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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); Ashley Hunzeker, M.S., CMD; Nishele Lenards, PhD., CMD, R.T.(R)(T), FAAMD;
Matt Tobler, CMD
Medical Dosimetry Program, University of Wisconsin-La Crosse, La Crosse, WI
ABSTRACT
Keywords:
Introduction
Stereotactic body radiation therapy (SBRT) in 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 of paramount importance to achieve goals of
both local control (LC) and overall survival (OS). Researchers have previously shown superior
outcomes in both LC and OS in patients treated with liver SBRT when a biologically effective
dose of 100 Gy or more is delivered (BED100Gy).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, including, or abuts tissues of low density such as lung parenchyma.
Differing dose calculation algorithms can result in dissimilar calculated doses of both
OAR and PTVs that neighbor or include tissues of low densities and can have the potential to
make a clinical impact.6 Although the Analytical Anisotropic Algorithm (AAA) is more widely
used in clinical routine, 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
Furthermore, AAA 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 Cakir10 studied dosimetric plan results with 10 MV flattening filter free (FFF) beams
using AAA and AXB calculation algorithms in the treatment of liver lesions and the effect of
calculation grid size (CGS), which showed no significant differences between PTV doses
calculated with AXB 1.0 mm CGS and AXB with 2.5 mm CGS. Cakir’s study was limited in
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that it was not specific to liver PTVs located near the liver dome and lung tissue interface. 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 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.11 Flattening filter free beams have several advantages over FF beams including an
increased dose rate factor of 2 - 4, decreased production of head scatter, and less lateral transport
due to a softer beam spectra.12 Flattening filter free beams and the effects of OAR sparing and
PTV coverage have been studied. Yan et al13 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.
When treating with SBRT, appropriate 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 multi-leaf collimator (MLC)
margin surrounding PTV was investigated. A study performed by Ogata et al 14 identified the
suitable MLC margins in patients treated with liver SBRT and 10 MV FFF beams. The liver
PTVs studied were not explicitly reported to be located at the dome of the liver. The Ogata et al 14
study was limited in that an advanced calculation algorithm such as AXB was not employed, as
PTV coverage challenges arise in SBRT planning when PTV is associated with tissues of low
densities.15 The presence of heterogenous tissues included in PTVs at the liver dome may have
an impact on the acceptable MLC margins necessary to produce favorable treatment planning
results. The current study was two-fold by design. The primary goal was to find acceptable 10
MV FFF beam MLC margins in SBRT of liver PTVs at the dome of the liver utilizing an
algorithm with superior dose modeling capabilities. Second, the impact on PTV and liver metrics
was studied with comparisons made between the use of AAA and AXB algorithms when
planning involves PTVs associated with tissues of high heterogeneity.
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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 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 PTVs studied was 2.1% to 22.5%, with mean value of 10.6%. This study
excluded patients with PTVs having < 2% of lung parenchyma involvement.
Computed tomography 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), Varian Medical Systems, Palo Alto, CA] system was utilized
during simulation to track patient breathing cycle and allow gated treatment planning CT
acquisition. Immobilization devices used included a headrest, Vac-Lok bag under the head
through hips, wingboard (Civco, Coralville, IA), 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
Eclipse (Varian Medical Systems, Palo Alto, CA) version 13.6 treatment planning system. 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. 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 50 Gy to be delivered to the PTV
at 10 Gy per fraction for 5 fractions. Treatment plans were created in Eclipse treatment planning
system (TPS) utilizing a dynamic conformal arc (DCA) technique consisting of 6 non-coplanar
arcs, with each arc travel range between 35° to 60°. 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
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meet OAR dose constraints such as normal liver dose levels recommended by Pollom et al 16 for
patients receiving abdominal SBRT. For this retrospective study, OAR analysis was limited to
the liver. Flattening filter free 10 MV photon beams with dose rate of 2400 monitor units (MUs)
per minute were used in planning for treatment on a TrueBeam (Varian Medical Systems, Palo
Alto, CA) linear accelerator with 120 MLC system. Plans were normalized such that 95% of the
PTV was encompassed by the prescription dose of 50 Gy (D95% = 50 Gy).
