1

SBRT of superior liver lesions using Acuros XB calculation algorithm and 10 MV FFF
beams: a search of acceptable MLC margins
Neil Joyce, B.S., CMD, R.T.(T); Amy Herman, B.S., CMD, R.T.(T); Nathan Jones, B.S., CMD,
R.T.(R); Nishele Lenards, PhD., CMD, R.T.(R)(T), FAAMD; Ashley Hunzeker, M.S., CMD;
Matt Tobler, CMD
Medical Dosimetry Program, University of Wisconsin-La Crosse, La Crosse, WI
ABSTRACT
Dosimetric coverage to planning target volume (PTV) at the dome of the liver which
includes or abuts tissues of low densities such as lung parenchyma, can prove to be challenging.
In comparison to Acuros XB algorithm (AXB), the Analytical Anisotropic Algorithm (AAA) has
been found to be an inferior dose calculation engine, especially in areas with a high degree of
heterogeneity. Previous studies identified optimal 10 MV flattening filter-free (FFF) multi-leaf
collimator (MLC) margins in the SBRT treatment of liver lesions. To date, no studies were
specific to PTV at the dome of the liver which are associated with tissues of low densities. The
use of an advanced calculation model such as the AXB algorithm may have an impact on the
suitable MLC margins for these regions.
The aim of the current study was to determine acceptable 10 MV FFF beam MLC
margins in the stereotactic body radiation therapy (SBRT) of dome of the liver lesions using the
AXB algorithm. This research focused on 10 patients who were treated for primary liver cancer
or liver metastases located at the dome. Optimized AXB plans were analyzed to determine
acceptable MLC margins considering several plan metrics. The results support previous studies
which identified the MLC margins of -1.0 mm and 0.0 mm providing optimal normal liver tissue
sparing in addition to having the most favorable conformity index (CI) values.
Keywords: Liver SBRT, 10 MV FFF beams, AcurosXB, MLC margins, heterogeneity
Introduction
Stereotactic body radiation therapy (SBRT) for the treatment of liver cancer or liver
metastases has been shown to be safe and provide excellent outcomes.1,2 Treatment planning
goals in SBRT are to deliver the prescribed therapeutic radiation dose to the planning target
volume (PTV) and ensure rapid dose fall-off from the PTV to provide needed organs at risk
(OAR) sparing. Dosimetric coverage of PTV is essential to achieve goals of both local control
(LC) and overall survival (OS). Researchers have previously shown superior outcomes in both
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LC and OS in patients treated with liver SBRT when a biologically effective dose of 100 Gy
(BED100Gy) or more is delivered.3,4 Inherent risks of increased doses to organs at risk (OAR) are
associated with SBRT and special considerations must be made during treatment planning.5
Challenges in gaining adequate dosimetric coverage to the PTV can arise when the PTV is
surrounded by, includes, or abuts tissues of low density such as lung parenchyma.
Differing dose calculation algorithms can result in dissimilar calculated doses of both
OAR and PTV that neighbor or include tissues of low densities. Clinical implications such as
overestimation of tissues at the lung interface with the Analytical Anisotropic Algorithm (AAA)
could become a concern.6 The AAA algorithm has the tendency to overestimate the median and
mean dose to the PTV and gross tumor volume (GTV) respectively, which in turn has the
potential to directly affect clinical outcomes.7 Although the AAA algorithm is more widely used
in clinical routine, the Acuros XB algorithm (AXB) has been shown to more accurately model
dose distributions, especially in tissue with high heterogeneity such as lung parenchyma.7,8,9
As treatment facilities replace older generation linear accelerators with modern versions,
a greater number of patients will receive stereotactic radiation therapy treatments with state-of-
the-art equipment with enhanced features such as flattening filter-free (FFF) beams. The
utilization of FFF beams, when available to clinicians, has become the standard for both
stereotactic radiosurgery (SRS) and SBRT. The dramatic increased dose rate of FFF beams in
comparison to flattening filter (FF) beams enables a decrease in treatment delivery times with
reduction in OAR and PTV intra-fraction motion. Through the advent of FFF beams in radiation
