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. 2022 Dec 1;17(12):e0278422. doi: 10.1371/journal.pone.0278422

Comparison of dosimetric effects of MLC positional errors on VMAT and IMRT plans for SBRT radiotherapy in non-small cell lung cancer

Jia Deng 1,2,*, Yun Huang 3, Xiangyang Wu 1, Ye Hong 4, Yaolin Zhao 2
Editor: Devarati Mitra5
PMCID: PMC9714892  PMID: 36454884

Abstract

The positional accuracy of multi-leaf collimators (MLC) is important in stereotactic body radiotherapy (SBRT). The aim of this study was to investigate the impact between MLC positional error and dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC). Fifteen patients with NSCLC were selected to design the 360 SBRT-VMAT plans and the 360 SBRT-IMRT error plans. The DICOM files for these treatment plans were imported into a proprietary computer program that introduced delivery errors. Random and systematic MLC position (0.1, 0.2, 0.5, 1.0, 1.5, and 2.0 mm) errors were introduced. The systematic errors were shift errors (caused by gravity), opening errors, and closing errors. The CI, GI, d2cm and generalized equivalent uniform dose (gEUD) were calculated for the original plan and all treatment plans, accounting for the errors. Dose sensitivity was calculated using linear regression for MLC position errors. The random MLC errors were relatively insignificant. MLC shift, opening, and closing errors had a significant effect on the dose distribution of the SBRT plan. VMAT was more significant than IMRT. To ensure that the gEUD variation of PTV is controlled within 2%, the shift error, opening error, and closing error of IMRT should be less than 2.4 mm, 1.15 mm, and 0.97 mm, respectively. For VMAT, the shift error, opening error, and closing error should be less than 0.95 mm, 0.32 mm, and 0.38 mm, respectively. The dose sensitivity results obtained in this study can be used as a guide for patient-based quality assurance efforts. The position error of the MLC system had a significant impact on the gEUD of the SBRT technology. The MLC systematic error has a greater dosimetric impact on the VMAT plan than on the IMRT plan for SBRT, which should be carefully monitored.

Introduction

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and is associated with increased morbidity and mortality [13]. Stereotactic body radiotherapy (SBRT) has become the standard treatment for patients with medically inoperable early-stage NSCLC. Compared with conventionally fractionated radiotherapy, SBRT allows larger doses to be delivered in a small number of fractions, resulting in a higher biologically effective dose [4]. To limit and minimize radiation-induced damage to normal tissue, SRBT requires the concentration of high doses to the planned target volume (PTV) and a large dose fall-off outside the PTV. Linac-based SBRT can be mainly performed with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). Modulated dose distribution in IMRT plans can be achieved with a multi-leaf collimator (MLC), in which the leaves are in motion during irradiation. VMAT delivers a dose with precise synchronization of the gantry rotation speed, MLC motion, and dose rate [57]. Previous studies have found that the conformity and uncertainty of SBRT dose delivery are more dependent on the position of the MLC leaf than conventionally fractionated radiotherapy, which could lead to more serious complications [810]. Therefore, it is necessary to investigate the dosimetric effects of MLC leaf position errors in both IMRT and VMAT for SBRT. The aim of this study was to investigate the effects of systematic and random MLC leaf position errors on lung SBRT with IMRT/VMAT in patients with NSCLC. We investigated the differences in dose sensitivity between IMRT and VMAT for four types of MLC errors and sought to determine their benefits and limitations.

Methods and materials

Patient selection

Fifteen patients clinically diagnosed with stage I–II central lung cancer were selected for this study. They were ten men and five women, aged between 45 and 76 years, with a planned target volume between 3.6 and 13.4 cm3. Ten patients had squamous cell carcinoma and five had adenocarcinoma. The prescribed dose for lung SBRT was 50 Gy to the PTV, and the limited dose of OARs was considered according to RTOG protocols. All data were obtained after the ethics committee (Medical ethics committee of Shaanxi Provincial Cancer Hospital) approval, informed consent waiver, and verbal informed consent for the study was obtained.

Treatment planning

Two types of SBRT plans, IMRT and VMAT, were prepared for each of the fifteen patients. For the VMAT plans, one arc was used with a gantry range of 179° to 181° with the collimator set to 10°, and the other was delivered with a collimator angle of -10° and a gantry rotation between 181° and 179°. Seven fields were set up in the IMRT plans. The gantry angles of the fields were 0°, 52°, 104°, 156°, 208°, 260°, and 312° with a collimator angle of 10°. Under the same dose optimization conditions, the IMRT and VMAT plans were used for each case.

The plans were created using Eclipse TPS version 13.5 with a photon optimizer for Photon Optimizer (PO) and an Anisotropic Analytical Algorithm (AAA) for dose distribution with a dose calculation grid of 1.0 mm. All plans were reproduced on a TrueBeam (Varian)equipped with 60 pairs of leaves, which had 40 inner- and 20 outer-leaf pairs with a width of 0.5 and 1 cm, respectively.