Optimized DCA treatment plans using AAA and AXB algorithms were generated to
allow comparison between these algorithms in terms of PTV, normal liver, and plan quality
metrics. The uniform MLC margins used for both sets of plans ranged between -3.0 mm to 5.0
mm in 1.0 mm increments. Plan normalization for both algorithms was set such that 95% of PTV
received a prescription dose of 50 Gy.
Subsequently, the optimized AAA plans were recalculated with the AXB algorithm.
These plans used preset MUs from optimized AAA plans with no plan normalization assigned.
The results from the recalculated preset AXB plans were compared to those of the optimized
AAA plans to evaluate differences in PTV metrics due to the use of independent algorithms.
Lastly, optimized AXB plans were further analyzed to identify acceptable MLC margins.
Plan Comparisons
Plan result comparisons were made between the optimized AAA and AXB treatment
plans to evaluate differences between them using various quality indices. Metrics used in
analysis included dose received by 99% of PTV volume (D99%), D95%, mean PTV dose,
homogeneity index (HI) defined as dose received by 5% of volume (D 5%) divided by D95%,
Radiation Therapy Oncology Group (RTOG) conformity index (CI RTOG) 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 20 Gy or more (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 CI RTOG 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
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indicate a steeper dose gradient as compared to plans with higher GI values and subsequently
indicate greater normal tissue sparing.
Planning target volume doses were examined between the optimized AAA plans and
AXB plans recalculated with preset MUs from AAA plans. Dose received by 99% of PTV
volume (D99%), D95%, and mean PTV dose were compared between plans to identify disparities
between them. Finally, optimized AXB plans were analyzed to identify acceptable MLC
margins using plan quality metrics including PTV D 99%, mean PTV dose, HI, CI, GI, liver Dmean,
and liver V20Gy.
Statistical Analysis
For all dosimetric parameters evaluated, Wilcoxon signed rank tests were performed at
each MLC margin level to allow comparison of dose distributions between the optimized AAA
and AXB treatment plans. 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. Statistical analysis was performed using R (R Core Team, 2019).
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.
Results
The optimized AAA and AXB treatment plans presented similar results in terms of both
PTV and liver doses. The mean PTV D99% for AAA plans was found to be 44.89 Gy, with mean
PTV D99% 44.87 Gy for AXB plans (Table 1). All PTV D99% comparison results were
statistically insignificant, with the exception of -3.0 mm and -2.0 mm MLC margins (p=0.018).
Mean PTV doses were also found to be comparable between the optimized AAA and AXB
plans, with doses of 62.38 Gy for the former and 62.57 Gy for the latter (Table 2). Significance
was observed between -3.0 mm (p=0.049) and 1.0 mm (p=0.029) MLC margins. Mean HI, CI,
and GI of AAA and AXB plans were found to identical. Calculations of HI, CI, and GI between
all MLC margins for each algorithm studied were found to be 1.4, 1.3, and 3.3 respectively
(Tables 3-5). Relevant differences were observed in HI between -2.0 mm (p=0.039) and 0.0 mm
(p=0.039) MLC margins only. Both CI and GI comparisons resulted in no statistical significance
between the optimized AAA and optimized AXB plans. Liver mean dose was overestimated with
the AAA algorithm. The mean liver Dmean for the AAA plans was found to be 5.95 Gy, with 5.89
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Gy mean liver Dmean for AXB plans (Table 6). Plans with -3.0 mm (p=0.018) and 2.0 mm
through 5.0 mm (p=0.018) margins resulted in statistical significance when compared. The
results of liver V20Gy displayed similar doses received between both algorithms. The mean liver
V20Gy doses for AAA and AXB plans were 5.95 Gy and 5.89 Gy respectively (Table 7). Three-
millimeter (p=0.022), 2.0 mm (p=0.088), and 3.0 mm through 5.0 mm (p=0.022) MLC margins
tested as significant results.
Results of plans recalculated with AXB algorithm with AAA plan MUs showed lower
doses received to PTV in all metrics studied (Tables 8-10). Planning target volume D 95% was
prescribed to 50 Gy in the AAA plans and was found to be 49.45 Gy in the plans recalculated
with AXB. Statistical significance was observed between -2.0 mm (p=0.006) and 1.0 mm
(p=0.029) MLC margins. The mean PTV D99% in the AAA plans was 44.89 Gy with the mean
PTV D99% found to be 44.35 Gy in the recalculated plans with AXB. Significance was noted
between -3.0 mm (p=0.025) and 2.0 mm (p=0.037) MLC margins. Mean PTV D mean doses for
the optimized AAA plans and those recalculated with AXB algorithm were 62.38 Gy and 62.09
Gy respectively, with MLC margins between -3.0 mm (p=0.012) and -1.0 mm (p=0.012) found
to be significant.
Optimized AXB treatment plans with various MLC margins results were analyzed. The
PTV D99%, PTV Dmean, and HI results displayed a linear trend with increasing MLC margins
(Figures 2-4). The minimum D99% was with -3.0 mm MLC margins (38.34 Gy) and was most