therapy, benefits of both efficient treatment delivery and enhanced patient comfort were
discovered.10 Flattening filter free beams have several advantages over FF beams including an
increased dose rate factor of 2 to 4, decreased production of head scatter, and less lateral
transport due to a softer beam spectra.11 Flattening filter free beams and the effects of OAR
sparing and PTV coverage have been studied. Yan et al12 found that although PTV coverage was
similar between 10 MV FFF and FF beams, differences in OAR sparing with FFF beam was
significant for some treatment sites, such as head and neck.
When treating with SBRT, appropriate multi-leaf collimator (MLC) margins need to be
established for the intended therapy to be both safe and efficacious. The large radiation doses
intrinsic to SBRT not only have an ablative effect on tumor, but also carry potential risk of
damage to OAR. In the SBRT treatment of liver lesions, an optimal 10 MV FFF beam MLC
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margin surrounding PTV was investigated. Ogata et al13 identified suitable MLC margins in
patients treated with liver SBRT and 10 MV FFF beams, but the study was limited in that the
liver PTV did not include the dome of the liver and the AXB algorithm was not used.
To date, there has been a paucity of literature regarding appropriate MLC margins with
AXB algorithm in treatment planning in areas with high degree of tissue inhomogeneity. More
specifically, the suitable 10 MV FFF beam MLC margins using the AXB algorithm with SBRT
to dome of liver lesions are not known. The problem is the optimal MLC margin may impact
PTV coverage and OAR sparing with clinical implications.6,7 The purpose of the study was to
determine acceptable 10 MV FFF beam MLC margins in SBRT of dome of the liver lesions
using the AXB algorithm and their potential clinical effect.
Based on the known differences between algorithms, the question arises if the MLC
margins that were determined using AAA are still appropriate when using AXB. The null
hypothesis (H0) for the current study is that the AXB algorithm would have an effect on the
optimal 10 MV FFF MLC margins in areas of high tissue heterogeneity. The PTV coverage, plan
quality metrics, and OAR sparing were evaluated across multiple MLC margins and tested for
significance. For each of the dosimetric parameters evaluated, Dunn’s multiple comparison
procedure was used to compare the distributions or responses among the MLC margins. A
family-wise error rate of 5% was used for each parameter.
Methods and Materials
Patient Selection & Setup
For this single institution retrospective study, 10 patients who were treated for primary
liver cancer or liver metastases located at the dome of the liver were selected for the study. The
PTV selection criteria was limited to those with inclusion of lung after GTV expansion. The
range of lung as part of the PTV studied was 2.1% to 22.5%, with mean value of 10.6%. This
study excluded patients with PTV having < 2.0% of lung parenchyma included.
Computed tomography (CT) scans were obtained with the patient in supine orientation
with head towards the gantry and both arms above head. Treatment planning CT scans were
acquired on a General Electric LightSpeed 16 slice scanner with 2.5 mm slice thickness during
end expiratory breath-hold phase for simulation and subsequent treatment. Varian Real-Time
Position Management (RPM) system was utilized during simulation to track the patient breathing
cycle and allow gated treatment planning CT acquisition. Immobilization devices used included
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a headrest, Vac-Lok bag under the head through the hips, Civco wingboard, and a triangle
sponge under the knees with feet banded (Figure 1).
Contouring
The GTV was delineated on the treatment planning CT scan by the attending physician in
Varian Eclipse version 13.6 treatment planning system (TPS). Due to patient simulation and
treatment in end expiratory breath-hold phase, an Internal Target Volume (ITV) was not utilized.
The PTV was then generated by a GTV expansion of 1.0 cm in the superior and inferior
directions and 0.5 cm radially. Planning target volumes ranged between 7.8 cm3 and 59.4 cm3 in
the selected patient cohort. Organs at risk volumes including the liver, spinal cord, heart, lungs,
