from a RPM signal of a real patient who was on respiratory training, were tested and compared with static cases as shown in Table 1B. To investigate the cumulative doses delivered over multiple fractions with respiration motion, tomotherapy plans were delivered from 1 to 5 fractions (from 1.49 Gy to 1.49 5 ¼ 6.5 Gy) in each film using GAFCHROMIC EBT-2 of the same batch number. To reduce uncertainty due to phantom position, multiple tomotherapy irradiations were performed in each experimental session without resetting the phantom. The beam delivery was started at random phase of the phantom motion to mimic real treatments. Dose distributions were measured and compared with that obtained for static phantom. Two-dimensional analyses were performed for a period of 4 seconds and amplitude of 2-cm data.
Dosimetry analysis We performed gamma index comparison between 1 fraction of irradiated film in a static phantom and computed dose distribution using the tomotherapy treatment planning system. Other comparisons using gamma index were also performed to determine interfractional change in dose distribution. The dose difference between multiexposures was found by comparing static-state dose distribution with 1-time exposure, 1- and 2-, 2- and 3-, 3- and 4-, and 4- and 5times exposure. For quantitative comparisons, each pixel value for nth multiexposure film was multiplied by (n + 1)/n for normalization and compared with (n + 1) multiexposure data. Additional dose distribution analysis was performed on the profiles intersecting the OAR center and target region. The penumbra width, minimum and maximum values of profiles, and full-width half maximum were measured. These quantities are related to dose variation in the target and OAR regions. Each test was performed 3 times to ensure our tests could be reproduced.
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evaluation of the target DAH, the underdose area (UDA) and overdose area (ODA) depicted were defined as follows: Dose area of underdose for moving Fxx Dose Area of underdose for static condition
UDA ¼
ODA ¼
Dose area of overdose for moving Fxx Dose Area of overdose for static condition
The dose area of OAR (DAO) is defined as follows: DAO ¼
Dose area of whole OAR for moving Fxx Dose Area of whole OAR for static condition
Results Dosimetry analysis
Fig. 2. Configuration of (A) a human-modeled phantom design front view of the phantom, (B) its inserted material, and (C) CTV and OAR in the experiment. (Color version of figure is available online.) Histogram-based (dose area histogram [DAH]) analysis For the target and OAR, a DAH was computed to measure CTV coverage at each multiexposure. To do this, a template for defining the target and OAR regions was applied in the process of film analysis. Every point of the target region was converted to a dose. Following this, the dose of each pixel and the total number of pixels inside the target and OAR regions were calculated. For quantitative
Table 1 Various (A) planning parameter and (B) respiration parameter used in this study (A) Plan name
Field width
Pitch
Modulation factor
Plan Plan Plan Plan
1.05 1.05 2.5 1.05
0.660 0.287 0.287 0.287
1.5 1.5 1.5 2.5
0 1 2 3
The data measured in a static phantom were in agreement with treatment planning predictions in 98.81% of the tested regions within gamma index criteria (3%/3 mm) for plan 0. The 1.19% of deviation includes setup error, machine output error, and film dosimetry uncertainty. Especially film dosimetry uncertainty was minimal. Measured data in a moving phantom exhibited large deviation, as summarized in Table 1B and Figs. 3 and 4. As shown in Figs. 3 and 4, for all tested plans, the deviation between multiexposure decreased as the treatments were further processed. As shown in Table 2A, the gamma index comparison for 1time exposure of treatment in a moving phantom and the static case failed to meet 3%/3 mm criteria in 39.05% to 28.80% of the tested area. However, from comparison of the 2-times and 1-time exposure, gamma indexes were greater than or equal to 1 in 16.34% to 9.19% of the region. In the 3-times exposure, the region over 3%/3 mm difference was almost saturation (2.57% to 9.33%). For 4-times exposure, the gamma value compared with 3-times exposure failed to meet the criteria in approximately 3% (1.14% to 3.47%) of the region. The 5-times exposure deviation was observed in less than 3% (0.69% to 2.21%) of the tested area. The total accumulated deviation is shown in Table 2B. The largest deviation was 22.14% in plan 0, followed by plan 3 (19.06%) and plan 1 (16.24%). The smallest deviation was observed in plan 2 (12.03%). Dose profiles along the cranial-caudal direction passing through the target and OAR were obtained for each multiexposure. For side-by-side comparison, each profile was multiplied by 5/n for nth times exposure. As already shown in the gamma index, the profile shape of plan 0 showed a large deviation from the static profile in the 1-time exposure of treatment. However, in the 4- and 5-times exposure, the profile shapes became very similar to each other. The observed phenomena are reproducible, as the 3 different measurements of 5 accumulated fractions exhibited the very similar profiles as shown in Fig. 5.
(B) Mode
Amplitude (cm)
Period (s)
Sine Sine Sine Sine Sine Irregular
1 4.0 2 4.0 3 4.0 2 3.0 2 5.0 Real patient respiration motion (about 2 cm, 4 s)
Fig. 3. Lateral profiles crossing OAR of treatment plan 1. (Color version of figure is available online.)