with 5.0 mm MLC margins (48.24 Gy). The PTV Dmean maximum dose was found with -3.0 mm
margins (84.08 Gy), and minimum PTV Dmean was with 5.0 mm margins (54.16 Gy). The lowest
HI value was demonstrated with 5.0 mm MLC margins (1.15) with the highest HI value found as
a result of -3.0 MLC margins (2.16). The conformity index results showed optimal values to
range between -1 mm margins (1.2), 0.0 mm margin (1.18) and 1.0 mm margins (1.2) (Figure 5).
Gradient index values generally increased with MLC margin (Figure 6). The minimum GI was
found to be as a result of -2.0 mm margins (2.99) and maximum GI with 5.0 mm margins (3.83).
Optimal liver mean dose values were seen with -1.0 mm margin (5.47 Gy) and 0.0 mm margin
(5.41 Gy) (Figure 7). The lowest liver Dmean was found with using 0 mm margins (5.41 Gy), with
the use of 5.0 mm margins yielding the highest liver D mean of 6.69 Gy. In addition, 0.0 mm and -
1.0 mm MLC margins yielded the least liver V20Gy doses (Figure 8).
Discussion
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The primary goal of this study was to determine acceptable 10 MV FFF beam MLC
margins in SBRT of the dome of the liver. Treatment plans were developed using MLC margins
ranging from -3.0 mm to 5.0 mm surrounding the PTV utilizing AXB algorithm. Subsequent
data analysis was performed to identify acceptable MLC margins considering several plan
quality indices. The results displayed optimal MLC margins of 0.0 mm and -1.0 mm as observed
across CI, GI, liver Dmean, and liver V20Gy metrics. The HI increased from 1.36 in plans with 0.0
mm margin to 1.53 with -1.0 mm margin, as a trend across all plans showed an increase in HI as
smaller MLC margins were used. Plans using -1.0 mm and 0.0 mm MLC margins yielded the
lowest liver Dmean doses values of 5.47 Gy and 5.41 Gy respectively. Planning target volume
D99% results were also better with MLC margin of 0.0 mm (44.97 Gy) when compared to 43.03
Gy with -1.0 mm MLC margin. The findings of this study were analogous to those found by
Ogata et al14 and Cardinale et al17 in studying optimal MLC margins in SBRT liver treatment.
Ogata et al14 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 Cardinale17 study, the results showed plans with a 0.0 mm
MLC margin proved to provide the best liver sparing. The studies performed by Ogata et al and
Cardinale 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 of these studies
were performed using algorithms with limited dose model capabilities, which may impact the
appropriate MLC margins needed to provide optimal PTV and OAR treatment plan results.
The results of AAA plans recalculated with AXB using AAA MUs showed that AAA
algorithm overestimated doses to PTV at the dome of liver. In addition, larger liver D mean doses
were shown in plans calculated with AAA algorithm in comparison to results from those
calculated with AXB using AAA MUs. Planning target volumes at the dome of the liver included
a section of lung parenchyma, a tissue with a high degree of heterogeneity. The plans calculated
with AXB provided a more realistic dose model in these areas as demonstrated in other
studies.7,8,9 The higher PTV doses seen in plans calculated with AAA in comparison to those
calculated with AXB are consistent with previous observations by Padmanaban et al. 7 The
limitations of AAA algorithm were observed in the overestimation of PTV doses when
comparing AAA plans with those recalculated with AXB using AAA MUs.
Conclusion
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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
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 high degree of tissue inhomogeneities
such as the dome of liver.7
In the current research evaluating effects of various 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 0.0 mm and -1.0 mm. These findings mirror the results of Ogata
et al14 and their identification of suitable FFF beam MLC margins in liver SBRT. The focus of
the current plan study was dome of liver PTVs with lung inclusion. The results were found to be
analogous to those observed by Ogata et al 14, whose study was not specific to dome of liver
PTVs. Plans with MLC margins of 0.0 mm and -1.0 mm provided optimal normal liver tissue
sparing in addition to having the most favorable CI and GI values. Dose received by 99% of the
PTV was slightly less for -1.0 mm MLC margins in comparison to 0.0 mm MLC margins. Both
HI and mean PTV dose values increased linearly as MLC margins were decreased. The results of
plans using AXB in comparison to AAA demonstrated more representative doses in regions of
tissues with high degrees of heterogeneity as demonstrated in previous studies. 7,8,9 The AXB
algorithm is indicated for dose calculations when PTVs include tissues of high degree of
heterogeneity as suggested by Rana.15 A limitation of this study is the wide range of PTV sizes
and variance in the amount of lung tissue included in them. 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.
Acknowledgements
The authors would like to thank Dr. David Reineke of the UWL 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
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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.