Simulation of MLC leaf position errors

Three types of systematic and one type of random MLC position errors were introduced into the original VMAT and IMRT plans of NSCLC for error magnitudes of 0.1, 0.2, 0.5, 1, 1.5, and 2 mm. Fig 1, shows a graph illustrating the different types of MLC position errors in this study. Type 1 errors were shift errors in which both MLC banks moved to the left or the right by adding the same error magnitude to each leaf position, while the subfield magnitude remained unchanged. when the gantry is from -179 to 0 degrees, the MLC bank shift to the left, as shown in Fig 1(B), and when the gantry from 0 to 179 degrees, the MLC bank shift to the right, as shown in Fig 1(C) [11]. Considering the influence of gravity on the MLC positions, the direction of the shift error was defined as a function of the gantry angle. Type 2 and type 3 errors were opening and closing errors, and both MLC banks moved in opposite directions with the same error magnitude, increasing and decreasing the MLC leaf gap, respectively. Type 4 errors were simulated random errors that were introduced by adding or subtracting random errors determined by sampling a Gaussian function centered on zero, with a standard deviation equal to the error magnitude. To avoid potential errors and unintentional duplication, we generate a new Gaussian random distribution for each error plan, so that the same errors are not added to different exposure fields and plans.

Fig 1. MLC position errors are introduced to each SBRT plan.

Fig 1

(a) baseline plan; (b)(c) Type1, shift error; (d)Type2, opening error; (e)Type3, closing error; (f)Type4, random error.

Plans without introduced errors were referred to as “Baseline” plans. First, the fifteen “Baseline” treatment plans were exported from the TPS and then imported into an in-house program written in MATLAB. The in-house program was used to modify the MLC leaf positions with simulated errors. Then, all error-related treatment plans were imported into the TPS for dose recalculation. If an error resulted in a negative leaf gap, the MLC positions for the gap were re-adjusted to zero.

Plan evaluation

To evaluate dosimetric differences between the simulated plans and the “baseline” plans, routine plan evaluation methods were used, including isodose distributions and DVH. All plans were evaluated by conformity index(CI), gradient index(GI), D2cm, and generalized Equivalent Uniform Dose (gEUD). The CI reflected the conformity of the shape and size of the isodose envelope to the PTV, the CI represented the conformity of a reference isodose to the PTV, defined as:

CI=V(P,R)VP×V(P,R)VR (1)

where V(P,R) is the PTV volume covered by the prescribed isodose surface, VR is the volume covered by the prescribed isodose surface, and VP is the PTV volume. The GI was defined as the degree of dose drop-off outside the PTV. GI was calculated using the following equation:

GI=R50%R100% (2)

where R50% is the ratio of the 50% prescription isodose volume to the PTV and R100% is the ratio of the 100% prescription isodose volume to the PTV.

D2cm represents the ratio of the maximum dose to the prescribed dose 2 cm from the PTV in any direction.

gEUD was used to summarize the total DVH in a single metric, defined as the dose that would have the same biological effect if delivered uniformly to the entire volume. gEUD can be expressed as follows [12,13]:

gEUD=(imviDia/imvi)1a (3)

where m is the number of voxels in the volume of interest and Di and vi are the dose and volume in the i-th voxel, respectively. a is the tumor-or normal tissue-specific parameter describing the dose–volume effect, which can be obtained from clinical outcome data. According to the research results, the value of a was set to -20 for PTV, 20 for spinal cord, and 1 for both the lungs and heart [14]. In addition, the plans were analyzed to identify the relative percentage change in gEUD for each error magnitude, expressed by ΔgEUDError:

gEUDError=gEUDErrorgEUDBaselinegEUDBaseline×100% (4)

where the subscript “Error” indicates the plan being evaluated.

Results

Statistical analysis

All statistical analyses were performed with SPSS 20.0, and a paired t-test was used to compare the two groups. Experimental data are expressed as mean ± standard deviation, and P<0.05 was considered statistically significant in this study.

DVH comparison between IMRT and VMAT

Fig 2 shows A sample dose–volume histogram (DVH) of the PTV, left lung, lung, heart, and spinal cord for the baseline plan and different simulation plans with an MLC position error of 2 mm for each case. It can be seen from the diagram that systematic MLC opening and closing errors can cause noticeable dosimetric changes in the PTV and OARs. In addition, IMRT plans are less sensitive than VMAT plans to dose deviations caused by the same type of MLC error.

Fig 2. A sample dose–volume histogram of patient 5.

Fig 2

This figure shows A sample DVH of the PTV, left lung, lung, heart, and spinal cord for the baseline plan and different simulation plans with an MLC position error of 2 mm for each case. 2(a) IMRT plans; 2(b) VMAT plans.

Dosimetric parameters comparison of PTV between IMRT and VMAT

The results of the percentage changes for CI, GI, and D2cm are shown in Fig 3 for all four types of MLC position errors. Fig 3(A) shows that the CI decreased with increasing MLC error. The changes in the closing error were the largest, followed by the opening error, and the random error was minimal. In addition, IMRT plans are less sensitive than VMAT plans to dose deviations caused by the same type of MLC error.

Fig 3. The percentage changes for CI, GI, and D2cm for all types of MLC position errors in IMRT plans and VMAT plans.