and esophagus were outlined by the planning medical dosimetrist. The liver volume was
specified as normal liver minus GTV.
Treatment Planning
All 10 patients selected for this study were planned for 5000 cGy to be delivered to the
PTV at 1000 cGy per fraction for 5 fractions. Treatment plans were created in Eclipse version
13.6 utilizing a DCA technique consisting of 6 non-coplanar arcs, with between 35° and 60°
travel range for each. A calculation grid size of 0.25 cm was used for all plans. The goals were to
create a conformal dose distribution surrounding PTV and to meet OAR dose constraints such as
normal liver dose levels, recommended by Pollom et al14, for patients receiving abdominal
SBRT. For the scope of this research, OAR analysis was limited to the liver. Flattening filter free
10 MV photon beams with dose rate of 2400 monitor units (MU) per minute were used in
planning for treatment on a Varian TrueBeam linear accelerator with 120 MLC system. Plans
were normalized such that 95% of the PTV was encompassed by the prescription dose of 5000
cGy (D95% = 5000 cGy).
Optimized DCA treatment plans using the AXB algorithm were generated to evaluate
PTV coverage, normal liver sparing, and plan quality metrics. The uniform MLC margins ranged
between -3.0 mm to 5.0 mm in 1.0 mm increments. Plan normalization was set such that 95% of
PTV received a prescription dose of 5000 cGy.
Plan Comparisons
Plan result comparisons were made between optimized AAA and AXB treatment plans
recalculated with AAA MU and tested using Wilcoxon signed rank tests (Table 1). The quality
indices and metrics used in analysis included dose received by 99% of PTV volume (D99%),
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D95%, and mean PTV dose (PTV Dmean). The AAA algorithm was confirmed to overestimate
PTV doses as observed in previous studies.7,8,9
Optimized AXB plan metrics used in analysis included PTV D99%, PTV Dmean,
homogeneity index (HI) defined as dose received by 5% of volume (D5%) divided by D95%,
Radiation Therapy Oncology Group (RTOG) conformity index (CIRTOG) defined as prescription
isodose volume (PIV) divided by target volume (TV), gradient index (GI) defined as half
prescription isodose volume (PIVhalf) divided by PIV, mean liver dose (liver Dmean), and volume
of liver receiving 2000 cGy or more (liver V20Gy). Conformity index is an important tool to
assess the degree of how well a planned dose distribution conforms to the PTV with favorable CI
values limiting dose to surrounding normal tissues. As defined by the RTOG, normal CIRTOG
value range is 1 - 2, with major deviation greater than 2.5. Optimal HI values are observed when
at or near 1, an indication of ideal dose homogeneity. The GI is used as a tool to compare
treatment plans with similar conformity, but with variance in dose gradients. Plans with lower GI
values indicate a steeper dose gradient as compared to plans with higher GI values and
subsequently indicate greater normal tissue sparing.
Statistical Analysis
For each of the dosimetric parameters evaluated with optimized AXB plans, Dunn’s
multiple comparison procedure was used to compare the distributions or responses among the
MLC margins with a family-wise error rate of 5% used for each parameter. The p-values of
>0.05 were considered not significantly different from the optimal value in the population. For
optimized AAA and AXB treatment plans, Wilcoxon signed rank tests were performed at each
MLC margin level to allow comparison of dose distributions. The Benjamini-Hochberg
adjustment was made for each parameter with a family-wise error rate of 5% to control Type 1
error rate for multiple testing over the 9 MLC margins studied. Wilcoxon signed rank tests were
used rather than paired t-tests due to small sample sizes and non-normality observed in some of
the data samples. P-values of < 0.05 were considered to be statistically significant. All statistical
analyses were performed using R (R Core Team, 2019).
Results
PTV
The PTV D99% and PTV Dmean results displayed a quadratic trend with increasing MLC
margins (Figure 2). The minimum mean PTV D99% was found to be 3834 cGy (σ 132.18) with -
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3.0 mm MLC margins, with maximum of 4824 cGy (σ 66.028) observed with 5.0 mm MLC