Figure 2. A linear plot displaying an optimized AXB plan mean PTV D 99% (cGy) all MLC
margins.
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Figure 3. A linear plot displaying an optimized AXB plan mean PTV D mean (cGy) across all
MLC margins.

Figure 4. A linear plot displaying an optimized AXB plan mean HI across all MLC margins.
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Figure 5. A linear plot displaying an optimized AXB plan mean CI across all MLC margins.

Figure 6. A linear plot displaying an optimized AXB plan mean GI across all MLC margins.
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Figure 7. A linear plot displaying an optimized AXB plan mean liver D mean (cGy) across all
MLC margins.

Figure 8. A linear plot displaying an optimized AXB plan mean liver V 20Gy (cm3) across all
MLC margins.
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Tables

Tables 1-7. Comparison between AAA and AXB plans across all MLC margins studied.
Tables 8-10. Comparison between AAA and AXB plans using preset monitor units from the AAA plans across all MLC margins.

MLC margin (mm) -3 -2 -1 0 1 2 3 4 5


Table 1. Mean PTV D99% (cGy)
Optimized AAA 3769.6 4015.1 4298 4529.4 4656.4 4727.1 4768.2 4805.2 4827.5
Optimized AXB 3834.3 4055.1 4302.5 4496.7 4622.8 4702.8 4747 4794.2 4823.6
p-value* 0.018 0.018 0.486 0.151 0.151 0.158 0.151 0.206 0.625
Table 2. Mean PTV Dmean (cGy)
Optimized AAA 8447.9 7288.6 6549.8 6027.2 5741.8 5618.6 5541.3 5480.9 5441.3
Optimized AXB 8407.8 7339.1 6623.6 6094.5 5808.9 5631.2 5533.5 5460.4 5415.7
p-value* 0.049 0.056 0.026 0.026 0.029 0.557 0.180 0.063 0.049
Table 3. Mean HI
Optimized AAA 2.16 1.75 1.51 1.35 1.26 1.22 1.19 1.17 1.16
Optimized AXB 2.16 1.77 1.53 1.36 1.27 1.21 1.18 1.16 1.15
p-value* 0.184 0.039 0.039 0.039 0.135 0.595 0.726 0.595 0.135
Table 4. Mean CI
Optimized AAA 1.45 1.28 1.19 1.17 1.20 1.27 1.35 1.42 1.51
Optimized AXB 1.44 1.29 1.20 1.18 1.20 1.26 1.32 1.39 1.48
p-value* 0.191 0.169 0.168 0.191 0.282 0.169 0.168 0.169 0.171
Table 5. Mean GI
Optimized AAA 3.06 3.00 3.03 3.11 3.22 3.36 3.48 3.66 3.78
Optimized AXB 3.02 2.99 3.01 3.09 3.22 3.36 3.50 3.71 3.83
p-value* 0.123 .0316 0.738 0.846 0.846 0.804 0.360 0.496 0.123
Table 6. Mean Liver Dmean (cGy)
Optimized AAA 617.0 572.0 545.8 540.3 556.8 584.3 612.3 646.3 679.8
Optimized AXB 608.7 570.4 546.8 540.6 554.3 578.2 604.0 636.4 669.3
p-value* 0.018 0.646 0.363 0.363 0.363 0.018 0.018 0.018 0.018
Table 7. Mean Liver V20Gy (cm3)
Optimized AAA 96.8 87.8 83.2 83.2 87.4 93.8 100.5 108.9 117.4
Optimized AXB 84.8 87.4 83.3 83.2 86.9 92.6 98.8 106.8 115.1
p-value* 0.022 0.866 0.482 0.482 1.000 0.088 0.022 0.022 0.022
Table 8. Mean PTV D99% (cGy)
Optimized AAA 3769.6 4015.1 4298 4529.4 4656.4 4727.1 4768.2 4805.2 4827.5
Preset AXB MU 3821.0 3985.9 4197.4 4403.8 4551.6 4656.6 4715.9 4774.1 4809.1
p-value* 0.025 0.006 0.006 0.006 0.021 0.037 0.063 0.322 0.636
Table 9. Mean PTV D95% (cGy)
Optimized AAA 5000 5000 5000 5000 5000 5000 5000 5000 5000
Preset AXB MU 4981.2 4918.3 4892.4 4911.2 4933.5 4965.3 4984.0 4996.6 4999.5
p-value* 0.233 0.006 0.006 0.006 0.029 0.151 0.555 1.000 1.000
Table 10. Mean PTV Dmean (cGy)
Optimized AAA 8447.9 7288.6 6549.8 6027.2 5741.8 5618.6 5541.3 5480.9 5441.3
Preset AXB MU 8386.8 7235.5 6504.6 6007.4 5741.2 5600.2 5524.4 5463.6 5421.3
p-value* 0.012 0.012 0.012 0.119 0.160 0.108 0.108 0.108 0.108
*FDR-adjusted