Fig 3

3(a) CI decreased with increasing MLC error; 3(b) the relative percentage change of GI compared to each type of MLC error; 3(c) the relative percentage change of D2cm compared to each type of MLC error.

Fig 3(B) shows the relative percentage change of GI compared to each type of MLC error. It can be seen that the random error had no obvious effect on the GI of IMRT and VMAT plans. The largest change in CI was observed when opening the MLC leaves, which showed a rapid dose fall-off.

As shown in Fig 3(C), D2cm is positively correlated with the opening and shifting errors and decreases with the increase of the closing error. For the type of the same error, the D2cm values for the IMRT plans were slightly lower than those for the VMAT plans.

Fig 4 shows the gEUD variation in the PTV caused by MLC errors. As shown in Fig 4, IMRT plans are less sensitive than VMAT plans to dose deviations caused by the same type of MLC errors. Systematic errors have a greater impact on the PTV gEUD variation than random errors. For an errors up to 2 mm, the changes in PTV gEUD of IMRT and VMAT plans caused by opening errors were 3.27% and 8.11%, respectively, caused by closing errors of -4.17% and -8.14%, respectively, which were caused by a shift error of -1.66% and—4.38% respectively. The influence of the random error is negligible.

Fig 4. The gEUD variation in the PTV caused by MLC errors.

Fig 4

4(a) The gEUD variation in IMRT plans. 4(b) The gEUD variation in VMAT plans.

Dosimetric parameters comparison of OAR between IMRT and VMAT

Tables 14 summarize the gEUD variation in the OAR of the IMRT and VMAT plans. For the OARs, the random error had a negligible effect on the gEUD. In contrast, the opening and closing errors cause a large change in the gEUD. The biological dose changes caused by shift errors had a significant effect on the whole lung for the IMRT plans and on the heart for the VMAT plans. The biological dose changes for the OARs VMAT plans were significantly higher than those for the IMRT plans when opening or closing the MLC leaves.

Table 1. The gEUD variation in the OAR of the IMRT and VMAT plan for shift error.

Error Plan type Cord (%) Heart (%) Lung (%) Left Lung (%)
0.1mm IMRT 0.114±0.409 -0.06±0.132 -0.083±0.040 -0.07±0.041
VMAT -0.018±0.101 -0.074±0.098 -0.005±0.039 0.003±0.044
P 0.031 0.162 <0.01 <0.01
0.2mm IMRT 0.219±0.809 -0.137±0.27 -0.166±0.08 -0.151±0.079
VMAT -0.036±0.199 -0.146±0.196 -0.007±0.077 0.004±0.088
P 0.031 0.163 <0.01 <0.01
0.5mm IMRT 0.483±1.935 -0.306±0.649 -0.428±0.194 -0.384±0.193
VMAT -0.087±0.487 -0.359±0.492 -0.017±0.194 -0.016±0.188
P 0.029 0.163 <0.01 <0.01
1.0mm IMRT 0.836±3.803 -0.661±1.279 -0.911±0.383 -0.801±0.386
VMAT -0.154±0.936 -0.707±0.982 -0.041±0.388 0.002±0.444
P 0.028 0.165 <0.01 <0.01
1.5mm IMRT 1.113±5.686 -1.072±1.892 -1.45±0.575 -1.275±0.587
VMAT -0.201±1.342 -1.057±1.456 -0.081±0.581 -0.02±0.673
P 0.026 0.169 <0.01 <0.01
2.0mm IMRT 1.268±7.528 -1.58±2.428 -2.066±0.776 -1.664±0.985
VMAT -0.215±1.697 -1.39±1.938 -0.137±0.774 -0.06±0.908
P 0.025 0.175 <0.01 <0.01

Table 4. The gEUD variation in the OAR of the IMRT and VMAT plan for random error.

Error Plan type Cord (%) Heart (%) Lung (%) Left Lung (%)
0.1mm IMRT -0.01±0.113 -0.003±0.05 0.005±0.045 0.006±0.048
VMAT 0.049±0.101 0.048±0.135 0.063±0.12 0.067±0.113
P 0.032 0.176 <0.01 <0.01
0.2mm IMRT 2.113±6.965 -0.058±0.15 -0.07±0.115 -0.068±0.118
VMAT 0.07±0.233 -0.088±0.329 -0.076±0.212 -0.027±0.249
P 0.033 0.162 <0.01 <0.01
0.5mm IMRT -0.007±0.486 -0.104±0.362 -0.085±0.24 -0.078±0.229
VMAT -0.021±0.951 0.28±0.785 0.332±0.643 0.201±0.763
P 0.032 0.168 <0.01 <0.01
1.0mm IMRT -0.248±1.089 -0.31±0.521 -0.352±0.592 -0.352±0.572
VMAT -0.039±0.898 -0.056±1.33 -0.046±0.975 -0.044±0.901
P 0.034 0.174 <0.01 <0.01
1.5mm IMRT 0.028±1.367 -0.464±0.929 -0.145±0.905 -0.119±0.926
VMAT 0.323±2.257 0.212±1.945 0.217±1.69 0.065±1.566
P 0.031 0.166 <0.01 <0.01
2.0mm IMRT -1.662±2.568 -1.218±1.43 -1.185±1.393 -1.173±1.436
VMAT 0.927±3.598 1.326±4.052 1.84±3.334 1.39±3.399
P 0.042 0.211 <0.01 <0.01

Table 2. The gEUD variation in the OAR of the IMRT and VMAT plan for opening error.