margins. In comparison to the PTV D99%, an inverse relationship was revealed with the PTV
Dmean metric (Figure 3). The maximum mean PTV Dmean was 8408 cGy (σ 575.47) with -3.0 mm
MLC margins and minimum mean PTV Dmean of 5416 cGy (σ 69.98) delivered with 5.0 mm
margins (Table 2). The null hypothesis was rejected due to the quadratic relationships of PTV
metrics and MLC margins.
Plan Quality
The HI values were found to increase quadratically with decreasing MLC margins
(Figure 4). The mean HI was the least with 5.0 mm MLC margins at 1.15 (σ 0.028) with -3.0
MLC margins resulting in the highest mean HI value of 2.16 (σ 0.252). The lowest mean CI was
found to be 1.18 (σ 0.096) with 0.0 mm MLC margins in optimized AXB plans (Figure 5).
Gradient index values generally increased with MLC margin (Figure 6). The minimum mean GI
of 2.99 (σ 0.025) was found to be as a result of -2.0 mm margins and maximum of 3.83 (σ 0.540)
with 5.0 mm margins. Similar to the PTV analysis, the null hypothesis was rejected due to the
quadratic nature of the relationship between the MLC margins and both HI and GI data. The CI
analysis indicated rejection of the null hypothesis due to the similarities observed in comparison
to results of previous studies.13
Liver
The mean liver Dmean across all MLC margins was found to be 589 cGy (Table 3). In the
optimized AXB plans studied, the mean liver Dmean values were the least with 541 cGy (σ
286.729) using 0.0 mm margins and 547 cGy (σ 291.423) with -1.0 mm MLC margins. The
highest mean liver Dmean of 669 cGy (σ 334.961) was observed with 5.0 mm margins (Figure 7).
In terms of the mean liver V20Gy, a quadratic trend was observed between 0.0 mm and 5.0
mm MLC margins (Figure 8). The minimum mean liver V20Gy of 83.2 cm3 (σ 43.753) and 83.3
cm3 (σ 44.143) was delivered with 0.0 mm and -1.0 mm MLC margins respectively. Upon
analysis of normal liver metrics in correspondence with previous studies13, the null hypothesis
was once again rejected.
Discussion
In this study, the optimal 10MV FFF beam MLC margins for PTV at the dome of the
liver were investigated. The PTV D99%, PTV Dmean, and HI were found to follow a quadratic
trend among MLC margins studied. Given the direct relationship between MLC margins and
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PTV metrics, 5.0 mm MLC margins resulted in the highest mean PTV D99% and least mean PTV
Dmean. The -3.0 mm MLC margins produced the lowest mean PTV D99% and the highest mean
PTV Dmean. Upon analysis of all parameters, the PTV metrics as observed with -1.0 mm and 0.0
mm MLC margins were found to be an acceptable balance between the results found. The
optimal CI results were observed with 0.0 mm (1.18), and -1.0 mm (1.20) MLC margins. In
addition, -2.0 mm and -1.0 mm MLC margins provided the most favorable mean GI results with
2.99 and 3.01 respectively. Both the mean liver Dmean and mean liver V20Gy results were the least
with 0.0 mm, and -1.0 mm MLC margins.
Given the known differences between the AAA and AXB algorithms in regions of high
heterogeneity, an impact on the optimal MLC margins utilizing AXB was expected. In the
limited number of patients selected for this study, the mean amount of lung included as part of
the PTV studied was 10.6%. In cases with greater PTV expansion or larger GTV which would
intrinsically cause more involvement with the lung parenchyma, the disparities between
algorithms may become more apparent.
The studies performed by Ogata13 et al and Cardinale15 et al were important in
establishing guidelines in reference to which MLC margin resulted in optimal PTV and OAR
results when planning SBRT of the liver. Both studies were performed using algorithms with
limited dose model capabilities, with the potential to impact the appropriate MLC margins
needed to provide optimal PTV and OAR treatment plan results. The current research findings
were analogous to those found by Ogata et al13 and Cardinale et al15 in studying optimal MLC
margins in SBRT liver treatment. Ogata et al13 concluded the MLC margins of 0.0 mm and -1.0
mm were found to provide optimal CI, GI, and liver tissue sparing. In the Cardinale15 study, the
results showed plans with a 0.0 mm MLC margin proved to provide the best liver sparing. The
statistical testing of the optimal MLC margins exhibited non-significance between the MLC