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Fig. 4. Gamma analysis for plan 0 (A) static vs 1-time exposure, (B) 1-time exposure vs 2-times exposure, (C) 2-times exposure vs 3-times exposure, (D) 3-times exposure vs 4-times exposure, and (E) 4-times exposure vs 5-times exposure. (Color version of figure is available online.)
Histogram-based Analysis
Fig. 5. Reproducibility test for treatment plan 0. (Color version of figure is available online.)
The accumulated effects of the multifractional treatment for plan 1 are presented as a DAH in Fig. 6. In Fig. 6, it can be seen that the largest dose deviation in both target and OAR was at the 1time exposure. From the 3-times exposure and on, the DAH moves closer to the static case rather than deviate further from the static curve. In Fig. 6 A and B, DAH of target and OAR at 4- and 5-times exposure is very similar to each other and eventually converge. In Table 3A, the normalized ratio of the UDA for 1-time and 2times exposure of plan 1 was 1.87 and 1.86, respectively. From the 3-times exposure, the ratio remained at 1.78. The ODA of DAH for the 1-time exposure was 1.38; however, the value was reduced to 1.22 from the 2-times exposure. In Table 3B, the UDA and ODA of the 1-time exposure are normalized to the static values and summarized for different treatment parameters. For the 4-second motion period, 3 cm of
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n (γ 4 1)
Plan 0
Plan 1
Plan 2
Plan 3
RTP and static Static and fx 1 fx 1 and fx 2 fx 2 and fx 3 fx 3 and fx 4 fx 4 and fx 5
1.19 37.71 16.34 9.33 3.47 2.21
1.81 28.80 9.19 4.71 3.26 1.93
1.69 39.05 13.45 2.57 1.14 0.69
1.99 36.76 17.13 6.77 3.42 1.91
motion was observed. However, deviation did vary between plans; plan 2, which used a larger field width than other plans, showed a smaller increment of cold region in the target compared with other plans. In addition, in a comparison of plans 1 and 3, plan 3, which had the higher modulation, showed a larger deviation. As presented in Table 3C, irregularity of the motion period slightly increased the ODA of DAH. The UDA in plan 2 did increase but was still approximately equivalent to that of regular motion for plans 1 and 3. The dose at the center of the OAR was not particularly affected by period of motion, but rather, the dose at the center of the OAR increased as motion amplitude became larger. The OAR dose increment had a positive linear relationship with the increment of penumbra size at the boundary of the target.
Plan 0
Plan 1
Plan 2
Plan 3
Discussion and Conclusions
32.33 26.77 22.50 21.14 22.14
24.4 19.24 15.02 15.46 16.24
35.26 23.64 15.21 11.68 12.03
26.29 20.76 18.66 17.06 19.06
In this study, we experimentally verified that dose distortion due to organ motion increased up to 2 to 3 times exposure, and after 3-times exposure, dose distributions in the target and OAR converged to a constant distribution. The phenomenon was verified through the gamma index test, DAH shape, DAH change, and dose at the center of the OAR (Figs. 3 and 4 and Tables 2 and 3). This is potentially owing to that the out- or in-phase deviation between the tumor motion and gantry rotation was maximally affected in the 1 to 2 fractions of treatments. Distortion levels inside the target were affected by motion parameters; larger motion amplitude and a larger motion period resulted in increased dose distortions, caused in part by extended penumbra size at the peripheral region of the target (Table 2B). In contrast, dose at the center of the OAR was affected rather by motion amplitude than motion period (Table 1B), and dose increment at the center of the OAR was caused by extended penumbra
Table 2 Percentage of area with gamma index value 41 during sine respiration mode, compared with (A) the previous fraction and (B) static isodose (amplitude 2 cm and period 4 second) RTP means planned dose distribution, and static means film measurements for static phantom (A)
(B) n (γ o 1) Static Static Static Static Static
and and and and and
fx fx fx fx fx
1 2 3 4 5
RTP (TomoTherapy Hi-Art ver. 4.2, Tomotherapy, USA); fx = repeat number of fraction.
motion amplitude caused the largest increase in UDA and ODAs, which were 2.37 and 2.48, respectively. For 2-cm amplitude of motion, the 5-second period resulted in a larger UDA/ODA of DAH compared with the 4 second or 3 second periods, which were 2.23/ 1.76, 1.87/1.38, and 1.81/1.15, respectively. DAH for regular motion and irregular motion for the 2-cm amplitude and 4-second period of motion is compared in Table 3C. No significant difference between regular and irregular
Fig. 6. DAH (dose area histogram) analysis of convergence for plan 1 (pitch 0.287, jaw width 1.05, and modulation factor 1.5) (motion amplitude 2 cm and period 4 second) (A) for target and (B) for OAR. (Color version of figure is available online.)