Error Plan type Cord (%) Heart (%) Lung (%) Left Lung (%)
0.1mm IMRT 0.307±0.233 0.491±0.065 0.408±0.053 0.404±0.055
VMAT 0.645±0.153 0.774±0.151 0.742±0.157 0.753±0.16
P 0.033 0.169 <0.01 <0.01
0.2mm IMRT 0.627±0.49 0.985±0.132 0.818±0.107 0.81±0.11
VMAT 1.301±0.323 1.553±0.297 1.545±0.272 1.507±0.32
P 0.074 0.176 <0.01 <0.01
0.5mm IMRT 1.518±1.133 2.471±0.333 2.047±0.267 2.029±0.276
VMAT 3.227±0.765 3.877±0.751 3.712±0.784 3.769±0.801
P 0.037 0.197 <0.01 <0.01
1.0mm IMRT 3.098±2.412 4.943±0.669 4.094±0.535 4.057±0.552
VMAT 6.466±1.533 7.771±1.499 7.428±1.572 7.542±1.607
P 0.043 0.241 <0.01 <0.01
1.5mm IMRT 4.618±3.595 7.418±1.011 6.139±0.804 6.083±0.829
VMAT 9.718±2.31 11.667±2.258 11.152±2.365 11.32±2.419
P 0.051 0.294 <0.01 <0.01
2.0mm IMRT 6.140±4.809 9.891±1.351 8.182±1.072 8.108±1.106
VMAT 12.985±3.101 15.574±3.021 14.879±3.163 15.102±3.235
P 0.06 0.358 <0.01 <0.01

Table 3. The gEUD variation in the OAR of the IMRT and VMAT plan for closing error.

Error Plan type Cord (%) Heart (%) Lung (%) Left Lung (%)
0.1mm IMRT -0.351±0.287 -0.49±0.066 -0.414±0.054 -0.41±0.055
VMAT -0.414±0.159 -0.423±0.214 -0.444±0.124 -0.464±0.129
P 0.032 0.162 <0.01 <0.01
0.2mm IMRT -0.7±0.572 -0.974±0.13 -0.824±0.107 -0.817±0.109
VMAT -1.248±0.247 -1.449±0.21 -1.391±0.237 -1.4±0.24
P 0.031 0.152 <0.01 <0.01
0.5mm IMRT -1.774±1.43 -2.428±0.32 -2.053±0.271 -2.039±0.27
VMAT -2.692±0.548 -3.153±0.51 -3.037±0.541 -3.071±0.551
P 0.031 0.145 <0.01 <0.01
1.0mm IMRT -3.538±2.809 -4.846±0.636 -4.104±0.534 -4.072±0.537
VMAT -6.092±1.105 -7.025±0.942 -6.769±1.076 -6.794±1.082
P 0.027 0.118 <0.01 <0.01
1.5mm IMRT -5.236±4.087 -7.26±0.946 -6.155±0.795 -6.106±0.804
VMAT -8.679±1.524 -10.037±1.351 -9.667±1.513 -9.712±1.527
P 0.026 0.108 <0.01 <0.01
2.0mm IMRT -6.955±5.341 -9.664±1.251 -8.204±1.054 -8.138±1.067
VMAT -11.93±1.975 -11.902±4.772 -13.211±1.948 -13.23±1.951
P 0.024 0.1 <0.01 <0.01

Comparison of dose sensitivity between IMRT and VMAT

Table 5 lists the dose sensitivity values of gEUD for the PTV and the OARs for the four types of MLC errors. The results showed that among the four types of MLC errors, the opening and closing dose sensitivities were the highest. The IMRT plans are seen to exhibit lower sensitivity than VMAT plans. For opening errors, the percentage changes in gEUD of PTV for IMRT and VMAT plans were -2.0623 and-5.3143%/mm, respectively. The dosimetric effects of closing errors are opposite to those of opening errors, and the gEUD sensitivity for the PTV was found to be 1.737 and 6.222%/mm for IMRT and VMAT plans, respectively. The shift error had a small effect on the gEUD, and the gEUD sensitivity values of PTV for IMRT and VMAT plans were -0.819 and -2.136%/mm, respectively. Random errors changed the gEUD insignificantly within 2 mm. For IMRT plans, a gEUD deviation in the PTV of less than 2% ensures that the deviations in shift, opening, and closing errors are less than 2.4, 1.15, and 0.97 mm, respectively. For VMAT plans, to keep the gEUD deviation in the PTV within 2%, it is necessary to ensure that the deviations in the shift, opening, and closing errors are less than 0.95, 0.32, and 0.38 mm, respectively.