margins as observed in CI, liver Dmean, and liver V20Gy metrics. However, during plan evaluation
the clinician would likely select the plan which would provide the optimal conformity and
maximum OAR dose reduction.
Conclusion
Stereotactic body radiotherapy has been shown be safe and effective in the management
of primary liver cancers and liver metastases.1,2 Flattening filter free beams are favored in SBRT
because of the dramatic dose rate increase over FF beams which leads to decreased intra-fraction
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motion and increased patient comfort with less time spent on the treatment table. Advanced
calculation algorithms such as AXB have been shown to better model radiation doses as
compared to AAA algorithm, particularly in regions with a high degree of tissue inhomogeneities
such as the dome of liver.8,9 The current study as suggested by Rana16, displayed an over-
estimation of PTV doses by the AAA algorithm in areas with tissues of a high degree of
heterogeneity.
The purpose of the current study is to determine acceptable 10 MV FFF beam MLC
margins in the SBRT of dome of the liver lesions using the AXB algorithm. While evaluating
effects of various uniform MLC margins using 10 MV FFF beams utilizing AXB algorithm in
SBRT of superior liver lesions near the dome, acceptable MLC margins were found to be -1.0
mm and 0.0 mm. The current research findings mirror the results of Ogata et al13 identifying
suitable FFF beam MLC margins in liver SBRT. The introduction of the AXB algorithm coupled
with plans with heterogenous PTV at the dome of the liver resulted in no difference in optimal
SBRT 10MV FFF MLC margins, with results of study rejecting the null hypothesis.
A limitation of this study was the wide range of PTV sizes and variance in the amount of
lung tissue included in them. The small population sample size was due to the limited number of
patients in the department which fit the study criteria. Further studies are needed to describe the
effects of both PTV size and amount of lung inclusion in PTV on the optimal FFF beam MLC
margins using AXB algorithm. The results found in this study may be further refined by
implementing asymmetric MLC margins.
Acknowledgements
The authors would like to thank Dr. David Reineke of the UW-La Crosse Statistical
Consulting Center for his assistance in statistical analysis and interpretation of statistical results
of the study.
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7. Padmanaban S, Warren S, Walsh A, Partridge M, Hawkins MA. Comparisons of Acuros
(AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of
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2014;9:286. http://dx.doi.org/10.1186/s13014-014-0286-3
8. Chopra KL, Leo P, Kabat C, et al. Evaluation of dose calculation accuracy of treatment
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9. Fogliata A, Nicolini G, Clivio A, et al. Dosimetric evaluation of Acuros XB advanced dose
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http://dx.doi.org/10.4103/0971-6203.139003
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11. Sharma SD. Unflattened photon beams from the standard flattening filter free accelerators for
radiotherapy: Advantages, limitations and challenges. J Med Phys. 2011;36(3):123-125.
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12. Yan Y, Yadav P, Bassetti M, et al. Dosimetric differences in flattened and flattening filter-
free beam treatment plans. J Med Phys. 2016;41(2):92-99. http://dx.doi.org/10.4103/0971-
6203.181636
13. Ogata T, Nishimura H, Mayahara H, Uehara K, Okayama T. Identification of the suitable
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abdominal and thoracic stereotactic body radiotherapy. Semin Radiat Oncol.
2017;27(3):197-208. http://dx.doi.org/10.1016/j.semradonc.2017.02.001
15. Cardinale RM, Wu Q, Benedict SH, et al. Determining the optimal block margin on the
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Phys. 1999;45(2):515-520. http://dx.doi.org/10.1016/S0360-3016(99)00203-5
16. Rana S. Clinical dosimetric impact of Acuros XB and analytical anisotropic algorithm
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2014;2(1):02019. http://dx.doi.org/10.14319/ijcto.0201.9
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Figures