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Table 3 UDA (underdose area) and ODA (overdose area) and OAR area normalized static condition for (A) passing on the number of treatments in plan 0 (amplitude 2 cm and period 4 second), (B) various moving parameters, and (C) various plans and irregular motion (A)
Fx Fx Fx Fx Fx
1 2 3 4 5
UDA (target)
ODA (target)
Area (OAR)
1.87 1.86 1.78 1.78 1.78
1.38 1.22 1.22 1.21 1.23
1.40 1.33 1.33 1.26 1.25
(B)
4s 4s 4s 5s 3s
2 cm 1 cm 3 cm 2 cm 2 cm
UDA (target)
ODA (target)
Area (OAR)
1.87 1.08 2.37 2.23 1.81
1.38 1.03 2.48 1.76 1.15
1.40 0.96 1.49 1.21 1.20
(C) UDA (target)
ODA (target)
Area (OAR)
Plan 0
Regular Irregular
2.01 2.02
1.75 1.76
1.34 1.35
Plan 1
Regular Irregular
1.55 1.55
1.42 1.46
1.31 1.28
Plan 2
Regular Irregular
1.42 1.46
1.58 1.60
1.20 1.21
Plan 3
Regular Irregular
2.59 2.58
1.49 1.52
1.31 1.29
size owing to motion amplitude. Analysis of DAH changes in Table 3 suggests irregularity of motion not to be a significant factor in dose distortion compared with other motion parameters and plan complexity. Regarding plan complexity, the more complicated plan with the larger modulation factor (2.5: plan 3) resulted in larger dose deviation than the plan with a modulation factor of 1.5 (plan 1) over the static case (Table 3C, plan 3 vs plan 1). The observed phenomenon is thought to be reproducible because 3 different measurements of an accumulated 5 fractions of treatments showed very similar trends (Fig. 5). Bortfield et al.11 used statistical analysis to investigate dose distributions in a moving organ treated with IMRT with linear accelerators and concluded that dose distribution after several fractions was close to the Gaussian around the expected value. In addition, with 5-mm amplitude of organ motion for 30 fractions of treatments, the standard deviation was within 1% of the expected value. Although this current study investigated tomotherapy for a moving organ, the convergence of dose distribution after 2 to 3 fractions is thought to be in agreement with their findings, and several similarities can be found. As in the Bortfield study, we found a large dose difference for the initial 2 to 3 fractions. However, in our study, the deviation appears to be significantly larger. This is potentially owing to the smaller target volume and closely situated OAR position to the target. Using simulation studies, Kissick et al.13 investigated the effect of irregularity of a patient's breathing on the dose distribution along the cranial-caudal direction. They reported that the random breathing amplitude relative to jaw size has a linear relation to
dose error probability. While for regular breathing motion, when random error effects were not expected, and if the peak-to-peak amplitude of the target motion is smaller than the jaw size, the unwanted dosimetric error was negligible. However, we did not observe the same effect, potentially owing to the difference in target geometry, which was very narrow, compared with jaw size in the cranial-caudal direction. In our study, all regular breathing motions caused dose distribution errors, even when the motion amplitude was smaller than jaw size. Compared with the theoretical study by Kim et al.,7 which reported 3 different types of motion-induced artifacts, dose rounding effects were more clearly observed in our experiments. Dose riffling artifacts caused by dose redundant in tomotherapy were larger for longer periods of target motion. Regarding machine parameters, the largest jaw size (plan 2) minimized the deviation. For the same jaw size, a smaller modulation factor plan showed less deviation (plan 1 vs plan 3). For the same jaw width and modulation factor, a smaller pitch showed less dose distortion (plan 2 vs plan 1) (Table 2). Our findings are in agreement with those of previous studies by Chaudhari and Goddu2 and Song et al.,14 which reported that larger jaw width relative to the motion amplitude and low couch speed (smaller pitch) reduced the motion-induced error. To overcome motion-induced artifacts, several suggestions have been proposed in recent years. One such strategy has been motion-adaptive beam delivery on static and dynamic15,16 gantry motions. This method rearranges the projections and leaf indexes of preprogrammed leaf sequences (sinogram) according to instantaneous target position, if the target position can be detected accurately. However, although the method is promising, accurate detection of tumor position is still a challenging issue.17 A realistic method in current stage of tomotherapy is to manage motion amplitude to be small compared with jaw size. For regular breathing motions without drifting effects, dose deviation was predicted to be minimal with acceptably small dose blurring. However, as our results indicate, this strategy is still limited to tumors that are comparably larger in dimension, compared with jaw width. When the tumor size is small, this general rule does not apply. According to our study results, practical use of moving target treatment with tomotherapy requires taking dose-blurring effects into consideration in determining the PTV and requires the selection of a larger jaw size with a low modulation factor. Also, a training program for patients to breathe in small amplitude, short period, and, if possible, regular pattern would be beneficial. In summary, tomotherapy on a moving target causes a large dose deviation in the first exposure; however, within 3 fractions, the deviation converges to some constant value depending on level of plan difficulty. Pretreatment measurements for 3 fractions of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.
Acknowledgments This research was supported by IN-SUNG Foundation for Medical Research and the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science, and Technology (2010-0011771). References 1. Jiang, S.B.; Pope, C.; Al Jarrah, K.M.; et al. An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments. Phys. Med. Biol. 48:1773–84; 2003. 2. Chaudhari, S.; Goddu, S. Breathing motion‐induced dose delivery error evaluations as applied to tomotherapy dose delivery. Med. Phys. 34:2561; 2007.
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