Table 5. Dose sensitivity analysis of MLC error to PTV and OAR in IMRT and VMAT plans.

Type1 Type2 Type3 Type4
Dose sensitivity (%/mm) R 2 Dose sensitivity (%/mm) R 2 Dose sensitivity (%/mm) R 2 Dose sensitivity (%/mm) R 2
PTV IMRT -0.819 0.957 1.737 0.999 -2.062 0.999 -0.197 0.532
VMAT -2.136 0.961 6.222 0.999 -5.314 0.990 -0.023 0.001
Cord IMRT 2.568 0.775 3.286 0.999 -3.718 0.999 -0.616 0.498
VMAT 0.037 0.995 6.557 0.999 -5.986 0.999 0.477 0.571
Heart IMRT -0.679 0.989 5.044 0.999 -4.920 0.999 -0.521 0.928
VMAT -0.697 0.999 7.786 0.999 -6.236 0.990 0.491 0.580
Lung IMRT -1.079 0.996 4.192 0.999 -4.200 0.999 -0.477 0.701
VMAT -0.065 0.954 7.456 0.999 -6.615 0.999 0.665 0.563
Left Lung IMRT -0.848 0.999 4.055 0.999 -4.068 0.999 -0.446 0.658
VMAT -0.025 0.699 7.550 0.999 -6.625 0.999 0.476 0.503

Discussion

The accuracy of the MLC position is a critical factor for the quality of treatment in clinical inverse intensity-modulated radiotherapy. Especially in fractionally high-dose radiotherapy, referred to as SBRT, the MLC leaf position error leads to a change in the planned dose distribution. Therefore, the accuracy of the MLC position can be ensured during the treatment process, to take advantage of the planned intensity-modulated radiotherapy.

The accuracy of MLC leaf positioning is highly dependent on leaf position repeatability precision, calibration, motor age, and gravity effects, among other factors [15]. A deviation in the MLC leaf position directly results in a deviation in target and OAR dose [9]. ICRU 142 suggested an action level of 1 mm gap width deviation [16]. Chow et al. examined the VAMT plan for SBRT using log files, and found that the maximum MLC positional error was 0.6 mm [17]. Oliver et al. analyzed the effect of MLC positioning errors for VMAT plans and concluded that the MLC positioning errors for VMAT treatments should be within 0.6 mm to keep the dose variation in the target coverage within 2% [18]. In addition, they reported that the dose sensitivity for systematic MLC gap opening and closing errors in RapidArc plans for prostate cancer was 8.2 and -7.2% per mm, respectively [9]. Ai et al. reported a significant difference in dose sensitivity between MU-weighted and unweighted MLC position errors in SBRT radiotherapy [8]. Thus, MLC errors have a significant impact on the effectiveness of plan execution.

In this study, we evaluated the potential clinical impact of simulated MLC position errors on IMRT/VMAT plans by calculating the gEUD variation in NSCLC SBRT and investigated the difference in dose sensitivity between IMRT and VMAT in the presence of systematic MLC errors and random errors. The results showed that MLC positional errors affected target coverage, OAR protection, CI, and HI of IMRT and VMAT plans [19]. In addition, The IMRT plans are seen to exhibit lower sensitivity than VMAT plans. This was possibly due to the MLC positional errors which depended on gap statistics and jaw sizes. In addition, VMAT requires MLC leaves, gantry positions, and dose rates to change dynamically during irradiation [20,21].

The gEUD was based on both the physical dose information and the radiobiological response of the tumor, whereas the positional accuracy of the MLC leaves can directly cause both radiation volume and dose deviations. Therefore, gEUD was used in this study to evaluate the effects of MLC positional errors on IMRT/VMAT plans [18]. Our data showed that for shift errors, the gEUD sensitivity values of PTV for IMRT and VMAT plans were -0.819 and -2.136%/mm, respectively. The effects are symmetrical with respect to the signs of the systematic errors. It can be seen from Table 5 that the dosimetric effects of systematic errors are strongly linearly correlated with the magnitude of the error. Similar results have been reported previously [9]. The results for systematic opening and closing MLC errors in this study estimated a gEUD sensitivity of -2.0623 and 1.737%/mm for IMRT and -5.3143 and 6.222%/mm for VMAT, which is not consistent with the study by Oliver et al [9]. The explanation for this is, that in SBRT, the target volume is smaller than in conventional irradiation plans; therefore, the subfields formed by the MLC are smaller. The smaller the subfields, the greater the dosimetric impact of opening or closing errors on the treatment plans [18,19]. Fig 5 summarizes the number of control points and the size of the apertures at each control point formed by opposing pairs of MLC leaves during dynamic transmission of the IMRT/VMAT plans. Based on the results shown in Fig 5, it is apparent that IMRT plans require about 13000 different leave pair combinations, of which 21% are separated by less than 2 cm. In contrast, VMAT plans require about 16500 leave pair combinations, of which 64% are separated by less than 2 cm. Further analysis indicated that VMAT tends to use more small-area subfields than IMRT. In particular, VMAT consists of a large number of subfields with stenosis strips, that are much larger than those of IMRT. This is associated with a larger fractional change in relative output factor(ROF) because the ROF is steeper for smaller subfields [18,19]. The mean values for VMAT and IMRT were 2926.31±334.42 and 1971.23±216.45, respectively. Similar to previous studies, dose sensitivity increased with the increasing value of MU [8].