Figure 1. Patient position and immobilization for CT simulation and treatment.

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Figure 2. Optimized AXB plan mean PTV D99% (cGy) all MLC margins.
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Figure 3. Optimized AXB plan mean PTV Dmean (cGy) across all MLC margins.
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Figure 4. Optimized AXB plan mean HI across all MLC margins.

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Figure 5. Optimized AXB plan mean CI across all MLC margins.

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Figure 6. Optimized AXB plan mean GI across all MLC margins.

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Figure 7. Optimized AXB plan mean liver Dmean (cGy) across all MLC margins.
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Figure 8. Optimized AXB plan mean liver V20Gy (cm3) across all MLC margins.
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Tables

Table 1. Comparison between AAA and AXB plans using preset monitor units from the AAA plans across all uniform MLC
margins.
MLC margin (mm) -3 -2 -1 0 1 2 3 4 5 Mean
Mean PTV D99% (cGy)
Optimized AAA 3769.6 4015.1 4298 4529.4 4656.4 4727.1 4768.2 4805.2 4827.5 4488.5
AXB Preset AAA MU 3821.0 3985.9 4197.4 4403.8 4551.6 4656.6 4715.9 4774.1 4809.1 4435.0
p-value* 0.025 0.006 0.006 0.006 0.021 0.037 0.063 0.322 0.636
Mean PTV D95% (cGy)
Optimized AAA 5000 5000 5000 5000 5000 5000 5000 5000 5000 5000
AXB Preset AAA MU 4981.2 4918.3 4892.4 4911.2 4933.5 4965.3 4984.0 4996.6 4999.5 4953.6
p-value* 0.233 0.006 0.006 0.006 0.029 0.151 0.555 1.000 1.000
Mean PTV Dmean (cGy)
Optimized AAA 8447.9 7288.6 6549.8 6027.2 5741.8 5618.6 5541.3 5480.9 5441.3 6237.5
AXB Preset AAA MU 8386.8 7235.5 6504.6 6007.4 5741.2 5600.2 5524.4 5463.6 5421.3 6209.4
p-value* 0.012 0.012 0.012 0.119 0.160 0.108 0.108 0.108 0.108
*FDR-adjusted
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Table 2. Response means by MLC margin.

MLC Margin (mm)
Response -3 -2 -1 0 1 2 3 4 5
CI 1.44 1.29 a 1.20 a 1.18* 1.20 a 1.26 a 1.32 1.39 1.48
Liver Dmean (cGy) 608.7 a 570.4 a 546.8 a 540.6* 554.3 a 578.2 a 604.0 a 636.4 a 669.3a
Liver V20Gy (cm3) 94.8 a 87.4 a 83.3 a 83.2* 86.9 a 92.6 a 98.8 a 106.8 a 115.1
GI 3.02 a 2.99* 3.01 a 3.09 a 3.22 a 3.36 3.50 3.71 3.83
PTV D99% (cGy) 3834 4055 4302 4497 4623 4703 a 4747 a 4794 a 4824*
HI 2.16 1.77 1.53 1.36 1.27 1.21 a 1.18 a 1.16 a 1.15*
PTV Dmean (cGy) 8408* 7339 a 6624 a 6095 5809 5631 5533 5460 5416
The green cells represents the optimal level and the yellow shading is for MLC levels that are not
significantly different from the optimal for that response variable.
* Optimal value in the sample
a
Not significantly different from the optimal value in the population (P > 0.05)
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Table 3. AXB plan results across all uniform MLC margins studied.
MLC margin (mm) -3 -2 -1 0 1 2 3 4 5 Mean

Mean PTV D99% (cGy) 3834.3 4055.1 4302.5 4496.7 4622.8 4702.8 4747 4794.2 4823.6 4486.6
SD 132.184 117.728 69.971 76.735 87.693 90.194 82.759 73.579 66.028

Mean PTV Dmean (Gy) 8407.8 7339.1 6623.6 6094.5 5808.9 5631.2 5533.5 5460.4 5415.7 6257.2
SD 575.467 264.167 149.278 91.339 71.186 69.706 66.230 70.314 69.981

Mean HI (cm3) 2.16 1.77 1.53 1.36 1.27 1.21 1.18 1.16 1.15 1.4
SD 0.252 0.116 0.066 0.039 0.030 0.028 0.028 0.028 0.028

Mean CI 1.44 1.29 1.20 1.18 1.20 1.26 1.32 1.39 1.48 1.3
SD 0.207 0.129 0.091 0.096 0.107 0.122 0.146 0.163 0.185

Mean GI 3.02 2.99 3.01 3.09 3.22 3.36 3.50 3.71 3.83 3.3
SD 0.225 0.246 0.249 0.230 0.255 0.333 0.425 0.574 0.540

Mean Liver Dmean (cGy) 608.7 570.4 546.8 540.6 554.3 578.2 604.0 636.4 669.3 589.9
SD 313.878 302.593 291.423 286.729 290.549 300.558 309.430 323.091 334.961

Mean Liver V20Gy (cm3) 94.8 87.4 83.3 83.2 86.9 92.6 98.8 106.8 115.1 94.3
SD 47.293 45.704 44.143 43.753 45.056 47.542 49.653 53.050 56.107