Fig 5. Frequency histogram of all windows formed by MLC leaf pairs during dynamic window delivery of all IMRT and VMAT plans.

Fig 5

In conclusion, the shift, opening, and closing errors of the MLC leaves had a significant effect on the dose distribution of the SBRT plans, and the effects on VMAT were more pronounced than those of IMRT. The random error had less influence and could be ignored. If a 2% change in gEUD of the PTV was assumed to be an acceptable level of dose deviation due to MLC effects alone, then shift, opening, and closing errors in leaf position for IMRT would have to be limited to 2.4, 0.97, and 1.15 mm, respectively, and for VMAT, they would have to be limited to 0.95, 0.32, and 0.38 mm, respectively [9,22].

The dose sensitivity results obtained in this study can be used to guide clinical quality assurance measures. Systematic MLC errors had a significant impact on the gEUD of SBRT. In particular, VMAT plans have a greater impact on dose distribution than IMRT plans and should be carefully monitored. In this study, we simulated that the MLC errors may be within a certain range and their dosimetric impact on SBRT plans.

Conclusion

In this study, we investigated the effects of intentional application of MLC position errors on NSCLC SBRT IMRT/VMAT treatment plans. We found that systematic errors had the greatest impact on CI, GI, D2cm, and gEUD for all parameters assessed. For VMAT plans, there was a large variability in the MLC errors. Based on the dosimetric results, this study provides a guide for the development of performance standards for multi-leaf collimators.

Acknowledgments

We would like to thank Xiaobin Chang, Kun Zhang, and Qiang Zhao for their support during the manuscript preparation.

Data Availability

All minimal dataset files are available from the figshare database (accession number(s) https://doi.org/10.6084/m9.figshare.21366744.v1).

Funding Statement

JD was supported by grants from the Health research Program of Shaanxi Provincial Health Commission (No. 2022D037). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Devarati Mitra

13 Sep 2022

PONE-D-22-19213Comparison of Dosimetric Effects of MLC Positional Errors on VMAT and IMRT plans for SBRT Radiotherapy in Non-small Cell Lung CancerPLOS ONE

Dear Dr. Deng,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================This study provides further support for an existing body of knowledge. With the changes suggested by the reviewer the manuscript would be significantly strengthened and likely worth publishing.==============================

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We look forward to receiving your revised manuscript.

Kind regards,

Devarati Mitra

Academic Editor

PLOS ONE

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Additional Editor Comments:

This study helps provide further support for an existing body of knowledge. As noted by the reviewer while not the most novel concept it is well written and does provide further foundation for current practice. With the changes suggest the study would be much stronger and likely worth publishing.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This work is clear and concise with few grammatical errors.

This work is not novel, as other approaches have inserted random and systematic errors into plans to quantify impact on dosimetry. Rather, it reinforces continuing work that monitors performance capabilities of Varian Truebeam MLCs.

General recommendations:

To bring simulated results of this work more into context, I suggest that the authors examine the frequency and magnitude of their own truebeam MLC errors. This would show if experimental results here would actually be of use clinically or for QA purposes. If authors are unable to do so, please consider the citations that are currently in the work about frequency and magnitude of MLC error (Chow et al). When authors recommend that errors must be less than a certain amount in lines 173, this assumes that a systematic shift to all MLCs must exist. Please indicate based on citations or your own clinical values if this situation could occur and/or how it would be controlled or monitored.

Tables in this work do not contain consistent significant digits or units of dose. Please address.

Do clinicians or physicists at your clinic use gEUD to make clinical decisions? How is gEUD a useful metric to monitor for QA? Please address.

Please indicate how random errors were simulated? No information is provided. What distribution was used to create random errors? Please cite the following paper in your discussion, as it also simulates random and systematic errors and investigates dosimetric impact: https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.12677

Specific comments:

Abstract:

“The aim of this study was to investigate the difference between MLC positional error and dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC).”

The usage of the word “difference” is incorrect here and meaning is not correct.

Instead: The aim of this study was to investigate the impact of MLC positional error on dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC)

Lines 225

That all leaves would be systematically shifted by these amounts is very unlikely. The Varian Truebeam monitors leaf positions many times over per second and prevents a beam on if leaves are out of tolerance.

Line 227-228

“In particular, VMAT plans have a greater impact on dose distribution than IMRT plans and should be carefully monitored”.

Authors should be more specific. The MLC positions are already closely monitored and recorded in the dynalog files. Please indicate what is meant. How specifically do reviewers plan to use these results to guide clinical QA measures? Do the authors mean IMRTQA? Is this work part of a commissioning process, determination of baseline, or educational in nature?

I am of the opinion that this study is very useful for teaching of medical physicists and demonstrating how different MLC errors can impact a patients treatment (if these errors were to not be caught by MLC control system).

Line 230

“In this study, we simulated that the MLC errors may be within a certain range.”

This sentence is not correct. Instead it should read that “in this study, we simulated MLC errors within a certain range and their dosimetric impact on SBRT plans.”

Line 231

“In future research, it would be useful to conduct experimental studies to determine the typical long term accuracy and precision of the relevant parameters for SBRT delivery”

What relevant parameters do the authors mean? This sentence is not specific. Authors need to please recognize that relevant measures that quantify dosimetric impact of MLC errors is a well-studied sub field of medical physics, so what is the authors motivation for continued monitoring?

**********

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Reviewer #1: No

**********

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PLoS One. 2022 Dec 1;17(12):e0278422. doi: 10.1371/journal.pone.0278422.r002

Author response to Decision Letter 0


20 Oct 2022

Dear Editors:

Many thanks for your letter and the reviewers’ comments concerning our manuscript entitled “Comparison of Dosimetric Effects of MLC Positional Errors on VMAT and IMRT plans for SBRT Radiotherapy in Non-small Cell Lung Cancer”. These comments are all valuable and very helpful for revising and improving the manuscript. We have revised the manuscript according to your kind advices and the reviewer’s suggestions. The main revisions and responses to the reviewer’s comments are as follows:

Editor:

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Reply: Thank you for your suggestion. We have modified it according to the requirements.

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Reply: Thank you for your suggestion. We have included an ethics statement in the methods section, as detailed in lines 53-55 of the manuscript. Oral informed consent was obtained by telephone and the transcript has been uploaded in the ethics statement.

3. Please note that PLOS ONE has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, all author-generated code must be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse. New software must comply with the Open Source Definition

Reply: Thank you for your suggestion. It was requested that the code be shared. And it can be accessed through the following DOI path: https://doi.org/10.6084/m9.figshare.21342072

4. Thank you for stating in your Funding Statement:

"JD was supported by grants from the Health research Program of Shaanxi Provincial Health Commission (No. 2022D037)."

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

Reply: Thank you for your suggestion. The requested changes were made, and the revised fund statement was incorporated into the cover letter. The content is as follows: “This work was supported by grants from the Health Research Program of Shaanxi Provincial Health Commission (No. 2022D037). There was no additional external funding received for this study.”

5. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

Reply: Thank you for your suggestion.

We have shared our raw data and the minimal dataset at:

https://doi.org/10.6084/m9.figshare.21366744.v1

Our institute's ethics committee can be reached at the following address:

Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China

Tel:+86-029-85276017

6. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

Reply: Thank you for your suggestion. The full ethical statement is included in the methods section, on lines 53-55 of the article.

Reviewer # 1

1. General recommendations:

To bring simulated results of this work more into context, I suggest that the authors examine the frequency and magnitude of their own truebeam MLC errors. This would show if experimental results here would actually be of use clinically or for QA purposes. If authors are unable to do so, please consider the citations that are currently in the work about frequency and magnitude of MLC error (Chow et al). When authors recommend that errors must be less than a certain amount in lines 173, this assumes that a systematic shift to all MLCs must exist. Please indicate based on citations or your own clinical values if this situation could occur and/or how it would be controlled or monitored.

Reply: Thanks for your comments. The purpose of this article is to discuss the sensitivity of MLC errors to PTV and OAR doses in clinical SBRT plans. Our research can help doctors and physicians recognize the relationship between MLC errors and clinical doses. Furthermore, we can provide MLC tolerance specific to SBRT as a treatment reference. According to Oliver et al., there was a linear relationship between various types of MLC errors and PTV gEUD. Table5 shows how the slope parameter from the linear fitting was used to determine the dose (gEUD) sensitivity (%/mm) to MLC position errors. The findings enable us to propose tolerances on MLC leaf positions that are dosimetrically equivalent to those considered acceptable for dose deviations in conventional therapy [2% from TG40 / TG142], at least for the target.

2. Tables in this work do not contain consistent significant digits or units of dose. Please address.

Reply: Thank you for the reminder. We have already corrected.

In Fig 3, the unit of variation for CI, GI, and D2cm is %, which has been modified in Fig 3.

In Table 1, 2, 3, and 4, the unit of the gEUD variation is %, which has been modified in the Table 1, 2, 3, and 4.

In Table 5, the dose sensitivity is in units of %/mm.

3. Do clinicians or physicists at your clinic use gEUD to make clinical decisions? How is gEUD a useful metric to monitor for QA? Please address.

Reply: Physicists at our clinic use gEUD cost functions for plan optimization, it can be an effective tool for dose sculpting in IMRT/VMAT planning. The generalized EUD can be used to evaluate dose distributions in the tumor and surrounding critical structures. It reports the generalized mean value of the non-uniform dose distribution, which represents the homogenous dose distribution that produces the same local control as that obtained with an inhomogeneous dose distribution for the case of tumors. Moreover, gEUD is closely related to normal tissue complication probability (NTCP). The gEUD is based on the radiobiologic response of the tumor rather than physical dose information, allowing it would be a better predictor of clinical outcome.

The following references provide a more detailed explanation of gEUD. (Niemierko A. Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med Phys 1997;24(1):103-10. doi:10.1118/1.598063. PMID:9029544). This literature has been cited in the article on lines 96 and 97.

4. Please indicate how random errors were simulated? No information is provided. What distribution was used to create random errors? Please cite the following paper in your discussion, as it also simulates random and systematic errors and investigates dosimetric impact: https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.12677

Reply: Thanks for your comments.

In this work, each open leaf position in each control point was modified by a number generated from a Gaussian distribution centered on zero, with a standard deviation equal to the error magnitude. Six magnitudes of random error were simulated. To avoid potential errors and unintentional duplication, we generate a new Gaussian random distribution for each error plan, so that the same errors are not added to different exposure fields and plans.

In line 74 and 75, we have provided additional explanations.

5. Specific comments:

1) Abstract:

“The aim of this study was to investigate the difference between MLC positional error and dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC).”

The usage of the word “difference” is incorrect here and meaning is not correct.

Instead: The aim of this study was to investigate the impact of MLC positional error on dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC)

Reply: Thank you for the reminder. We have already corrected it.

2) Lines 225

That all leaves would be systematically shifted by these amounts is very unlikely. The Varian Truebeam monitors leaf positions many times over per second and prevents a beam on if leaves are out of tolerance.

Reply: Thanks for your comments. In this work, regarding the dosimetric sensitivity of the PTV and OARs, we implicitly assumed that treatment plans were affected by MLC position alone(line 223). The results were based on this assumption.

3) Line 227-228

“In particular, VMAT plans have a greater impact on dose distribution than IMRT plans and should be carefully monitored”.

The authors should be more specific. The MLC positions are already closely monitored and recorded in the dynalog files. Please indicate what is meant. How specifically do reviewers plan to use these results to guide clinical QA measures? Do the authors mean IMRTQA? Is this work part of a commissioning process, determination of baseline, or educational in nature?

I am of the opinion that this study is very useful for teaching of medical physicists and demonstrating how different MLC errors can impact a patients treatment (if these errors were to not be caught by MLC control system).

Reply:Thanks for your comments. The tolerance of the MLC controller is a user-defined parameter. The optimal tolerance value is tight enough to prevent severe dosimetric changes but clinically practical enough to avoid unnecessary treatment session lengthening due to beam delivery interruptions. The purpose of this work was to evaluate the dosimetric impact of both random and systematic errors in the leaf positions of MLC, rather than to perform a retrospective study of the actual leaf position. TG-142 and ESTRO 2008 Reports recommend defining MLC positioning accuracy with qualitative weekly and quantitative monthly QA. For MLC QA, such as EPID(2D) or ArcCheck(3D) can be used for analysis to quantitatively assess MLC positioning errors, according to the results in this work, a rationalization recommendation can be made for MLC accuracy requirements to provide the accurate delivery of IMRT and VMAT.

4) Line 230

“In this study, we simulated that the MLC errors may be within a certain range.”

This sentence is not correct. Instead it should read that “in this study, we simulated MLC errors within a certain range and their dosimetric impact on SBRT plans.”

Reply: Thank you for the reminder. We have already corrected.

5) Line 231

“In future research, it would be useful to conduct experimental studies to determine the typical long term accuracy and precision of the relevant parameters for SBRT delivery”

What relevant parameters do the authors mean? This sentence is not specific. Authors need to please recognize that relevant measures that quantify dosimetric impact of MLC errors is a well-studied sub field of medical physics, so what is the authors motivation for continued monitoring?

Reply: According to the results of this paper, the dose deviations caused by errors in VMAT plans are greater than those in IMRT plans, so quality control of VMAT has received more attention and monitoring than IMRT. I agree with your assessment and recommendation. The main purpose of this research is to conduct a study of the relationship between MLC errors and clinical geud dosimetry in order to establish clinical criteria for each MLC error tolerance. The previous expression was not entirely accurate. To avoid misunderstanding, this sentence has been removed from the manuscript.

We tried our best to improve the manuscript according to the advices. And we hope that the revision will meet with your approval. Once again, thanks very much for your comments and suggestions. If you have any questions, please contact us at the following address.

Sincerely yours,

Jia Deng

Address:

Department of Radiation Oncology, Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China

Tel: +8618192331016

E-mail: dengjia92@yeah.net

Attachment

Submitted filename: 1-Response to Reviewers.docx

Decision Letter 1

Devarati Mitra

16 Nov 2022

Comparison of Dosimetric Effects of MLC Positional Errors on VMAT and IMRT plans for SBRT Radiotherapy in Non-small Cell Lung Cancer

PONE-D-22-19213R1

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Acceptance letter

Devarati Mitra

22 Nov 2022

PONE-D-22-19213R1

Comparison of Dosimetric Effects of MLC Positional Errors on VMAT and IMRT plans for SBRT Radiotherapy in Non-small Cell Lung Cancer

Dear Dr. Deng:

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: 1-Response to Reviewers.docx

    Data Availability Statement

    All minimal dataset files are available from the figshare database (accession number(s) https://doi.org/10.6084/m9.figshare.21366744.v1).


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